BRCA Main Home Nutritional Intervention-random Study

NCT03570125 | Unknown DMC

• 1 other identifier: CEP1:4/2016
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

BRCA1 Mutation; BRCA2 Mutation

Outcome Measures

Primary Outcomes (2)

• IGF1

  IGF1 elisa test

  6 months

• GH

  GH elisa test

  6 months

Study Arms (2)

Dietary intervention arm

EXPERIMENTAL

group will follow an ad libitum diet but, every two months, will follow a 5 day of fasting mimicking diet (PROLON). The diet consists of natural ingredients, which are Generally Regarded As Safe (GRAS). Prolon will be provided for free by L-nutra or in case of unforeseeable budget constraint at one fifth of its commercial value.

Dietary Supplement: Prolon

no intervention

NO INTERVENTION

Control/Placebo with multivitamin supplementation

Interventions

Prolon DIETARY_SUPPLEMENT

The diet consists of natural ingredients, which are Generally Regarded As Safe (GRAS). In case the PROLON product will be unavailable at the time of the project we will design fasting mimicking diet without the usage of specifically designed commercial product

Dietary intervention arm

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• BRCA1 mutation carrier BRCA 2 mutation carrier

You may not qualify if:

• diabetes anorexic under treatment for glycemic control

Sponsors & Collaborators

• Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo: lead

Study Sites (1)

AOUP Paolo Giaccone

Palermo, 90127, Italy

RECRUITING

Related Publications (3)

• Cheng CW, Adams GB, Perin L, Wei M, Zhou X, Lam BS, Da Sacco S, Mirisola M, Quinn DI, Dorff TB, Kopchick JJ, Longo VD. Prolonged fasting reduces IGF-1/PKA to promote hematopoietic-stem-cell-based regeneration and reverse immunosuppression. Cell Stem Cell. 2014 Jun 5;14(6):810-23. doi: 10.1016/j.stem.2014.04.014.

  PMID: 24905167 BACKGROUND

• Brandhorst S, Choi IY, Wei M, Cheng CW, Sedrakyan S, Navarrete G, Dubeau L, Yap LP, Park R, Vinciguerra M, Di Biase S, Mirzaei H, Mirisola MG, Childress P, Ji L, Groshen S, Penna F, Odetti P, Perin L, Conti PS, Ikeno Y, Kennedy BK, Cohen P, Morgan TE, Dorff TB, Longo VD. A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan. Cell Metab. 2015 Jul 7;22(1):86-99. doi: 10.1016/j.cmet.2015.05.012. Epub 2015 Jun 18.

  PMID: 26094889 RESULT

• Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F, Fontana L, Mirisola MG, Guevara-Aguirre J, Wan J, Passarino G, Kennedy BK, Wei M, Cohen P, Crimmins EM, Longo VD. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 2014 Mar 4;19(3):407-17. doi: 10.1016/j.cmet.2014.02.006.

  PMID: 24606898 RESULT

MeSH Terms

Interventions

Gestyl

Central Study Contacts

Mario G Mirisola, PhD

CONTACT

+393287538270; mario.mirisola@unipa.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Full Professor

Study Record Dates

• First Submitted: June 11, 2018
• First Posted: June 26, 2018
• Study Start: June 1, 2018
• Primary Completion: May 31, 2019
• Study Completion: May 31, 2020
• Last Updated: June 28, 2018

Record last verified: 2018-06

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)