List of Clinical Trials

Safety, feasibility and metabolic effects of the Fasting Mimicking Diet (FMD) in cancer patients. (NCT03340935)

Impact of dietary intervention on tumor immunity: The digest trial (digest) (NCT03454282)

Status:
Ongoing

Participants:
FMD in breast cancer and melanoma / 100 participants

Study:
Interventional Single Group Assignment (May 24, 2018-May 30, 2020)

Location:
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy

Researcher:
Filippo De Braud, Claudio Vernieri, MD (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.

Os-10-3 a randomized, phase ll clinical trial of a controlled diet prior to selected chemotherapy treatment in breast and prostate cancer, to evaluate the impact on toxicity and efficacy. (NCT01802346)

Status:
Ongoing

Participants:
Chemolieve in breast and prostate cancer / 120 participants (60 patients for breast and 60 patients for prostate cancer)

Study:
Interventional, Parallel Assignment
(January 29, 2013 – January 29, 2019   (Final data collection date for primary outcome measure))
Estimated Study Completion Date : January 29, 2020

Location:
University Of Southern California, Los Angeles, 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.

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 study (Starting date: November 2017)

Location:
University of Genova, Italy

Researcher:
Prof. Alessio Nencioni, MD (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.

BRCA mainhome 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

Study:
Randomized pilot study

Location:
University Hospital, “Policlinico Paolo Giaccone” of Palermo, Italy.

Researcher:
Prof. Giovanni Mirisola (mario.mirisola@unipa.it)

Synopsis

It is planned to verify if the fasting mimicking diet (FMD) is able to modify some haematological parameters that predict the risk of cancer. Follow-up will evaluate the variation of the risk of tumor onset.

Short-term fasting prior to platinum-based chemotherapy: Feasibility and impact on toxicity

Status:
Ongoing

Study:
Fasting trial

Location:
University Of Southern California, Los Angeles, in collaboration with Norris Cancer Center and LAC+USC

Researcher:
Prof. Giovanni Mirisola (mario.mirisola@unipa.it)

Synopsis

1. To determine the safety and feasibility of short-term fasting prior to administration of combination chemotherapy with platinum in patients with advanced solid tumor malignancies.
2. To evaluate the toxicity profile of platinum-based chemotherapy in subjects who eat normally compared to those who undertake short-term starvation
3. we hypothesize that fasting will reduce the incidence of significant toxicities (see definition in section X) at any time during 2 cycles of chemotherapy by 25% (from 90% to 65%)

C. To investigate changes in plasma insulin, glucose, IGF1 and IGF binding protein (IGFBP) levels, and oxidative stress markers in subjects who undertake short-term fasting compared to controls.

Neoadjuvant chemotherapy for her2 negative breast cancer (direct) (NCT02126449)

Status:
Completed

Participants:
FMD and Breast Cancer / 131 participants

Study:
Interventional randomized, Parallel Assignment
(February 2014 – December 2018 – December 2019)

Location:
Leiden, The Netherlands

Researcher:

Judith R Kroep, MD, PhD +31715263464

j.r.kroep@lumc.nl

Contact: 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.

Fasting and nutritional therapy in patients with advanced metastatic prostate cancer (NCT02710721)

Status:
Ongoing

Participants:
Fasting and advanced metastatic prostate cancer / 60 participants

Study:
Interventional, Parallel Assignment
(April 2016 – December 2018   (Final data collection date for primary outcome measure) Estimated Study Completion Date: December 2019)

Location:
Charite University, Berlin, Germany

Researcher:

Ursula Steiner, Dr.   +49 30 8445 2577
ursula.steiner@charite.de.

Kurt Miller, Prof. Dr.   +49 30 8445 2575
kurt.miller@charite.de. Principal Investigator: Kurt Miller

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.

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

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 CancerInstitute (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.

The effects of short-term fasting on tolerance to (NEO) adjuvant chemotherapy in her2-negative breast cancer patients: A randomized pilot study (NCT01304251)

Status:
Completed

Participants:
Fasting and Chemotherapy in HER2- negative breast cancer / 13 patients

Study:
Randomized pilot study

Location:
Leiden, The Netherlands

Researcher:
Judith R Kroep, MD, PhD

+31715263464

j.r.kroep@lumc.nl

Contact: Stefanie de Groot, MD

+31715263464

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.

Background

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, March 2011

Safety and feasibility of fasting in combination with platinum-based chemotherapy (NCT00936364)

Status:
Completed

Participants:
Fasting before chemotherapy / 20 patients

Study:
Clinical trial

Location:
University of Southern California, Los Angeles, in collaboration with Norris Cancer Center

Researcher:
Valter Longo and 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.

Background

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 on ging randomized trial is studying the effect of 72 h of fasting.

Trial registration: NCT00936364, registered propectively on July 9, 2009.

Short-term fasting during chemotherapy in patients with gynecological cancer- a randomized controlled cross-over trial (fit) (NCT01954836)

Status:
Completed

Participants:
FMD and gynecological cancer / 50 participants

Study:
Randomized Crossover Assignment

Location:
Charite University, Berlin, Germany

Researcher:
Andreas Michalsen

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.

Background

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.

Fasting-mimicking diet in patients receiving chemo-immunotherapy for treatment of metastatic non-small cell lung cancer

Status:
Planned

Participants:
FMD and lung cancer / 40 patients

Study:
Randomized clinical trial

Location:
Indiana University Melvin and Bren Simon Cancer Center

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.

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, 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-day fasting-mimicking diet within two months). Study endpoints will include muscular strength evaluation of lower limbs, cardio-pulmonary responses, neuromuscular function and muscle architecture.

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, cross-over

Location:
Sapienza University, Rome, Italy

Researcher:
Prof. Alessandro Laviano (alessandro.laviano@uniroma1.it)

Synopsis

Primary endpoint:

1. 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:

1. 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).
   
   
2. 3.Evaluate the systemic effects of the use of FMD on the cognitive component.
3.  
4. 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.

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 & Hashimoto’s Thyroiditis / 60 patients + 60 controls

Study:
Randomized Pilot Study

Location:
Regenerative Medicine Center, Pittsburg Pennsylvania

Researcher:
Valerie Donaldson, MD

Synopsis

We will conduct a randomizied pilot study to investigate the effect of the ProLon diet on auotimmune and inflammatory status in Hashimoto’s thyroiditis treatment in an adult population (18-70 years) 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-day 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.

Randomized phase i / ii study of a hypoproteic diet in patients with cognitive impairment

Status:
Planned

Participants:
PROLON + SUPPLEMENT AD AND AD OR MCI / 60 patients affected by mild AD (MMSE 18-23) and 60 patients affected by MCI

Study:
Phase I/II Randomized clinical trial

Location:
Genova, Italy. University of Genova

Researcher:
Prof. Patrizio Odetti (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 neurorigenerative 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.

Multiple Sclerosis

Status:
Planned

Participants:
ProLon Multiple Sclerosis

Study:
Randomized clinical trial

Location:
Genova, Italy

Researcher:
Prof. Gianluigi Mancardi (glmancardi@neurologia.unige.it)

Primary Objective:

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

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:

Safety and feasibility of fasting in combination with platinum-based chemotherapy (NCT00936364)

Status:
Completed

Participants:
Fasting before chemotherapy / 20 patients

Study:
Clinical trial

Location:
University of Southern California, Los Angeles, in collaboration with Norris Cancer Center

Researcher:
Valter Longo and 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.

Background

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 on ging randomized trial is studying the effect of 72 h of fasting.

Trial registration: NCT00936364, registered propectively on July 9, 2009.

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, in collaboration with USC Norris Keck Hospital

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 a six months follow up, and will be assessed for metabolic risk factor, metabolic profile, life quality and general health throughout the study.

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:

Location:
University of Southern California, Los Angeles, 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.

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:

Study:

Location:
University of Southern California, Los Angeles, 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.

5 MEALS A DAY VS 2 MEALS A DAY: To Evaluate the consumption of two meals plus one snack per day compare to 5 meals per day on initial weigh loss and weight maintenance over the period of 12 months in overweight and obese individuals with (BMI >27).

Status:
Planned

Participants:

Study:

Location:
University of Southern California, Los Angeles, in collaboration with USC Norris Keck Hospital

Researcher:

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.