Effect of Genistein in Women With Metabolic Syndrome

Metabolic Syndrome Clinical Trial

Official title:

Genistein Use in Postmenopausal Women With Metabolic Syndrome

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00541710
• Other study ID #: RODA-12254
• Secondary ID: 20073XZSR3
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 9, 2007
• Last updated: September 13, 2012
• Start date: October 2007
• Est. completion date: September 2011

Study information

• Verified date: September 2012
• Source: University of Messina
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: September 2011
• Est. primary completion date: January 2011
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 45 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Metabolic Syndrome
• Metabolic Syndrome X
• Syndrome

Intervention

Dietary Supplement:
• genistein
pills of 27 mg, twice per day for 12 months
• placebo
sugar pills twice per day for 12 months

Locations

Country	Name	City	State
Italy	University of Magnia Graecia	Catanzaro
Italy	Azienda Policlinico Universitario, G. Martino	Messina
Italy	University of Palermo	Palermo

Sponsors (2)

Lead Sponsor	Collaborator
University of Messina	Ministry of Education, Universities and Research, Italy

Country where clinical trial is conducted

Italy, 

References & Publications (4)

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. — View 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. — View 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	markers of bone reabsorption: CTX (C-telopeptide of type I collagen ) and of bone formation: bone ALP (Alkaline phosphatase), plus calcaneus ultrasonography variation values		baseline and six months for markers of bone reabsorption, while baseline and 12 months for evaluation of calcaneus ultrasonography variation values	No
Primary	homeostasis model assessment for insulin resistance (HOMA-IR)	HOMA-IR was calculated using the following formula: fasting glucose (mg/dl) X fasting insulin (uIU/ml)/22.5.	change from baseline at 6 and 12 months	No
Secondary	body mass index	The body mass index (BMI) is calculated by dividing the weight measured in kilograms by the square of the height measured in metres [i.e. BMI = Weight (kg)/ Height (m)]2.	baseline, 6 months and 12 months	No
Secondary	Blood pressure	Three seated blood pressure measurements were taken on the right arm with a sphygmomanometer after the participant had been resting for at least 5 min. Blood pressure values were based on the average of the second and third measurements.	basal, 6 and 12 months	No
Secondary	Metabolic variables	Fasting glucose and insulin were measured in serum collected after an overnight fast using routine methods. Total cholesterol, High Density Lipoprotein-Cholesterol (HDL-C), and triglycerides were measured by using a routine enzymatic method, and the Low-Density Lipoprotein Cholesterol (LDL-C) level was calculated by using the Friedewald formula: [Total cholesterol (mg/dL) - High Density Lipoprotein-Cholesterol (HDL-C) (mg/dL) - triglycerides (mg/dL)/5].	basal, 6 and 12 months	No
Secondary	Inflammatory markers	Serum visfatin, adiponectin, and homocysteine were measured by using an immunoenzymatic assay was measured by using an immunoenzymatic assay.	basal, 6 and 12 months	No
Secondary	Adverse events	Participants were asked about symptoms at clinic visits every 6 months. Standard clinical evaluations and laboratory analyses, including hematologic, renal, and liver function tests, were done every 6 months. Endometrial thickness was evaluated by using ultrasonography at baseline, 6 months, and 1 year. The endometrial thickness was measured in the sagittal plane from 1 basal layer to the other. If the endometrial thickness was 8 mm or greater or if uterine bleeding occurred, hysteroscopy and endometrial biopsy were performed. All unfavorable and unintended clinical effects were considered adverse effects and were evaluated for severity, duration, seriousness, and relation to the study drug and outcome.	basal, 6 and 12 months	Yes

External Links

•   Link