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List of Clinical Trials


The list of Clinical Trials set forth here are primarily third party studies not funded by L-Nutra (other than the supply of FMD) evaluating the safety and efficacy of Fasting Mimicking Technology for various health issues. FMD has not been shown to be safe and effective for use in disease populations and ongoing research into these uses should not be taken to mean such use has received regulatory approval. Do not use FMD to self-treat for any diseases identified in this list of clinical trials.

1. Title: Safety, Feasibility and Metabolic Effects of the Fasting Mimicking Diet (FMD) in Cancer Patients

Status: Completed
Participants: FMD in cancer patients; 85 participants
Study: Interventional, Single Group Assignment (February 1, 2017 – March 30, 2019); Estimated Study Completion Date: April 30, 2019
Location: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Researcher: Prof. Filippo De Braud (filippo.debraud@istitutotumori.mi.it); Claudio; Claudio Vernieri, MD, PhD (claudio.vernieri@ifom.eu)

Synopsis: In preclinical studies, cyclic calorie-restricted diets reduce the risk of several cancers and improve the antitumor activity of standard treatments against already established malignancies. In particular, the fasting mimicking diet (FMD), a plant-based, calorie-restricted, low carbohydrate, low-protein diet to be repeated cyclically every 3-4 weeks, enhances the antitumor activity of cytotoxic chemotherapy, while contemporarily protecting healthy tissues and stimulating antitumor immunity. Most of these effects are likely mediated by the reduction of blood glycemia and growth factors, such as insulin and insulin-like growth factor 1 (IGF-1). When administered to healthy volunteers, cyclic FMD has been shown to be safe and capable of reducing risk factors for different chronic diseases. However, the effects of the FMD in cancer patient populations have not been evaluated so far. This study aims to assess the safety, feasibility and metabolic effects of the FMD in cancer patients treated with different standard antitumor therapies. Patients with any malignancy, with the exception of small cell neuroendocrine tumors, will be considered for enrollment in this study. The FMD will be administered up to a maximum of 8 consecutive cycles in combination with standard adjuvant treatments or therapies for advanced disease.

Trial registration: ClinicalTrials.gov -- NCT03340935

2. Title: Impact of Dietary Intervention on Tumor Immunity -- The DIgesT Trial

Status: Ongoing
Participants: FMD in breast cancer and melanoma; 100 participants
Study: Interventional, Single Group Assignment (July 1, 2018 - May 30, 2020); Estimated Study Completion Date: December 31, 2020
Location: Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
Researcher: Prof. Filippo De Braud (filippo.debraud@istitutotumori.mi.it); Claudio Vernieri, MD, PhD (claudio.vernieri@ifom.eu)

Synopsis: Preclinical evidences suggest that reducing the concentration of blood metabolites and growth factors reduces the in vivo growth of several tumor models, while protecting normal tissues from the cytotoxic effects of chemotherapeutical treatments. In recent years, a plant-based, calorie-restricted, low-carbohydrate, low-protein diet, also known as Fasting Mimicking Diet (FMD), has been proposed as a potential anticancer dietary intervention. The FMD is safe when administered cyclically (every 21-28 days) to healthy volunteers, and is capable of significantly reducing the concentration of plasma glucose, serum insulin and IGF-1, while increasing levels of plasma IGFBPs and ketone bodies. The FMD has been shown to inhibit the in vivo growth of several tumor models, including breast cancer and melanoma mice models. The anticancer effects of the FMD are likely mediated by two concomitant mechanisms: 1) one direct anticancer effect that is mediated by the inhibition of energy production and anabolic pathways, such as protein and fatty acid synthesis, in cancer cells; 2) one indirect effect that is mediated by the activation of antitumor immunity, with the result of enhanced tumor infiltration by cytotoxic CD8+ T-lymphocytes and reduced infiltration by immunosuppressive populations. According to the currently accepted model, the anticancer and immunomodulatory effects of the FMD mostly derive from the reduction of circulating glucose, insulin and IGF-1 levels, and a parallel increase of ketone body and IGF-1 binding protein concentration. However, recent observations in healthy volunteers and cancer patients, suggest that FMD-mediated changes in many other metabolites, such as specific amino acids or fatty acids, could contribute to the cell-autonomous or immune-mediated anticancer effects of the FMD. While the study of the effects of the FMD in combination with standard treatments (e.g. chemotherapy, molecular targeted therapy) in advanced cancers represents the final objective of the ongoing studies, fully uncovering the metabolic and immunological effects of the FMD alone is essential to design future combination studies. From this perspective, the pre- and post-operative clinical settings in cancer patients who are not candidate to other medical treatments represent an ideal context to assess the effects of the FMD without other confounding factors. This trial primarily aims to assess the immunological and metabolic changes induced by the FMD in the pre-operative and post-operative setting in breast cancer and melanoma patients. Three cohorts of patients will be enrolled: 1) Cohort A: patients with resectable breast cancer (cT1N0M0 stage or cT1cN1M0-cT2cN0M0 stages not requiring pre-operative systemic treatment at the judgment of the investigator) who are candidate to curative surgery; 2) Cohort B: patients with malignant melanoma patients candidate to dissection of the lymph node basin because of a positive sentinel lymph node (stage IIIA-IIIB-IIIC); 3) Cohort C: patients with resected malignant melanoma (including radicalization and, in case, lymph node dissection) who are not candidate to any adjuvant treatment, but only to clinical and radiological follow-up (stage IIB-IIC). Patients in cohorts A and B will undergo one 5 days FMD cycle about 13-15 days before surgical removal of primary tumor (breast) or lymph nodes (breast, melanoma). Patients in cohort C will undergo 4 consecutive FMD cycles every 28 days, starting one month after surgery.

Trial registration: ClinicalTrials.gov – NCT03454282

3. Title: Os-10-3 -- A Randomized, Phase II Clinical Trial of a Controlled Diet Prior to Selected Chemotherapy Treatment in Breast and Prostate Cancer to Evaluate the Impact on Toxicity and Efficacy

Status: Ongoing
Participants: Chemolieve in breast and prostate cancer; 120 participants (60 patients for breast cancer and 60 patients for prostate cancer)
Study: Randomized, Interventional, Parallel Assignment (January 29, 2013 – January 29, 2020); Estimated Study Completion Date: January 29, 2021
Location: University of Southern California, Los Angeles, CA; in collaboration with Norris Cancer Center and LAC+USC
Researcher: Dr. David Quinn (diquinn@med.usc.edu)

Synopsis: We are studying the effects of a medically designed low-calorie diet for women with breast cancer and men with prostate cancer receiving chemotherapy. We believe the diet will help prevent or lessen chemotherapy side effects such as nausea and fatigue and may also help chemotherapy be more effective against the cancer. We want to obtain preliminary estimates of the impact of a restricted diet on toxicity and efficacy of chemotherapy for breast and prostate cancer

This randomized phase II trial studies how well a controlled low-calorie diet works in reducing side effects and increasing response to chemotherapy in patients with breast or prostate cancer. Drugs used in chemotherapy work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Eating a special diet with low calories may reduce the side effects of chemotherapy and improve the response to treatment.

Trial registration: ClinicalTrials.gov – NCT01802346

4. Title: Phase ll Study of a Diet that Simulates Fasting in Patients Undergoing Cancer Treatment

Status: Ongoing
Participants: ProLon and solid/hematologic malignancies; 60 patients
Study: Phase II Clinical Study (Start Date: November 2017)
Location: University of Genova, Genova, Italy
Researcher: Prof. Alessio Nencioni, MD, PhD (alessio.nencioni@unige.it); Francesca Valdemarin (francescavaldemarin@me.com)

Synopsis: Every year in Europe, around 3.5 million new cases of cancer are diagnosed and 1.8 million patients die of cancer. This scenario generates the need to evaluate new therapeutic approaches, including metabolic approaches and approaches that exploit new, emerging properties of the neoplastic cells themselves. Numerous studies show how fasting cycles exert powerful antitumor effects in experimental animals, where these effects are reported by laboratories independent both in models of solid tumors (such as breast cancer, and lung cancer) of the colorectal, melanomas and gliomas that of hematological tumors (especially of leukemia acute lymphatic system). Moreover, in animal models, fasting cycles have been shown to increase both the tolerability and the efficacy of chemotherapeutic agents, including cyclophosphamide, etoposide, doxorubicin, oxaliplatin and cisplatin. Specifically, in the case of doxorubicin, fasting has been shown to exert protective effects also in case of cardiac toxicity, while in the case of cisplatin, fasting has been shown to reduce neurological side effects. At least in part, the antineoplastic action and the strengthening of chemotherapy by fasting appears to be due to the promotion of antitumor immunity and sensitization of neoplastic cells to the action of the immune system. These observations led to the development of fasting-mimicking diets (FMD) which, on the basis of surveys, are better accepted than fasting by patients and that recreate the antineoplastic and protective effects and protect from the side effects of fasting itself.

5. Title: BRCA Main Home Study -- Use of FMD in a Group of People Who Carry Mutations in Susceptibility Genes for Breast Cancer

Status: Ongoing
Participants: ProLon and risk of breast cancer (300 patients)
Study: Randomized Pilot Study (June 1, 2018 - May 31, 2019); Estimated Study Completion Date: May 31, 2020
Location: University Hospital, Policlinico Paolo Giaccone di Palermo, Palermo, Italy
Researcher: Prof. Giovanni Mirisola (mario.mirisola@unipa.it)

Synopsis: Women carrying harmful mutation in BRCA1 or BRCA2 gene are at higher risk to develop breast and/or ovarian cancer than the general population. Many observations lead to the hypothesis that breast cancer risk may be increased in women with elevated plasma insulin-like growth factor 1 (IGF-1) and insulin levels. Targeting the IGF system is therefore a promising anticancer therapy and a new tool for oncologists. Evidence from bio-gerontology research from our laboratories show that cycles of short-term fasting/starvation (STS) or low calorie diet can improve health span of laboratory animals, whose effect is partly mediated by reduced circulating IGF-1. Investigators in our group have demonstrated that protein consumption, especially animal proteins, increases IGF-1 level and is associated with elevated cancer risk in a US cohort ranging from age 50 to 65 (PMID: 26094889). It was also showed that alternating prolonged fasting and nutrient-rich medium extended yeast lifespan independently of the status of the established pro-longevity genes. Prolonged Fasting (PF) has also been shown in preliminary studies to decrease the side effects of chemotherapy, an effect now being tested in multiple larger randomized clinical trials (PMID: 26590477). The main hypothesis of this proposal is that a combination of protein restriction, fasting, fasting mimicking diet (FMD), and restriction of specific amino acids may be able to decrease cancer incidence in a cohort of people at high risk of developing tumors (BRCA1/2). Our group plan to verify the safety, effectiveness and impact of a specially formulated longevity dietary regimen (low protein fish- and plant-based) and of FMD repeated cycles on the levels of endogenous hormones in a cohort of people at increased cancer risk. Since the duration of the project will not give us the opportunity to directly measure cancer incidence in humans we will test: 1a) the variation of a number of widely recognized susceptibility biomarkers predictive of cancer incidence in a cohort human carriers of BRCA1/2 mutations in response to the dietary interventions; 1b) cancer incidence and progression in genetically engineered mice (K14Cre Brca1flox/flox Trp53+/flox and K14Cre Brca1+/flox Trp53-/- mice) predisposed to develop hereditary breast cancer in response to corresponding dietary interventions. Investigators will also test epigenetic alterations associated with these interventions in: 2a) DNA samples from muscle biopsies of a subgroup of humans; 2b) breast epithelial tissue in mice.

Trial registration: ClinicalTrials.gov – NCT03570125

6. Title: DIetary REstriction as an Adjunct to Neoadjuvant ChemoTherapy for HER2 Negative Breast Cancer (DIRECT)

Status: Completed
Participants: FMD and Breast Cancer; 131 participants
Study: Randomized, Interventional, Parallel Assignment (February 2014 – November 2018)
Location: Leiden University Medical Center, Leiden, Netherlands
Researcher: Judith R Kroep, MD, PhD +31715263464 (j.r.kroep@lumc.nl); Stefanie de Groot, MD +31715263464 (s.de_groot2@lumc.nl)

Synopsis: Preclinical studies provide strong support for the concept that fasting evokes resistance to multiple forms of stress. Fasting reduces plasma levels of growth factors and modulates intracellular nutrient sensing systems, thereby diverting energy from growth to maintenance. Accordingly, the currently available preclinical evidence suggests that short-term fasting protects normal cells against the perils of chemotherapy. In contrast, cancer cells are not protected, as a result of their self-sufficiency in growth signals. This phenomenon is termed Differential Stress Resistance (DSR). DSR reduces the severity of toxic side-effects of chemotherapy and interestingly, it simultaneously renders cancer cells more vulnerable to chemotherapeutics. Importantly, extensive preclinical evidence and preliminary clinical data indicate that a specifically designed very low calorie, low amino acid substitution diet (“Fasting Mimicking Diet, FMD”) has effects on cancer therapy that are very similar to those of fasting. This study aims to evaluate the impact of the FMD on tolerance to and efficacy of neoadjuvant chemotherapy in women with stage II or III breast cancer.

Trial registration: ClinicalTrials.gov – NCT02126449

7. Title: Fasting and Nutritional Therapy in Patients with Advanced Metastatic Prostate Cancer

Status: Ongoing
Participants: Fasting and advanced metastatic prostate cancer; 60 participants
Study: Randomized, Interventional, Parallel Assignment (April 2016 – July 2019); Estimated Study Completion Date: December 2019
Location: Charite University, Berlin, Germany
Researcher: Dr. Ursula Steiner +49 30 8445 2577 (ursula.steiner@charite.de); Dr. Kurt Miller +49 30 8445 2577 (kurt.miller@charite.de)

Synopsis: Prostate cancer is in Germany with approximately 25% of all cancers the most common cancer among man. Assumably there will be an increase in prostate cancer in the next few years because of demographic factors. The progressive metastatic prostate cancer often develops an androgen resistance. This so-called Castration-Resistant Prostate Cancer (CRPC) is not responsive to androgen deprivation therapy. Depending on symptoms and progression first-line chemotherapy – docetaxel and abiraterone are available.

Intermittent fasting as a form of caloric restriction has been studied most extensively experimentally in recent years. It showed consistent beneficial effects on relevant inflammatory and oncological pathways. In the field of preclinical oncology research groups have recently focused on intermittent fasting with chemotherapeutic treatment and promising experimental data have been published. In summary, the combination of fasting and chemotherapy was more effective in various cancer animal models than chemotherapy alone.

Trial registration: ClinicalTrials.gov – NCT02710721

8. Title: Fasting and Cancer Treatment in Humans -- A Case Series Report

Status: Completed
Participants: Fasting and chemotherapy;10 patients
Study: Case Report
Location: University of Southern California, Los Angeles, CA
Researcher: Valter Longo, PhD  

Published: Safdie, F. M., Dorff, T., Quinn, D., Fontana, L., Wei, M., Lee, C., … Longo, V. D. (2009). Fasting and cancer treatment in humans: A case series report. Aging (Albany NY), 1(12), 988–1007.

Abstract: Short‐term fasting (48 hours) was shown to be effective in protecting normal cells and mice but not cancer cells against high dose chemotherapy, termed Differential Stress Resistance (DSR), but the feasibility and effect of fasting in cancer patients undergoing chemotherapy is unknown. Here we describe 10 cases in which patients diagnosed with a variety of malignancies had voluntarily fasted prior to (48‐140 hours) and/or following (5‐56 hours) chemotherapy. None of these patients, who received an average of 4 cycles of various chemotherapy drugs in combination with fasting, reported significant side effects caused by the fasting itself other than hunger and lightheadedness. Chemotherapy associated toxicity was graded according to the Common Terminology Criteria for Adverse Events (CTCAE) of the National Cancer Institute (NCI). The six patients who underwent chemotherapy with or without fasting reported a reduction in fatigue, weakness, and gastrointestinal side effects while fasting. In those patients whose cancer progression could be assessed, fasting did not prevent the chemotherapy‐induced reduction of tumor volume or tumor markers. Although the 10 cases presented here suggest that fasting in combination with chemotherapy is feasible, safe, and has the potential to ameliorate side effects caused by chemotherapies, they are not meant to establish practice guidelines for patients undergoing chemotherapy. Only controlled‐randomized clinical trials will determine the effect of fasting on clinical outcomes including quality of life and therapeutic index.

9. Title: Effects of Short-Term Fasting on Tolerance to Adjuvant Chemotherapy in Breast Cancer Patients

Status: Completed
Participants: Fasting and Chemotherapy in HER2- negative breast cancer; 13 patients
Study: Randomized Pilot Study, Interventional, Parallel Assignment (March 2011 – April 2013); Estimated Study Completion Date: January 2015
Location: Leiden University Medical Center, Leiden, Netherlands
Researcher: Judith R Kroep, MD, PhD +31 71 5263464 (j.r.kroep@lumc.nl); Stefanie de Groot, MD +31 71 5263464 (s.de_groot2@lumc.nl)

Published: De Groot, S., Vreeswijk, M. P., Welters, M. J., Gravesteijn, G., Boei, J. J., Jochems, A., … Kroep, J. R. (2015). The effects of short-term fasting on tolerance to (neo) adjuvant chemotherapy in HER2-negative breast cancer patients: a randomized pilot study. BMC Cancer, 15, 652.

Synopsis: Preclinical evidence shows that short-term fasting (STF) protects healthy cells against side effects of chemotherapy and makes cancer cells more vulnerable to it. This pilot study examines the feasibility of STF and its effects on tolerance of chemotherapy in a homogeneous patient group with early breast cancer (BC).

Methods: Eligible patients had HER2-negative, stage II/III BC. Women receiving (neo)-adjuvant TAC (docetaxel/doxorubicin/cyclophosphamide) were randomized to fast 24 h before and after commencing chemotherapy, or to eat according to the guidelines for healthy nutrition. Toxicity in the two groups was compared. Chemotherapy-induced DNA damage in peripheral blood mononuclear cells (PBMCs) was quantified by the level of γ-H2AX analyzed by flow cytometry.

Results: Thirteen patients were included of whom seven were randomized to the STF arm. STF was well tolerated. Mean erythrocyte- and thrombocyte counts 7 days post-chemotherapy were significantly higher (P = 0.007, 95 % CI 0.106-0.638 and P = 0.00007, 95 % CI 38.7-104, respectively) in the STF group compared to the non-STF group. Non-hematological toxicity did not differ between the groups. Levels of γ-H2AX were significantly increased 30 min post-chemotherapy in CD45 + CD3- cells in non-STF, but not in STF patients.

Conclusions: STF during chemotherapy was well tolerated and reduced hematological toxicity of TAC in HER2-negative BC patients. Moreover, STF may reduce a transient increase in, and/or induce a faster recovery of DNA damage in PBMCs after chemotherapy. Larger studies, investigating a longer fasting period, are required to generate more insight into the possible benefits of STF during chemotherapy.
Trial registration: ClinicalTrials.gov -- NCT01304251

10. Title: Short-Term Fasting Prior To Platinum-Based Chemotherapy -- Feasibility and Impact on Toxicity

Status: Ongoing
Participants: Fasting before chemotherapy; 20 patients
Study: Randomized, Interventional, Parallel Assignment (July 9, 2009 – July 9, 2021)
Location: University of Southern California, Los Angeles, CA; in collaboration with Norris Cancer Center
Researcher: Valter Longo, PhD; Dr. David Quinn (diquinn@med.usc.edu) 

Published: Dorff, T. B., Groshen, S., Garcia, A., Shah, M., Tsao-Wei, D., Pham, H., … Quinn, D. I. (2016). Safety and feasibility of fasting in combination with platinum-based chemotherapy. BMC Cancer, 16, 360. 

Synopsis: Short-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum-based chemotherapy to determine safety and feasibility in cancer patients.

Methods: 3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as ≥ 3/6 subjects in each cohort consuming ≤ 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay. Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state.

Results: The median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for ≥48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period.

Conclusion: Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An ongoing randomized trial is studying the effect of 72 h of fasting.

Trial registration: ClinicalTrials.gov -- NCT00936364

11. Title: Short-Term Fasting During Chemotherapy in Patients with Gynecological Cancer -- A Randomized Controlled Cross-over Trial (FIT)

Status: Completed
Participants: FMD and gynecological cancer; 50 participants
Study: Randomized, Interventional, Crossover Assignment (October 2013 – March 2015)
Location: Charite University, Berlin, Germany
Researcher: Andreas Michalsen, MD, PhD +49 30 8050 5691 (andreas.michalsen@immanuelalbertinen.de)

Published: Bauersfeld SP, Kessler CS, Wischnewsky M, Jaensch A, Steckhan N, Stange R, Kunz B, Brückner B, Sehouli J, Michalsen A. The effects of short-term fasting on quality of life and tolerance to chemotherapy in patients with breast and ovarian cancer: a randomized cross-over pilot study. BMC Cancer. 2018 Apr 27;18(1):476. doi: 10.1186/s12885-018-4353-2.

Synopsis: This pilot trial aimed to study the feasibility and effects on quality of life (QOL) and well-being of short-term fasting (STF) during chemotherapy in patients with gynecological cancer.

Methods: In an individually randomized cross-over trial patients with gynecological cancer, 4 to 6 planned chemotherapy cycles were included. Thirty-four patients were randomized to STF in the first half of chemotherapies followed by normocaloric diet (group A; n = 18) or vice versa (group B; n = 16). Fasting started 36 h before and ended 24 h after chemotherapy (60 h-fasting period). QOL was assessed by the FACIT-measurement system.

Results: The chemotherapy-induced reduction of QOL was less than the Minimally Important Difference (MID; FACT-G = 5) with STF but greater than the MID for non-fasted periods. The mean chemotherapy-induced deterioration of total FACIT-F was 10.4 ± 5.3 for fasted and 27.0 ± 6.3 for non-fasted cycles in group A and 14.1 ± 5.6 for non-fasted and 11.0 ± 5.6 for fasted cycles in group B. There were no serious adverse effects.

Conclusion: STF during chemotherapy is well tolerated and appears to improve QOL and fatigue during chemotherapy. Larger studies should prove the effect of STF as an adjunct to chemotherapy.

Trial registration: ClinicalTrials.gov – NCT01954836

12. Title: Fasting Mimicking Diet in Patients Receiving Chemo-Immunotherapy for Treatment of Metastatic Non-Small Cell Lung Cancer

Status: Ongoing
Participants: FMD and lung cancer; 40 patients
Study: Randomized Clinical Trial (Start Date: April 15, 2019)
Location: Indiana University Melvin and Bren Simon Cancer Center, Indianapolis, IN
Researcher: Shadia Jalal, MD (sjalal@iu.edu)

Synopsis: To determine the effect of Fasting-mimicking diet (FMD) on circulating tumor cells (CTCs) in patients with advanced NSCLC receiving chemo-immunotherapy.

To compare an absolute reduction and/or a percentage reduction in CTCs in patients receiving FMD compared to regular diet (RD)

To assess DNA damage via measurement of γ-Η2ΑΧfoci in CTCs compared to PBMCs of patients receiving FMD or RD

To demonstrate an increase in platinum lesions measured by ICP Mass spectrometry in tumor tissue (when available) and PBMCs of patients receiving FMD compared to RD

To demonstrate increase in Tumor-infiltrating lymphocytes in patients undergoing FMD compared to RD by obtaining optional tumor tissue samples when available.

13. Title: Effects of Fasting Mimicking Diet on Central and Peripheral Components of Fatigue, Muscular Resistance

Status: Ongoing
Participants: Prolon and muscular fatigue and strength; 72 participants
Study: Randomized Clinical Trial
Location: University of Verona, Verona, Italy
Researcher: Prof. Matteo Bertucco (matteo.bertucco@univr.it)

Synopsis: The aim of the study is to test a Fasting Mimicking Diet for its efficacy on improving muscular resistance and endurance. Intermittent or Periodic Fasting have been reported to promote lifespan extension and provide a range of protective effects, including hematopoietic stem cell generation and protection against chemotherapy-induced immunosuppression. However, it is still unknown whether stem cell generation due to intermittent or Periodic Fasting has effects on muscular resistance and endurance. We will perform a randomized clinical trial to test the efficacy of the FMD on improving muscular strength, muscular resistance and endurance in physically active young adults (18-40 years of age). The study will include two arms: Control (Placebo diet) and FMD (3 cycles of 5 days fasting-mimicking diet within two months). Study endpoints will include muscular strength evaluation of lower limbs, cardio-pulmonary responses, neuromuscular function and muscle architecture.

14. Title: Primitive Glomerulonephritis and Chronic Kidney Disease in Conservative Therapy with eGFR ≤ 60 ml/min (3 stage kdoqi)

Status: Ongoing
Participants: ProLon and glomerulonephritis and chronic kidney disease; 32 patients
Study: Prospective Clinical Trial, Crossover Assignment
Location: Sapienza University, Rome, Italy
Researcher: Prof. Alessandro Laviano, MD, PhD (alessandro.laviano@uniroma1.it)

Synopsis:

Primary endpoints:

1.Evaluate the reduction of IGF-1 after three cycles of FMD in patients affected by primary glomerulonephritis with MRC (3 stage KDOQI).

Secondary endpoints:

2.To evaluate the systemic effects of the use of FMD through some markers of inflammation, oxidative stress and endothelial dysfunction, major cardiovascular risk factors, in patients with MRC (3 stage KDOQI).

3.Evaluate the systemic effects of the use of FMD on the cognitive component.

4.Evaluate the systemic effects of the use of FMD on regenerative capacity, leading to a possible increase in renal stem cells CD133 +, CD24 +, CD45 +, CD34 + and CD309 + in blood and urine.

15. Title: Randomized Pilot Study to Evaluate the Efficacy and Safety of ProLon, a Fasting Mimicking Diet, as Add-On Therapy in Hashimoto’s Thyroiditis

Status: Ongoing
Participants: ProLon Diet and Hashimoto’s Thyroiditis; 60 patients and 60 controls
Study: Randomized Pilot Study
Location: Regenerative Medicine Center, Pittsburg, Pennsylvania
Researcher: Valerie Donaldson, MD (valdonaldson@gmail.com); Allianna Schneider, Health Coach (rmc.allianna@gmail.com)

Synopsis: We will conduct a randomized pilot study to investigate the effect of the ProLon diet on autoimmune and inflammatory status in Hashimoto’s thyroiditis treatment in an adult population (18-70 years old) receiving standard thyroid medication, compared to the control arm following a normal diet”. Dose of thyroid medication must not be changed for 3 months while ProLon kits are consumed, and the patient needs to be stable on the same medication dose for 3 months prior to the study.

The proposed research will examine the change on Hashimoto’ s related symptoms trough the evaluation of the ThyPRO questionnaire and the thyroid antibodies titer after completing three cycles of the ProLon® diet, a low-calorie, fasting-mimicking diet.

The ProLon® diet is a 5 days vegetarian dietary program in which participants consume only the prepackaged foods (800-1150 calories/day) allotted for each day. Study will generate quantitative data for TPO and thyroglobulin antibodies drawn during the ProLon® diet and at 4 weeks, 8 weeks, and 12 weeks after finishing the third cycle of ProLon®.

Research will also track the how body composition changes. Body Composition Analysis will provide quantitative data for total body weight, lean body mass, body fat mass, BMI, percent body fat, intracellular water, extracellular water, total body water, basal metabolic rate, and segmental lean analysis. Inflammation panel and assessment of CVD risk will also be evaluated as secondary endpoints

16. Title: Randomized Phase I / II Study of a Hypoproteic Diet in Patients with Cognitive Impairment

Status: Planned
Participants: ProLon + Supplement AD (Alzheimer’s Disease) and AD or MCI (Mild Cognitive Impairment); 60 patients affected by mild AD (MMSE 18-23) and 60 patients affected by MCI
Study: Phase I/II Randomized Clinical Trial
Location: University of Genova, Genova, Italy
Researcher: Prof. Patrizio Odetti, MD, PhD (odetti@unige.it)

Synopsis: In experimental animal models, caloric restriction diets have shown protective effects on the aging process, on oxidative stress and on the process of neurodegeneration, factors implicated in the pathogenesis of Alzheimer’s disease. Diet cycles with low levels of sugars and proteins followed by diets with normal levels of these lead to temporary reductions in growth hormone levels and IGF-1. Both are potential mediators of the neuroprotective and regenerative effects of these diets not only in mice, but also in monkeys and men. However, strongly calorie restricted diets are often difficult to maintain over time and are frequently associated with even significant side effects and with progressive weight loss, particularly of lean mass. In a mouse model of AD, it has been shown that periodic cycles of a “fasting-mimicking” diet (FMD) restricted in protein content (protein-restricted – PR-FMD) but not in terms of calories are able to reduce levels circulating plasma IGF-1 with significant effects of contrast to the process of neurodegeneration. In particular, such FMD has been shown to reduce by about 30-70%, the levels of hyperphosphorylated tau protein (one of the typical markers of AD) at the hippocampal level, reducing the correlated age deficit of cognitive performance. More recently, a significant neuroregenerative effect (associated with a clinical improvement of motor coordination and memory) has been demonstrated in mice subjected to a diet based on a similar FMD during their “average life” (months 16-30).

Recent clinical studies have shown that FMDs are generally safe and well tolerated in healthy subjects and in people with multiple sclerosis, even with multiple monthly cycles and in individuals over 65. Furthermore, it is important to underline that, in healthy subjects, cycles of FMD have reduced various risk factors for aging diseases (including AD), including arterial hypertension, pre-diabetes, accumulation of visceral adipose tissue and high circulating levels of IGF-1 and C-reactive protein. Recently, in a study conducted at the University of Southern California (USC), 3 cycles of a week-long PR-FMD have led to a significant improvement in cognitive performance in healthy volunteers.

17. Title: Multiple Sclerosis

Status: Planned
Participants: ProLon and Multiple Sclerosis; 20 patients
Study: Randomized Clinical Trial
Location: Clinica Neurologica Università di Genova, Genova, Italy
Researcher: Prof. Gianluigi Mancardi (glmancardi@neurologia.unige.it)

Synopsis:  

Primary Objective:

To evaluate the safety and tolerability of 3 cycles of a 7 days FMD in patients affected by RRMS, already treated with interferon-beta-1° (22 or 44 mgx3).

18. Title: Studio Randomizzato di Fase I/II di una Dieta Ipoproteica in Pazienti con Sindrome Metabolica

Status: Planned
Participants: Metabolic Syndrome; 120 patients
Study: Randomized Clinical Trial
Location: Genova, Italy
Researcher: 

Synopsis:

19. Title: Safety and Feasibility of Fasting in Combination with Platinum-Based Chemotherapy

Status: Completed
Participants: Fasting before chemotherapy; 20 patients
Study: Randomized, Interventional, Parallel Assignment
Location: University of Southern California, Los Angeles, CA; in collaboration with Norris Cancer Center
Researcher: Valter Longo, PhD; Dr. David Quinn (diquinn@med.usc.edu)

Published: Dorff, T. B., Groshen, S., Garcia, A., Shah, M., Tsao-Wei, D., Pham, H., … Quinn, D. I. (2016). Safety and feasibility of fasting in combination with platinum-based chemotherapy. BMC Cancer, 16, 360.

Synopsis: Short-term starvation prior to chemotherapy administration protects mice against toxicity. We undertook dose-escalation of fasting prior to platinum-based chemotherapy to determine safety and feasibility in cancer patients.

Methods: 3 cohorts fasted before chemotherapy for 24, 48 and 72 h (divided as 48 pre-chemo and 24 post-chemo) and recorded all calories consumed. Feasibility was defined as ≥ 3/6 subjects in each cohort consuming ≤ 200 kcal per 24 h during the fast period without excess toxicity. Oxidative stress was evaluated in leukocytes using the COMET assay. Insulin, glucose, ketones, insulin-like growth factor-1 (IGF-1) and IGF binding proteins (IGFBPs) were measured as biomarkers of the fasting state.

Results: The median age of our 20 subjects was 61, and 85 % were women. Feasibility criteria were met. Fasting-related toxicities were limited to ≤ grade 2, most commonly fatigue, headache, and dizziness. The COMET assay indicated reduced DNA damage in leukocytes from subjects who fasted for ≥48 h (p = 0.08). There was a non-significant trend toward less grade 3 or 4 neutropenia in the 48 and 72 h cohorts compared to 24 h cohort (p = 0.17). IGF-1 levels decreased by 30, 33 and 8 % in the 24, 48 and 72 h fasting cohorts respectively after the first fasting period.

Conclusion: Fasting for 72 h around chemotherapy administration is safe and feasible for cancer patients. Biomarkers such as IGF-1 may facilitate assessment of differences in chemotherapy toxicity in subgroups achieving the physiologic fasting state. An ongoing randomized trial is studying the effect of 72 h of fasting.

Trial registration: ClinicalTrials.gov -- NCT00936364, registered prospectively on July 9, 2009.

20. Title: To Evaluate the Efficacy and Safety of ProLon, a Fasting Mimicking Diet on Metabolic Syndrome

Status: Planned
Participants: ProLon and metabolic syndrome; 400 patients
Study: Phase II, Randomized, Placebo-Controlled Study
Location: University of Southern California, Los Angeles, CA; USC Norris Keck Hospital in collaboration with UCLA School of Medicine
Researcher: Kurt Hong, MD (kurthong@usc.edu)

Synopsis: This study is meant to evaluate whether ProLon, a dietary intervention mimicking fasting for five days per month, is better than a low-calorie placebo in decreasing metabolic risk factor score in patients diagnosed with metabolic syndrome. Patients will undergo through six cycles of diet (ProLon or Placebo) and six months follow up, and will be assessed for metabolic risk factor, metabolic profile, life quality and general health throughout the study.

21. Title: Evaluate the Efficacy and Safety of a Fasting Mimicking Diet, as Add-on Therapy, on Clinical Response in Patients with Active, Mild to Moderate Ulcerative Colitis

Status: Planned
Participants: FMD and Ulcerative Colitis; 200 patients
Study: Prospective, Randomized, Placebo-Controlled Trial
Location: University of Southern California, Los Angeles, CA; in collaboration with USC Norris Keck Hospital
Researcher: Dr. Caroline Hwang, Dr. Kurt Hong (kurthong@usc.edu)

Synopsis: Evaluate the Efficacy and Safety of a Fasting-Mimicking Diet, as Add-on Therapy, on Clinical Response in Patients with Active, Mild-to-Moderate, Ulcerative Colitis

To test the efficacy of the Fasting Mimicking diet in improving ulcerative colitis treatment in an adult population (18-65 years of age) receiving their standard UC therapy.

22. Title: Evaluate the Efficacy and Safety of a Fasting Mimicking Diet, as Add-On Therapy, on Clinical Response in Patients with Active Crohn’s Disease

Status: Planned
Participants: FMD and Crohn’s Diseases; 200 Patients
Study: Prospective, Randomized, Placebo-Controlled Trial
Location: University of Southern California, Los Angeles, CA; in collaboration with USC Norris Keck Hospital
Researcher: Dr. Caroline Hwang, Dr. Kurt Hong (kurthong@usc.edu)

Synopsis: Evaluate the Efficacy and Safety of a Fasting-mimicking Diet, as Add-on Therapy, on Clinical Response in Patients with Ac Crohn’s disease.

To test the efficacy of the Fasting Mimicking diet in improving ulcerative colitis treatment in an adult population (18-65 years of age) receiving their standard IBD therapy.

23. Title: Five Meals a Day vs. Two Meals a Day -- To Evaluate the Consumption of Two Meals Plus One Snack per Day Compared to Five Meals per Day on Initial Weight Loss and Weight Maintenance over the Period of 12 Months in Overweight and Obese Individuals (with BMI >27)

Status: Planned
Participants: Healthy individuals who are overweight or obese
Study: Prospective, Randomized, Placebo-Controlled Trial
Location: University of Southern California, Los Angeles, CA; in collaboration with USC Norris Keck Hospital
Researcher: Valter Longo; PhD; Dr. Caroline Hwang; Dr. Kurt Hong (kurthong@usc.edu)

Synopsis: The aim of our study is to compare the effect of five meals vs two meals a day (breakfast and lunch or breakfast and dinner with one snack with 270 kcal, as this regimen allows a reasonable fasting time, yet is sustainable in the long term) on body weight, waist circumference, BMI in individuals with BMI >27. It is hypothesized that eating only two meals per day with one snack would reduce body weight and might be advantageous from a metabolic perspective than five meals a day.

24. Title: Fasting Mimicking Diet Study Protocol

Status: Ongoing
Participants: FMD and CVD and CHD risk factors; 80 subjects (40 subjects in the control group and 40 subjects in the treatment group); 35-75 years old
Study: Randomized Clinical Trial (January 2019 – November2019)
Location: Hypertension Institute (HI) of Nashville, Nashville, TN and University of Southern California (USC), Los Angeles, CA  
Researcher: Mark C. Houston, MD, MS, MSc (boohouston@comcast.net); Sissy Denton, RN, BSN (sissy.denton@comcast.net)

SYNOPSIS: Determine the effects of the Fasting Mimicking Diet (FMD) on cardiovascular biomarkers, Coronary Heart Disease (CHD) risk factors (body weight, BMI, body composition, blood pressure, serum lipid levels and dysglycemia blood measurements), non-invasive cardiovascular testing for endothelial function, arterial stiffness of large and small arteries, and autonomic function testing in adult subjects over a five-month study period.

The ProLon arm participants are consuming the diet once a month for 4 months, then returning after three months for follow-up. The Mediterranean arm participants are following guidelines given regarding mediterranean eating, same time frame as above

25. Title: PCI.GC.002 -- A Prospective Pilot Cohort Study of Patients with a Known Diagnosis of Cancer, to Document its Metabolic Effects, including Cancer Fatigue, and Metabolic Syndrome, as well as Lifestyle Changes in the Clinic

Status: Ongoing
Participants: Chemolieve in prostate cancer patients at risk of metabolic syndrome (10-15 patients, 18-80 years old)
Study: Prospective Clinical Study
Location: Prostate Cancer Institute, Galway Clinic and National University of Galway (NUIG), Ireland
Researcher: Prof. Frank Sullivan, MBBS, MSc (frank.sullivan@galwayclinic.com); Valter Longo, PhD

SYNOPSIS: We aim to validate an approach to measuring, tracking and addressing Oxidative Stress and Inflammation status as key indicators of physiological adaptation, fatigue and disease states in cancer patients, and ultimately improve recovery in patients with Cancer Related Fatigue (CRF) in maladapted and fatigued states. We further wish to monitor the role of supportive recommendations (e.g. hydration, diet, rest, exercise, stress reduction) often recommended for these symptoms. This will be done by describing and quantitating baseline patient efforts as best as possible, in this broad cohort. Where possible evidence-based suggestions and advice will be given to patients, to help them with their diet, exercise and stress management. It is recognized that this study will NOT lead us to recommendations as to the value of any intervention observed, it will merely serve as a baseline, from which potential further studies might lead to recommendations in the future.

26. Title: Fasting Mimicking Diet, Modified Ketogenic Diet, and Time Restricted Feeding as Adjuvant Therapy for Newly Diagnosed Glioblastoma Multiforme Patients

Status: Planned
Participants: 20 patients with GBM enrolled after tumor resection and prior to chemoradiotherapy. Enrolled subjects will be placed on 12 weeks trial of the dietary intervention while receiving standard of care cancer treatment (Radiation + Temozolomide)
Study: Prospective, Single-Arm Pilot Study
Location: Virginia Tech Carillon School of Medicine, Roanoke, Virginia  
Researcher: Dr. Lisa Apfel; Steven Svoboda (sasvoboda@carilionclinic.org)

Synopsis: There is an increasing interest in the use of the ketogenic diet as an adjuvant therapy for glioblastoma multiforme (GBM) patients due to the substantial amount of preclinical and clinical literature demonstrating anti-neoplastic efficacy and safety. The ketogenic diet is postulated to work by simulating the metabolic response to fasting by promoting the utilization of ketones as a primary energy source, and depriving the glycolytic pathways utilized by malignant glioma cells for growth. Current ongoing clinical trials are investigating the most promising ketogenic regimen for glioblastoma patients, as well as, compatibility with other anti-cancer treatments, feasibility, safety, and impact on quality of life.

Objectives: The primary aim of this pilot intervention study is to obtain preliminary evidence of the feasibility and tolerability of a novel ketogenic diet protocol in newly diagnosed GBM patients. Secondary aims include evaluating safety, efficacy, and patient impact of the diet. The monthly protocol consists of a patented 5 days fasting mimicking diet program (L-Nutra, CA, USA) followed by a modified ketogenic diet and time restricted feeding.

Methods: A prospective, single-arm pilot study will be undertaken in 20 subjects with GBM. Patients will be enrolled after tumor resection and prior to chemoradiotherapy. Enrolled subjects will be placed on a 12-week trial of the dietary intervention while receiving standard of care cancer treatment (Radiation + Temozolomide). A study dietitian will provide guidance and teaching of the diet protocol, as well as, monitoring and diet adjustment to ensure adherence. Feasibility will be assessed by enrollment and retention rates, dietary adherence and tolerability questionnaires, and weekly blood ketone checks. Patient impact will be assessed by quality of life and cognitive function questionnaires, anthropometric and biochemical changes, and reported adverse effects.

Expected Outcomes: The results of this pilot study will be used to inform the feasibility and methodological design of future clinical trials investigating the effectiveness of this nutritional protocol as an adjuvant metabolic therapy in the management of patients with GBM.

27. Title: The Effect of Dietary Interventions on Endothelial Glycocalyx Dimensions and Barrier Function in South Asian Patients with Diabetic Nephropathy (Glycotreat Study)

Status: Ongoing
Participants: 90 South Asian type 2 diabetic patients with micro-albuminuria receiving a food supplement, placebo capsule or the 5 days fasting mimicking diet Prolon
Study: Double-Blind, Randomized, Controlled, Interventional, Parallel Assignment (May 3, 2018 - December 31, 2019)
Location: Leiden University Medical Centre, Leiden, Netherlands
Researcher: Anouk I. M. van der Velden, MD (a.i.m.van_der_velden@lumc.nl); Daphne H.T. ljpelaar, MD, PhD (D.H.T.ljpelaar@lumc.nl); Ton J. Rabelink, MD, PhD (A.J.Rabelink@lumc.nl)

Synopsis: Micro- and macrovascular complications are the pathological hallmarks of diabetes mellitus, with diabetic nephropathy as one of the most serious microvascular complications. South Asians have a high incidence of type 2 diabetes and a higher change to progress to end-stage renal disease than West European patients, which may be due to a higher sustained systemic and glomerular inflammation.

The endothelial glycocalyx, covering endothelial cells, is essential for maintaining vascular homeostasis. In the diabetic environment, impairment of the glycocalyx can be induced by invading macrophages which excrete the glycocalyx degrading enzyme heparanase and its activator cathepsin L. In the glomerulus, impairment of the glycocalyx results in increased permeability for albumin alongside renal and vascular inflammation. SDF-imaging is a non-invasive technique to visualize the sublingual endothelial glycocalyx and obtains parameters that reflect the microvascular health, combined in the Microvascular Health Index (MHI). In the present study, we investigate if dietary interventions, a food supplement which provides the nutritional building blocks to support and maintain the endothelial glycocalyx or a 5 days fasting mimicking diet to reduce the overall inflammatory burden, can aid in restoration of the endothelial glycocalyx and in turn improve the microvascular health within 3 months.

Trial registration: ClinicalTrials.gov -- NCT03889236

28, Title: Chronic Fasting and the Late Complications of Diabetes: A Prospective Exploratory Randomized Controlled Study in Patients with Diabetes Mellitus Type 2

Status: Ongoing
Participants: Patients with diabetes mellitus type 2 and diabetic nephropathy; 60 participants
Study: Randomized, Controlled Clinical Trial
Location: Department of Endocrinology and Clinical Chemistry (Internal Medicine I), University Hospital Heidelberg, Heidelberg, Germany
Researcher: Alba Sulaj, MD (Alba.Sulaj@med.uni-heidelberg.de)

Synopsis: Fasting has been shown to cause beneficial effects on lifespan, stress-resistance and against oxidative damage. To minimize the burden of fasting, a “fasting-mimicking-diet” (FMD) was developed. FMD mimics metabolically fasting effects in the organism through a low calorie, low protein, low carbohydrate and high in unsaturated fats dietary composition. The aim of this study is to investigate the late complications of diabetes during periodic FMD intake in patients with diabetes mellitus type 2 and diabetic nephropathy. This is a prospective randomized controlled monocentric intervention study. Patients with diabetes mellitus type 2 and elevated albuminuria are randomized in two groups: an intervention group where patients receive periodically for 5 consecutive days once a month FMD, and a control group where patients receive Mediterranean diet. Study duration is 6 months. Both groups undergo regular examinations regarding the late complications of diabetes. Change of albuminuria is analyzed as primary endpoint.

Trial Registration: German Register for Clinical Studies (DRKS) -- DRKS00014287

29. Title: Pilot Study on the Effects of Fasting Mimicking Diet (FMD) in Women with Polycystic Ovary Syndrome (PCOS)

Status: Planned
Participants: 30 women (15 FMD and 15 control); FMD ProLon 1/month for 6 months
Study: Phase I Randomized, Controlled, Unblinded 2 Arms
Location: University of Salento, Lecce, Italy and Integrative Medical Group of Irvine, CA
Researcher: Anna Guidetti (anna.guidetti@unisalento.it); Dr. Felice Gersh (fgersh@integrativemgi.com)

Synopsis: The purpose of the study is to evaluate the effects of the Fasting Mimicking Diet (FMD) in women with Polycystic Ovary Syndrome (PCOS). The primary objective is to restore the regularity of the menstrual cycle.

30. Title: Fasting Mimicking Diet -- A Randomized Trial on Feasibility, Safety and Effects of Multicycle Dietary Intervention on Side Effects of Aromatase Inhibitors Treatment in Post-Menopausal Patients with Breast Cancer

Status: Planned
Participants: 60 women treated with adjuvant AI + 5 days Chemolieve for 12 weeks (1cycle/month to 3 cycles)
Study: Prospective, Randomized Clinical Trial
Location: Instituto Europeo di Oncologia, Milano, Italy
Researcher: Ida Minchella, MD (ida.minchella@ieo.it); Giuseppe Curigliano, MD, PhD (giuseppe.curigliano@ieo.it); Valter Longo, PhD

Synopsis: In postmenopausal women with hormone receptor-positive early-stage breast cancer, the use of aromatase inhibitors (AIs) is associated with improved clinical outcomes compared with tamoxifen therapy. Adjuvant endocrine therapy is not associated with the more severe, acute toxicities of chemotherapy, and can therefore be taken for many years. At present, the standard duration of postoperative adjuvant endocrine therapy is 5-10 years. Women receiving such endocrine therapy may experience treatment-related side effects that negatively affect health-related quality of life (QoL) and adherence to therapy. Prevention and treatment of adverse events associated with long-term endocrine therapy is particularly important in the adjuvant setting, where patients are clinically cancer free. There have been lots of controversies on the effect of AIs to lipid profile or CVD (cardiovascular disease) risk. The proposed prospective randomized clinical trial will test the hypothesis that FMD as an adjuvant intervention will reduce total cholesterol levels by AIs adjuvant treatment in post-menopausal women with early breast cancer. This study will enter a total of 60 women (>18 years old) with a histologic diagnosis of endocrine responsive early breast cancer. Following primary surgical therapy, all patients will receive defined standard systemic therapy. Patient on AIs treatment (at least 1 year of treatment) will be randomized to 12 weeks of FMD or only to a control group (non-intervention group, NIG).

31. Title: Phase I, Pilot, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of ProMet, a Fasting Mimicking Diet, on Inflammatory Cardiomyopathy

Status: Planned
Participants: 20 male and female subjects between 18 and 70 years of age, diagnosed with inflammatory cardiomyopathy; Total of 40 patients (20 treated and 20 placebo)
Study: Phase I Pilot Study, Randomized, Placebo-Controlled
Location: Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Germany
Researcher: Dr. Bettina Heidecker (bettina.heidecker@charite.de)

Synopsis: This study is meant to evaluate whether ProMet, a dietary intervention mimicking fasting for five days per month, can reduce inflammatory cytokines Th1 and Th17 and increase T regulatory cells and naïve T cells compared to placebo group in patients with inflammatory cardiomyopathy. Patients will undergo 6 cycles of diet (ProMet or regular diet) and a 1 year follow up, and will be assessed for the composition of the immune cells in the peripheral blood, blood cytokines, functional parameters (left ventricular ejection fraction, arrhythmias, performance during exercise stress testing), and quality of life.

Primary Objective:

To evaluate whether a periodic fasting-mimicking diet affects the composition of immune cells in the peripheral blood of patients with inflammatory cardiomyopathy based on myocardial biopsy

Secondary Objectives: To assess the effect of a periodic fasting-mimicking diet on left ventricular ejection fraction, risk for arrhythmias, performance during exercise stress testing.

Study duration: 24 months; participant duration: 18 months (6 months intervention + 12 months follow up).

32. Title: Cephalalgy

Status: Planned
Participants: 
Study:
Location: Università degli Studi di Trieste, Trieste, Italy
Researcher: Manuela Deodato (mdeodato@units.it)

Synopsis:

33. Title: Melanoma Immunotherapy and FMD

Status: Planned
Participants: 
Study: 
Location: University of Michigan, Ann Arbor, MI
Researcher: Christofer Lao, MD (clao@umich.edu)

Synopsis:

34. Title: Depression

Status: Planned
Participants: 
Study:
Location: Policlinico Paolo Giaccone, Università di Palermo, Palermo, Italy
Researcher: Antonio Russo, MD, PhD; Mario G Mirisola, PhD (mario.mirisola@unipa.it)

Synopsis:

35. Title: Liver Transplant

Status: Planned
Participants: 
Study: 
Location: University of Southern California, Los Angeles, CA; in collaboration with USC Norris Keck Hospital
Researcher: 

Synopsis: FMD for liver donors; FMD for liver recipients pre- and post-transplant.

36. Title: Obesity-Associated Olfact Deficit and FMD

Status: Planned
Participants: A group of obese and/or overweighted patients who did not pass screening criteria (BMI and/or neuropsychological testing) to undergo surgical procedure aimed at reducing weight (grastrectomy, bypass, other…); 120 patients on monthly ProLon for 6 months; Estimated duration: 48 months.
Study: Interventional Clinical Trial
Location: Department of Clinical Sciences and Translational Medicine - ENT Unit, University of Rome Tor Vergata, ITER Center for Balance and Rehabilitation Research, Rome, Italy
Researcher: Alessandro Micarelli, MD, PhD (alessandromicarelli@yahoo.it), Marco Alessandrini, Beatrice Micarelli, Giovanni Cesana

Synopsis: The increase of body weight is actually associated with a reduction in olfactory sensitivity and it has been already demonstrated that body mass and fasting states may interact in order to influence the olfactory sensitivity (Cameron JD, Goldfield GS, Doucet É. 2012. Fasting for 24 h improves nasal chemosensory performance and food palatability in a related manner. Appetite. 58(3):978–981; Palouzier-Paulignan B, Lacroix MC, Aimé P, Baly C, Caillol M, Congar P, Julliard AK, Tucker K, Fadool DA. 2012. Olfaction under metabolic influences. Chem Senses. 37(9):769–797.). In particular, differences in terms of olfactory detection and threshold found between fasting and satiety periods have demonstrated to be mainly pronounced with the increase of body weight (Pager J, Giachetti I, Holley A, Le Magnen J. 1972. A selective control of olfactory bulb electrical activity in relation to food deprivation and satiety in rats. Physiol Behav. 9(4):573–579.; Julliard AK, Chaput MA, Apelbaum A, Aim P. 2007. Changes in rat olfactory detection performance induced by orexin and leptin mimicking fasting and satiation. Behav Brain Res. 183:123–129.; Marks DR, Tucker K, Cavallin MA, Mast TG, Fadool DA. 2009. Awake intranasal insulin delivery modifies protein complexes and alters memory, anxiety, and olfactory behaviors. J Neurosci. 29(20):6734–6751.). Considering these aspects, it has been indicated that the grastric orexinergic peptide “GRELIN” behaves as an olfactory modulator between body weight and fasting state. Its receptor – indeed – is expresssed in the olfactory bulb and central infusion of GRELIN have been demonstrated to increase the detection of odorants in rodents (Tong J, Mannea E, Aimé P, Pfluger PT, Yi CX, Castaneda TR, Davis HW, Ren X, Pixley S, Benoit S, et al. 2011. Ghrelin enhances olfactory sensitivity and exploratory sniffing in rodents and humans. J Neurosci. 31(15):5841–5846.). At the same time obesity is associated with reduced hematic levels of GRELIN and it may modify the phasic suppression of this peptide after the meal (Tschöp M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML. 2001. Circulating ghrelin levels are decreased in human obesity. Diabetes. 50(4):707–709.; English P, Ghatei M, Malik I, Bloom S, Wilding J. 2002. Food fails to suppress ghrelin levels in obese humans. J Clin Endocrinol Metab. 87:2984–2987; Meyer-Gerspach AC, Wölnerhanssen B, Beglinger B, Nessenius F, Napitupulu M, Schulte FH, Steinert RE, Beglinger C. 2014. Gastric and intestinal satiation in obese and normal weight healthy people. Physiol Behav. 129:265–271.), even though this effect may vary depending on insulin sensitivity and macro-nutrient composition of the meal (Foster-Schubert KE, Overduin J, Prudom CE, Liu J, Callahan HS, Gaylinn BD, Thorner MO, Cummings DE. 2008. Acyl and total ghrelin are suppressed strongly by ingested proteins, weakly by lipids, and biphasically by carbohydrates. J Clin Endocrinol Metab. 93(5):1971–1979.). Thus it has been further demonstrated that peripheral infusion of GRELIN increase the sniffing magnitude in healthy subjects and that BMI is associated to an higher influence of the internal state on the olfactory sensitivity and that these phenomena are partly due to a postprandial reactivity of GRELIN, which has been found altered in the obesity (Stafford LD, Welbeck K. 2011. High hunger state increases olfactory sensitivity to neutral but not food odors. Chem Senses. 36(2):189–198.; English P, Ghatei M, Malik I, Bloom S, Wilding J. 2002. Food fails to suppress ghrelin levels in obese humans. J Clin Endocrinol Metab. 87:2984–2987.). Finally, as most important point, the blood infusion of this peptide in sated subjects increase the neuronal responses to food-related stimuli in cortical areas correlated to nutrition and reward, possibly contributing to the revaluation of food, mimicking a fasting state, since that such infusion also induce an exploratory sniffing in both animal and human models (Goldstone AP, Prechtl CG, Scholtz S, Miras AD, Chhina N, Durighel G, Deliran SS, Beckmann C, Ghatei MA, Ashby DR, et al. 2014. Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food. Am J Clin Nutr. 99(6):1319–1330.; Tong J, Mannea E, Aimé P, Pfluger PT, Yi CX, Castaneda TR, Davis HW, Ren X, Pixley S, Benoit S, et al. 2011. Ghrelin enhances olfactory sensitivity and exploratory sniffing in rodents and humans. J Neurosci. 31(15):5841–5846.).

Thus, given these experiences strenghtening the association between olfactory sensitivity (and more in general olfactory behaviour), which depose for an association between obesity, olfaction and craving/rewarding phenomena, the aim of the present study is to test if obese subjects – not included in surgical procedures - may benefit from a mimicking fasting protocol in order to modify their binge-eating behaviour – by means of an uncoscious olfactory re-arrangement – and thus benefit from a “spontaneous” weight reduction.

Patients will undergo one month before and one month after the implementation of FMD (lasting 6 months) - a battery of:

  • Olfactory test (sniffin’ stick test)
  • Taste Test
  • Neuropsychological tests: MMSE, TSK, HADS, DGI, usual gait speed, rapid gait speed, 400-m time, and Health ABC Physical Performance Battery (HABCPPB) score), total standing balance time, fine motor function (finger tapping time), and manual dexterity (Purdue Pegboard Test Termometro dello stress, California   Verbal Learning Test [CVLT]), visuoperceptual speed (Digit Symbol Substitution Test [DSST]), executive function (Trail Making Test part B [TMT-B]), and attention (TMT-A)
  • Blood Samples (IFOM – Milano)

37. Title: Bariatric Surgery

Status: Planned
Participants: 
Study: 
Location: BodEvolve Cosmetic Surgery & Medical Spa, Arlington, Tx
Researcher: BodEvolve Cosmetic Surgery & Medical Spa, Arlington, Tx

Synopsis: 

38. Title: Pediatric Type 1 Diabetes

Status: Planned
Participants: 
Study:
Location: IRCCS Istituto Giannina Gaslini, Genova, Italy
Researcher: Dr Giuseppe D'Annunzio; Paolo Fiore (paolofiore@gaslini.org)

Synopsis:

39. Title: Colorectal

Status: Planned
Participants: 
Study: 
Location: Leiden, Netherlands
Researcher: 

Synopsis:

40. Title: Clinical Feasibility and Efficacy of Intermittent Use of a Fasting Mimicking Diet in the Treatment of Type 2 Diabetes -- Fasting in Diabetes Treatment (FIT) Study

Status: Ongoing
Participants: ProLon and Type 2 Diabetes; 100 individuals with type 2 diabetes and a BMI ≥ 27, who are treated with diet only and have a HbA1c > 48, or who are treated with diet and a dose of metformin
Study: Randomized, Controlled, Parallel Assignment, Assessor Blinded and Prospective Interventional Study (November 5, 2018 - December 31, 2021)
Location: Leiden University Medical Centre, Leiden, Netherlands
Researcher: Prof. Hanno Pijl (h.pijl@lumc.nl); Elske van den Burg, MD (e.l.van_den_burg@lumc.nl); Marjolein Schoonakker, MD (M.P.schoonakker@lumc.nl)

  • Synopsis: Calorie restriction is the most effective way to prevent and treat type 2 diabetes mellitus (DM2). It simultaneously ameliorates all metabolic anomalies that mark the disease, including hyperglycemia, dyslipidemia and hypertension. However, chronic restriction of food intake is extremely difficult to sustain for the vast majority of patients. Intermittent fasting exerts very similar metabolic effects, but total fasting on a regular basis may be even more difficult than chronic restriction of food intake and may also present safety challenges. There is an innovative, periodic 5-day plant-based dietary program (ProLon) that mimics and may even enhance the metabolic benefits of total fasting (despite considerable calorie content). It thus alleviates the burden of fasting while retaining its upsides. We hypothesize that intermittent use of this diet for 5 days every month will significantly improve the metabolic condition of patients with type 2 diabetes and diminish prescription drug use.

    Trial registration: ClinicalTrials.gov -- NCT03811587

41. Title: FMD and Insulin Resistant Adolescents (Females)

Status: Planned
Participants: Females 12-18 years
Study: Non-randomized, Monocentric Pilot Study
Location: Centro di Dietologia e Nutrizione Pediatrica, Policlinico Umberto I, Roma, Italia
Researcher: Prof. Andrea Vania (andrea.vania@uniroma1.it); Dr. Raffaella Malandrino (raffaelmat@libero.it)

Synopsis:

42. Title: FMD AND IBD

Status: Planned
Participants: 100 patients

Patients with mild to moderate ulcerative colitis (modified (non-endoscopic) Mayo Score 2-6) or mild to moderate Crohn’s disease (CDAI score 150-450) between the ages of 18-70. Patients must have elevated stool calprotectin and/or serum inflammatory marker levels (ESR and/or CRP).

Study: Randomized Interventional Pilot Study
Location: Division of Gastroenterology & Hepatology, Stanford University School of Medicine, San Francisco, CA
Researcher: Sidhartha R. Sinha, MD (sidsinha@stanford.edu)

  • Synopsis: We anticipate enrolling up to 100 patients total in this pilot study. Subjects will be randomized to an intervention or a control group. Patients in the intervention arm follow the FMD/ProLon diet (one 5 day diet per month for up to 3 months) that is commercially available with standardized daily meals and instructions consisting of FDA generally recognized as safe ingredients. Patients in the control arm will follow their regular diet.

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