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Effects of Genistein in Postmenopausal Women With Metabolic Syndrome

Primary Purpose

Metabolic Syndrome

Status
Completed
Phase
Phase 2
Locations
Italy
Study Type
Interventional
Intervention
Genistein
Placebo
Sponsored by
University of Messina
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metabolic Syndrome focused on measuring menopause, pre-diabetes

Eligibility Criteria

49 Years - 67 Years (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Post-menopausal satus

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

    1. waist circumference ≥88 cm;
    2. Triglycerides ≥150 mg/dl or on drug treatment for elevated triglycerides;
    3. high-density-lipoprotein (HDL) cholesterol <50 mg/dl or on drug treatment for reduced HDL-C;
    4. Fasting glucose ≥100 mg/dl or on drug treatment for elevated glucose;
    5. 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.

Sites / Locations

  • University of Magnia Graecia
  • University of Messina
  • University of Palermo

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Lifestyle counseling

Genistein

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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].
Inflammatory markers
Serum visfatin, adiponectin, and homocysteine were measured by using an immunoenzymatic assay was measured by using an immunoenzymatic assay.
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.

Full Information

First Posted
August 7, 2012
Last Updated
August 9, 2012
Sponsor
University of Messina
Collaborators
Ministry of Education, Universities and Research, Italy
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1. Study Identification

Unique Protocol Identification Number
NCT01664650
Brief Title
Effects of Genistein in Postmenopausal Women With Metabolic Syndrome
Official Title
Role of Genistein on Metabolic Syndrome in Post-menopausal Women
Study Type
Interventional

2. Study Status

Record Verification Date
August 2012
Overall Recruitment Status
Completed
Study Start Date
September 2008 (undefined)
Primary Completion Date
November 2010 (Actual)
Study Completion Date
January 2011 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
University of Messina
Collaborators
Ministry of Education, Universities and Research, Italy

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
The 15-25% of the population of developed countries suffers for metabolic syndrome. It is associated with a 2-4 fold increase in cardiovascular morbility and mortality and with a 5- 9 fold increase in developing type II diabetes. 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.
Detailed Description
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metabolic Syndrome
Keywords
menopause, pre-diabetes

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
120 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Lifestyle counseling
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Genistein
Arm Type
Experimental
Arm Description
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.
Intervention Type
Dietary Supplement
Intervention Name(s)
Genistein
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Primary Outcome Measure Information:
Title
homeostasis model assessment for insulin resistance (HOMA-IR)
Description
HOMA-IR was calculated using the following formula: fasting glucose (mg/dl) X fasting insulin (uIU/ml)/22.5.
Time Frame
change from baseline at 6 and 12 months
Secondary Outcome Measure Information:
Title
body mass index
Description
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.
Time Frame
basal, 6 and 12 months
Title
Blood pressure
Description
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.
Time Frame
basal, 6 and 12 months
Title
Metabolic variables
Description
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].
Time Frame
basal, 6 and 12 months
Title
Inflammatory markers
Description
Serum visfatin, adiponectin, and homocysteine were measured by using an immunoenzymatic assay was measured by using an immunoenzymatic assay.
Time Frame
basal, 6 and 12 months
Title
Adverse events
Description
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.
Time Frame
basal, 6 and 12 months

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
49 Years
Maximum Age & Unit of Time
67 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Francesco Squadrito, MD
Organizational Affiliation
University of Messina
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Magnia Graecia
City
Catanzaro
Country
Italy
Facility Name
University of Messina
City
Messina
ZIP/Postal Code
98123
Country
Italy
Facility Name
University of Palermo
City
Palermo
ZIP/Postal Code
90129
Country
Italy

12. IPD Sharing Statement

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Effects of Genistein in Postmenopausal Women With Metabolic Syndrome

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