Atherosclerosis
Conditions
Keywords
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, Soy Protein, Subclinical Vascular Disease, Ultrasonography, Women
Brief summary
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
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).
Interventions
DIETARY_SUPPLEMENT25 gm soy protein supplement
25 gm soy protein supplementation administered in equally divided dosage twice daily (12.5 gm)
OTHERPlacebo
Milk protein administered twice daily
Sponsors
National Center for Complementary and Integrative Health (NCCIH)
Office of Dietary Supplements (ODS)
Office of Research on Women's Health (ORWH)
Solae, LLC
University of Southern California
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
30 Years to No maximum
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression of Subclinical Atherosclerosis | Baseline x 2 and then every 6 months, up to 2.5 years | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Neurocognitive Function (Global Cognition) | Baseline and 2.5 years | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the general population through media campaigns.
Pre-assignment details
1063 individuals were assessed for eligibility. 713 were not enrolled (660 did not meet inclusion criteria; 53 were eligible but declined to participate). 350 individuals were randomized.
Participants by arm
| Arm | Count |
|---|---|
| Isoflavone Soy Protein (ISP) Supplementation 25 gm soy protein supplementation administered twice daily in equivalent dosages (12.5 gm) | 162 |
| Placebo Milk protein matching placebo administered twice daily in equivalent dosages | 163 |
| Total | 325 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Gastrointestinal (GI) intolerance | 3 | 3 |
| Overall Study | Lost to Follow-up | 0 | 2 |
| Overall Study | Medical condition | 2 | 2 |
| Overall Study | Personal reason | 4 | 5 |
| Overall Study | Physician Decision | 1 | 0 |
| Overall Study | Started menopausal hormone replacement therapy (HRT) | 3 | 0 |
Baseline characteristics
| Characteristic | Total | Isoflavone Soy Protein (ISP) Supplementation | Placebo |
|---|---|---|---|
| Age, Continuous | 60.9 years STANDARD_DEVIATION 7.1 | 60.8 years STANDARD_DEVIATION 7.2 | 60.9 years STANDARD_DEVIATION 6.9 |
| Race/Ethnicity, Customized Asian | 43 Participants | 21 Participants | 22 Participants |
| Race/Ethnicity, Customized Black (non-Hispanic | 22 Participants | 12 Participants | 10 Participants |
| Race/Ethnicity, Customized Hispanic | 52 Participants | 31 Participants | 21 Participants |
| Race/Ethnicity, Customized Unknown | 1 Participants | 1 Participants | 0 Participants |
| Race/Ethnicity, Customized White (non-Hispanic | 207 Participants | 97 Participants | 110 Participants |
| Region of Enrollment United States | 325 Participants | 162 Participants | 163 Participants |
| Sex: Female, Male Female | 325 Participants | 162 Participants | 163 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 162 | 0 / 163 |
| other Total, other adverse events | 162 / 162 | 163 / 163 |
| serious Total, serious adverse events | 69 / 162 | 65 / 163 |
Outcome results
Primary
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.
Time frame: Baseline x 2 and then every 6 months, up to 2.5 years
Population: Rate of change in distal common carotid artery (CCA) far wall intima-media thickness (um per year) in computer image processed B-mode ultrasonograms.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Isoflavone Soy Protein (ISP) Supplementation | Progression of Subclinical Atherosclerosis | 4.77 um/year |
| Placebo | Progression of Subclinical Atherosclerosis | 5.68 um/year |
p-value: 0.3595% CI: [-2.86, 1.05]Mixed Models Analysis
Secondary
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.
Time frame: Baseline and 2.5 years
Population: Sample size represents the number of participants with analyzable data collected at baseline and 2.5 years.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Isoflavone Soy Protein (ISP) Supplementation | Change in Neurocognitive Function (Global Cognition) | 0.42 units on a scale | Standard Error 0.09 |
| Placebo | Change in Neurocognitive Function (Global Cognition) | 0.31 units on a scale | Standard Error 0.08 |
p-value: 0.3695% CI: [-0.13, 0.35]ANCOVA