- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00541710
Effect of Genistein in Women With Metabolic Syndrome
Genistein Use in Postmenopausal Women With Metabolic Syndrome
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
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Catanzaro, Italy
- University of Magnia Graecia
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Messina, Italy, 090
- Azienda Policlinico Universitario, G. Martino
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Palermo, Italy, 90129
- University of Palermo
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Placebo Comparator: Lifestyle counseling
Placebo tablets.
All participants were counseled on an moderate hypocaloric, Mediterranean-style diet composed of 25% to 30% energy from fat, less than 10% energy from saturated fatty acids, 55% to 60% energy from carbohydrates, and 15% energy from protein, with a cholesterol intake less than 300 mg/d and fiber intake of 35 g/d or greater.
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pills of 27 mg, twice per day for 12 months
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Experimental: Genistein
Genistein 54 mg/day in 2 tablets for 12 months.
All participants were counseled on an moderate hypocaloric, Mediterranean-style diet composed of 25% to 30% energy from fat, less than 10% energy from saturated fatty acids, 55% to 60% energy from carbohydrates, and 15% energy from protein, with a cholesterol intake less than 300 mg/d and fiber intake of 35 g/d or greater.
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sugar pills twice per day for 12 months
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
markers of bone reabsorption: CTX (C-telopeptide of type I collagen ) and of bone formation: bone ALP (Alkaline phosphatase), plus calcaneus ultrasonography variation values
Time Frame: baseline and six months for markers of bone reabsorption, while baseline and 12 months for evaluation of calcaneus ultrasonography variation values
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baseline and six months for markers of bone reabsorption, while baseline and 12 months for evaluation of calcaneus ultrasonography variation values
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homeostasis model assessment for insulin resistance (HOMA-IR)
Time Frame: change from baseline at 6 and 12 months
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HOMA-IR was calculated using the following formula: fasting glucose (mg/dl) X fasting insulin (uIU/ml)/22.5.
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change from baseline at 6 and 12 months
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
body mass index
Time Frame: baseline, 6 months and 12 months
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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.
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baseline, 6 months and 12 months
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Blood pressure
Time Frame: basal, 6 and 12 months
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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.
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basal, 6 and 12 months
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Metabolic variables
Time Frame: basal, 6 and 12 months
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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].
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basal, 6 and 12 months
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Inflammatory markers
Time Frame: basal, 6 and 12 months
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Serum visfatin, adiponectin, and homocysteine were measured by using an immunoenzymatic assay was measured by using an immunoenzymatic assay.
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basal, 6 and 12 months
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Adverse events
Time Frame: basal, 6 and 12 months
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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.
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basal, 6 and 12 months
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Rosario D'Anna, professor, University of Messina, Italy
- Principal Investigator: Francesco Squadrito, MD, University of Messina
Publications and helpful links
General Publications
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Glucose Metabolism Disorders
- Metabolic Diseases
- Disease
- Insulin Resistance
- Hyperinsulinism
- Syndrome
- Metabolic Syndrome
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Hormones
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Protective Agents
- Estrogens, Non-Steroidal
- Estrogens
- Protein Kinase Inhibitors
- Anticarcinogenic Agents
- Phytoestrogens
- Genistein
Other Study ID Numbers
- RODA-12254
- 20073XZSR3 (Other Grant/Funding Number: MIUR Italian Ministry of Research)
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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