Women's Isoflavone Soy Health (WISH) Trial

Study Overview
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Brief Summary
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The purpose of this study is to determine whether soy supplementation can reduce hardening of the arteries and cognitive decline in postmenopausal women.

Detailed Description
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Heart disease is the leading cause of death among women in the United States. Atherosclerosis, a primary cause of heart disease, accounts for more than 485,000 heart attacks and 370,000 strokes each year in American women. Data indicate that a woman's risk of suffering from an atherosclerosis-related cardiovascular event significantly increases after menopause; this risk may be due to reduced estrogen production associated with menopause. Soy isoflavones are plant compounds that are structurally similar to human estrogen. Evidence suggests that soy supplements may provide the same protection against heart disease as estrogen in postmenopausal women. This study will determine the effects of soy supplementation on subclinical atherosclerosis progression and cognitive decline in postmenopausal women. In this double-blinded, placebo-controlled trial, a total of 350 postmenopausal women were randomly assigned to receive either soy protein supplementation or placebo twice daily for 2.7 years. The initial 2.5-year treatment period was increased to 3 years. The active product, given as two divided doses, was 25 g soy protein containing 85 mg aglycone weight naturally-occurring isoflavones (150 mg total isoflavone) of genistein 45 mg aglycone weight (80 mg total weight), daidzein 35 mg aglycone weight (60 mg total weight), and glycitein 5 mg aglycone weight (10 mg total weight). The primary trial end point was the rate of change in the right distal common carotid artery intima-media thickness (CIMT) by ultrasonography. Participants underwent ultrasonography at baseline and every six months along with laboratory determinations and clinical measurements. Cognitive assessments were completed at baseline and the final follow-up visit (2.5 years).

Official Title
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Phytoestrogens and Progression of Atherosclerosis

Conditions
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Atherosclerosis

Intervention / Treatment
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* Dietary Supplement: 25 gm soy protein supplement
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Postmenopausal, defined as no vaginal bleeding for at least 1 year and serum estradiol level lower than 20 pg/ml Exclusion Criteria: Signs, symptoms or personal history of cardiovascular disease Diabetes mellitus or fasting serum glucose of 126 mg/dL or greater Fasting plasma triglyceride of 500 mg/dL or greater Serum creatinine greater than 2.0 mg/dL Uncontrolled hypertension Untreated thyroid disease Life expectancy less than 5 years Current use of hormone replacement therapy (HRT) Soy, nut, or related food allergies More than 5 alcohol drinks per day or substance abuse

Ages Eligible for Study
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Minimum Age: 30 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Isoflavone Soy Protein (ISP) Supplementation<br>25 gm soy protein supplementation administered twice daily in equivalent dosages (12.5 gm) | Dietary Supplement: 25 gm soy protein supplement<br>* 25 gm soy protein supplementation administered in equally divided dosage twice daily (12.5 gm)<br>|
| Placebo Comparator: Placebo<br>Milk protein matching placebo administered twice daily in equivalent dosages | Other: Placebo<br>* Milk protein administered twice daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression of Subclinical Atherosclerosis | Rate of change in right distal common carotid artery (CCA) far wall intima-media thickness (um per year) in computer image processed B-mode ultrasonograms. | Baseline x 2 and then every 6 months, up to 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Neurocognitive Function (Global Cognition) | The specified primary cognitive endpoint compared between treatment groups was change from baseline on a global cognitive composite score calculated as an average of standardized scores for 14 neuropsychological tests weighted by the inverse intertest correlation matrix. Neuropsychological test scores at baseline and follow-up assessments were standardized ([raw score-mean score]/standard deviation) using the baseline means and standard deviations from the entire WISH sample. Each of 3 cognitive composite scores was calculated at baseline and follow-up as the weighted average of the individual donor standardized test scores weighted by the inverse correlation among tests. Change from baseline (endpoint minus baseline cognitive outcome) was computed for each cognitive score (verbal memory, global cognition, executive function). Since the outcome is not a single test but a weighted average of multiple tests, the range is not standardized and there are no established clinical thresholds. | Baseline and 2.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Soy, Atherosclerosis, Cardiovascular Diseases, Carotid artery intima-media thickness (CIMT), Cognition, Complementary and alternative medicine, Daidzein, Genistein, Glycitein, Intervention, Isoflavones, Menopause, Prevention, Postmenopausal, Randomized controlled study, Soy Protein, Subclinical Vascular Disease, Ultrasonography, Women