- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03570125
BRCA Main Home Nutritional Intervention-random Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The risk. Women carrying harmful mutation in BRCA1 or BRCA2 gene are at higher risk to develop breast and/or ovarian cancer than the general population. 12 percent of all U.S. women are going to develop breast cancer sometime during their lives (Howlader N, Noone AM, Krapcho M, et al. (eds). SEER Cancer Statistics Review, 1975-2011, National Cancer Institute.
Bethesda, MD,), while this risk goes up to 65 percent for women who inherit a BRCA1 mutation and 45 percent for those who inherit a BRCA2 mutation by the age of 70 (PMID: 17416853). Similarly, 1.4 percent of women in the general population who will develop ovarian cancer sometime during their lives whereas 39 percent of women who inherit a BRCA1 mutation and 11 to 17 percent of women who inherit a BRCA2 mutation will develop ovarian cancer by age 70 (PMID: 17416853). The risk associated with these mutations is likely to be underestimated since few studies comparing the risk to develop cancer between general population and mutation carriers have been carried out so far. It must be noted that family history of cancer, which specific BRCA1 or BRCA2 mutation has been inherited and reproductive history play a role in cancer risk.
Modifying the risk. Epidemiologists have found a strong association between obesity and the risk of developing breast cancer in postmenopausal women (Ballard-Barbash R, Berrigan D, Potischman N, Dowling E. Obesity and cancer epidemiology. Springer-Verlag New York, LLC, 2010). On the contrary moderate to high physical activity decreases breast cancer risk in both pre and postmenopausal women (Ballard-Barbash R, Hunsberger S, Alciati MH. Journal of the National Cancer Institute 2009; 101(9):630-643.). It is well known that obesity as well as sedentary lifestyle are two significant predictors of development of insulin resistance and Type 2 diabetes mellitus (T2DM) (PMID: 21602457). The molecular mechanisms for these associations are still unknown, but chronic sustained hyperinsulinemia in these insulin-resistant patients appears to play a central role in the carcinogenesis process. Several studies have also shown an increase in breast cancer risk among women who have increased testosterone levels, reduced levels of sex hormone-binding globulin (SHBG), and hence elevated levels of bioavailable androgens and estrogens not bound to SHBG (PMID: 21330633). Collectively, these observations lead to the hypothesis that breast cancer risk may be increased in women with elevated plasma insulin levels. Many studies have related relatively high plasma IGF-I and low IGF binding protein-3 (IGFBP-3) levels with increased risk of breast cancer in pre-menopausal women (PMID: 9593409), prostate cancer in men (PMID: 9438850), colorectal cancer in men and women (PMID: 10203281), and lung cancer in men and women (PMID: 10793110) as well as in angiogenesis, metastasis and in resistance to chemotherapy (PMID: 16931767; PMID: 23098677). Targeting the IGF system is therefore a promising anticancer therapy and a new tool for oncologists (PMID: 16931767).
Inhibition of GH/IGF1 secretion or action decreases the incidence and the rate of progression of cancers in animal studies.
Dwarf mice deficient in growth hormone receptor have lower incidence and delayed occurrence of neoplastic lesions than their wild-type counterpart. In addition, mice with nonfunctioning GHRH receptor and thus very low GH and IGF1 levels, show almost complete inhibition of growth of transplanted human breast cancer cells (PMID: 8603394).
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 insulin-like growth factor 1 (IGF-1) (PMID: 26094889). The Ecuadorian growth hormone receptor deficient cohort, with very low circulating IGF-1 level, show low blood insulin level, higher insulin sensitivity and very low incidence of cancer (PMID: 21325617). Our group has also demonstrated that protein consumption, especially animal proteins, increases IGF1 level and is associated with elevated cancer risk in a US cohort ranging from age 50 to 65 (PMID: 26094889). Finally, evidence is accumulating pointing to Epigenetics as a potential mechanistic link between diet, energy metabolism, and gene expression modulation (PMID: 22152918; PMID: 22444501). The epigenome, even though established at pre-natal level, undergoes several changes throughout the lifetime. The epigenome records a variety of dietary, lifestyle, behavioral, and social cues, providing thus an interface between the environment and the genome.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Mario G Mirisola, PhD
- Phone Number: +393287538270
- Email: mario.mirisola@unipa.it
Study Locations
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-
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Palermo, Italy, 90127
- Recruiting
- AOUP Paolo Giaccone
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Contact:
- Mario G Mirisola, PhD
- Phone Number: +393287538270
- Email: mario.mirisola@unipa.it
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
BRCA1 mutation carrier BRCA 2 mutation carrier
Exclusion Criteria:
diabetes anorexic under treatment for glycemic control
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Prevention
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Dietary intervention arm
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. |
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
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No Intervention: no intervention
Control/Placebo with multivitamin supplementation
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
IGF1
Time Frame: 6 months
|
IGF1 elisa test
|
6 months
|
GH
Time Frame: 6 months
|
GH elisa test
|
6 months
|
Collaborators and Investigators
Publications and helpful links
General Publications
- 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. Erratum In: Cell Stem Cell. 2016 Feb 4;18(2):291-2.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- CEP1:4/2016
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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