Clinical trial NCT00541710: Effect of Genistein in Women With Metabolic Syndrome
Official title: Genistein Use in Postmenopausal Women With Metabolic Syndrome
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Metabolic Syndrome
Keywords: menopause
genistein
pre-diabetes
Lead sponsor: University of Messina
Sponsor class: OTHER
Collaborators: name: Ministry of Education, Universities and Research, Italy
First posted: 2007-10-10
Enrollment: 120
Sex: FEMALE
Minimum age (years): 45
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to determine whether the phytoestrogen genistein is effective in improving bone condition in pre-menopausal and post-menopausal women suffering for osteopenia. Since, during the study the investigators realized that at least 70% of post-menopausal recruited women suffered for metabolic syndrome (MS), we have added only in these women, as secondary outcome measures, the evaluation of markers of cardiovascular risk.

Detailed description: MS prevalence increases after the onset of menopause, because of estrogen deficiency. It is still not clear if menopause itself increases the risk of cardiovascular diseases in al women or only in those that develop MS. Many MS patients that show slight modification in cardiovascular and metabolic parameters are not generally pharmacologically treated since diabetes or alteration in the lipid profile are not evidenced. In this respect it is of importance to develop new therapeutic strategies to prevent and treat MS. Genistein (4,5,7-trihydroxyisoflavone), shown a potentially preventive role on the cardiovascular apparatus in post-menopausal women, may be termed as selective ER modulator (SERM), since it reveals both ER-alpha full agonist and ER-beta partial agonist activity.

The investigators studied whether genistein may represent an efficacious and safe alternative for reducing vascular risk in postmenopausal women with metabolic syndrome. The clinical study was a randomized, double-blind, placebo-controlled study involving 150 patients with metabolic syndrome. After a 4-week stabilization on a standard fat-reduced diet, participants were randomly assigned to receive either phytoestrogen genistein (54 mg/day) or placebo for 6 months. At baseline and following treatment fasting plasma glucose, insulin, insulin resistance (HOMA-IR), lipid concentrations, plasma total homocysteine, leptin, adiponectin and visfatin were measured. Bioimpedentiometric and nutritional analysis, as well as a safety assessment of the endometrium and vagina were also performed.

Eligibility criteria: Inclusion Criteria:

Post-menopausal satus

The presence of three or more of the five following criteria:

waist circumference ≥88 cm; Triglycerides ≥150 mg/dl or on drug treatment for elevated triglycerides; high-density-lipoprotein (HDL) cholesterol \<50 mg/dl or on drug treatment for reduced HDL-C; Fasting glucose ≥100 mg/dl or on drug treatment for elevated glucose; Blood pressure ≥130/85 mmHg or on antihypertensive drug treatment in a subject with a history of hypertension.

Exclusion Criteria:

clinical or laboratory evidence of confounding systemic diseases (e.g., chronic renal or hepatic failure, chronic inflammatory diseases) cardiovascular disease (CVD) defined as documented myocardial infarction, ischaemic heart disease, coronary heart bypass, coronary angioplasty, cerebral thromboembolism, and peripheral amputations, or by Minnesota codes 1°1-3, 4°1-4, 5°1-3 at a standard ECG performed in the 12 months preceding the study; coagulopathy; use of oral or transdermal estrogen, progestin, androgens, selective estrogen receptor modulators, or other steroids; treatment in the preceding six months with polyunsaturated n-3 fatty acids supplements, non steroidal anti-inflammatory drugs (NSAIDs) or steroids, that would interfere with evaluation of the study medication; smoking habit of more than 2 cigarettes daily.

Primary outcomes:
measure: markers of bone reabsorption: CTX (C-telopeptide of type I collagen ) and of bone formation: bone ALP (Alkaline phosphatase), plus calcaneus ultrasonography variation values
timeFrame: baseline and six months for markers of bone reabsorption, while baseline and 12 months for evaluation of calcaneus ultrasonography variation values
measure: homeostasis model assessment for insulin resistance (HOMA-IR)
timeFrame: change from baseline at 6 and 12 months
Secondary outcomes:
measure: body mass index
timeFrame: baseline, 6 months and 12 months
measure: Blood pressure
timeFrame: basal, 6 and 12 months
measure: Metabolic variables
timeFrame: basal, 6 and 12 months
measure: Inflammatory markers
timeFrame: basal, 6 and 12 months
measure: Adverse events
timeFrame: basal, 6 and 12 months
Other outcomes:
Locations:
city: Catanzaro
country: Italy
facility: University of Magnia Graecia
city: Messina
country: Italy
facility: Azienda Policlinico Universitario, G. Martino
city: Palermo
country: Italy
facility: University of Palermo
Study officials:
affiliation: University of Messina, Italy
name: Rosario D'Anna, professor
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Messina
name: Francesco Squadrito, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Marini H, Minutoli L, Polito F, Bitto A, Altavilla D, Atteritano M, Gaudio A, Mazzaferro S, Frisina A, Frisina N, Lubrano C, Bonaiuto M, D'Anna R, Cannata ML, Corrado F, Adamo EB, Wilson S, Squadrito F. Effects of the phytoestrogen genistein on bone metabolism in osteopenic postmenopausal women: a randomized trial. Ann Intern Med. 2007 Jun 19;146(12):839-47. doi: 10.7326/0003-4819-146-12-200706190-00005.
citation: D'Anna R, Cannata ML, Atteritano M, Cancellieri F, Corrado F, Baviera G, Triolo O, Antico F, Gaudio A, Frisina N, Bitto A, Polito F, Minutoli L, Altavilla D, Marini H, Squadrito F. Effects of the phytoestrogen genistein on hot flushes, endometrium, and vaginal epithelium in postmenopausal women: a 1-year randomized, double-blind, placebo-controlled study. Menopause. 2007 Jul-Aug;14(4):648-55. doi: 10.1097/01.gme.0000248708.60698.98.
citation: Crisafulli A, Altavilla D, Squadrito G, Romeo A, Adamo EB, Marini R, Inferrera MA, Marini H, Bitto A, D'Anna R, Corrado F, Bartolone S, Frisina N, Squadrito F. Effects of the phytoestrogen genistein on the circulating soluble receptor activator of nuclear factor kappaB ligand-osteoprotegerin system in early postmenopausal women. J Clin Endocrinol Metab. 2004 Jan;89(1):188-92. doi: 10.1210/jc.2003-030891.
citation: Morabito N, Crisafulli A, Vergara C, Gaudio A, Lasco A, Frisina N, D'Anna R, Corrado F, Pizzoleo MA, Cincotta M, Altavilla D, Ientile R, Squadrito F. Effects of genistein and hormone-replacement therapy on bone loss in early postmenopausal women: a randomized double-blind placebo-controlled study. J Bone Miner Res. 2002 Oct;17(10):1904-12. doi: 10.1359/jbmr.2002.17.10.1904.
citation: Irace C, Marini H, Bitto A, Altavilla D, Polito F, Adamo EB, Arcoraci V, Minutoli L, Di Benedetto A, Di Vieste G, de Gregorio C, Gnasso A, Corrao S, Licata G, Squadrito F. Genistein and endothelial function in postmenopausal women with metabolic syndrome. Eur J Clin Invest. 2013 Oct;43(10):1025-31. doi: 10.1111/eci.12139. Epub 2013 Jul 30.