Effect of Genistein in Women With Metabolic Syndrome

This study has been completed.
Sponsor:
Collaborator:
Ministry of Education, Universities and Research, Italy
Information provided by (Responsible Party):
Rosario D'anna, University of Messina
ClinicalTrials.gov Identifier:
NCT00541710
First received: October 9, 2007
Last updated: September 13, 2012
Last verified: September 2012
  Purpose

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.


Condition Intervention Phase
Metabolic Syndrome
Dietary Supplement: genistein
Dietary Supplement: placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Genistein Use in Postmenopausal Women With Metabolic Syndrome

Resource links provided by NLM:


Further study details as provided by University of Messina:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]
  • homeostasis model assessment for insulin resistance (HOMA-IR) [ Time Frame: change from baseline at 6 and 12 months ] [ Designated as safety issue: No ]
    HOMA-IR was calculated using the following formula: fasting glucose (mg/dl) X fasting insulin (uIU/ml)/22.5.


Secondary Outcome Measures:
  • body mass index [ Time Frame: baseline, 6 months and 12 months ] [ Designated as safety issue: No ]
    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.

  • Blood pressure [ Time Frame: basal, 6 and 12 months ] [ Designated as safety issue: No ]
    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.

  • Metabolic variables [ Time Frame: basal, 6 and 12 months ] [ Designated as safety issue: No ]
    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].

  • Inflammatory markers [ Time Frame: basal, 6 and 12 months ] [ Designated as safety issue: No ]
    Serum visfatin, adiponectin, and homocysteine were measured by using an immunoenzymatic assay was measured by using an immunoenzymatic assay.

  • Adverse events [ Time Frame: basal, 6 and 12 months ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 120
Study Start Date: October 2007
Study Completion Date: September 2011
Primary Completion Date: January 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Dietary Supplement: genistein
pills of 27 mg, twice per day for 12 months
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.
Dietary Supplement: placebo
sugar pills twice per day for 12 months

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

Ages Eligible for Study:   45 Years to 70 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00541710

Locations
Italy
University of Magnia Graecia
Catanzaro, Italy
Azienda Policlinico Universitario, G. Martino
Messina, Italy, 090
University of Palermo
Palermo, Italy, 90129
Sponsors and Collaborators
University of Messina
Ministry of Education, Universities and Research, Italy
Investigators
Principal Investigator: Rosario D'Anna, professor University of Messina, Italy
Principal Investigator: Francesco Squadrito, MD University of Messina
  More Information

Additional Information:
Publications:
Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Rosario D'anna, Associate Professor, University of Messina
ClinicalTrials.gov Identifier: NCT00541710     History of Changes
Other Study ID Numbers: RODA-12254, 20073XZSR3
Study First Received: October 9, 2007
Last Updated: September 13, 2012
Health Authority: Italy: Ethics Committee

Keywords provided by University of Messina:
menopause
genistein
pre-diabetes

Additional relevant MeSH terms:
Metabolic Syndrome X
Syndrome
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Disease
Pathologic Processes
Genistein
Anticarcinogenic Agents
Protective Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Phytoestrogens
Estrogens, Non-Steroidal
Estrogens
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on October 16, 2014