Ignite Creation Date:
2024-05-06 @ 11:41 AM
Last Modification Date:
2024-10-26 @ 12:48 PM
Study NCT ID:
NCT03570125
Status:
UNKNOWN
Last Update Posted:
2018-06-28
First Post:
2018-06-11
Brief Title:
BRCA Main Home Nutritional Intervention-random Study
Sponsor:
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
Organization:
Azienda Ospedaliera Universitaria Policlinico Paolo Giaccone Palermo
Study Overview
Official Title:
BRCA Main Home Nutritional Intervention-random Study
Status:
UNKNOWN
Status Verified Date:
2018-06
Last Known Status:
RECRUITING
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Women carrying harmful mutation in BRCA1 or BRCA2 gene are at higher risk to develop breast andor 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 fastingstarvation 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 BRCA12 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 BRCA12 mutations in response to the dietary interventions 1b cancer incidence and progression in genetically engineered mice K14Cre Brca1floxflox Trp53flox and K14Cre Brca1flox 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
Detailed Description:
The risk Women carrying harmful mutation in BRCA1 or BRCA2 gene are at higher risk to develop breast andor ovarian cancer than the general population 12 percent of all US 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 14 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 1019630-643 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 GHIGF1 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 fastingstarvation 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
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 14 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 1019630-643 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 GHIGF1 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 fastingstarvation 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 Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None