AtherosclerosisPhase 2NCT00118846
Women's Isoflavone Soy Health (WISH) Trial
A Phase 2 study testing 25 gm soy protein supplement in people with Atherosclerosis, run by University of Southern California at 1 site in United States.
Trial summary
The purpose of this study is to determine whether soy supplementation can reduce hardening of the arteries and cognitive decline in postmenopausal women. Read more about this study
- Who is it for?
- Ages 30 years and older, women onlyHealthy volunteers can take part
- Conditions the study is for
- Atherosclerosis
- What is being tested?
- 25 gm soy protein supplement
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 350 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Apr 2004to 19 Mar 2009
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 years and older
- Women only
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Postmenopausal, defined as no vaginal bleeding for at least 1 year and serum estradiol level lower than 20 pg/ml
Who cannot join
- 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
Show all 10Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Atherosclerosis Research Unit, University of Southern California
Los Angeles, California, 90033
About this study
Official title: Phytoestrogens and Progression of Atherosclerosis
The purpose of this study is to determine whether soy supplementation can reduce hardening of the arteries and cognitive decline in postmenopausal women.
Read the 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).
- Conditions
- Atherosclerosis
- Being tested
- 25 gm soy protein supplement, Placebo
- 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
- Medical subject headings
- Atherosclerosis, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
25 gm soy protein supplementDietary supplement
25 gm soy protein supplementation administered in equally divided dosage twice daily (12.5 gm)
PlaceboOther
Milk protein administered twice daily
| Study group | Role | What they receive |
|---|---|---|
| Isoflavone Soy Protein (ISP) Supplementation | Active comparator | 25 gm soy protein supplementation administered twice daily in equivalent dosages (12.5 gm) Receives: Dietary Supplement: 25 gm soy protein supplement |
| Placebo | Placebo comparator | Milk protein matching placebo administered twice daily in equivalent dosages Receives: Other: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline x 2 and then every 6 months, up to 2.5 years
Secondary outcomes (1)
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.
Measured: Baseline and 2.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2005 (estimated)
- Study start12 Apr 2004
- Primary completion19 Mar 2009
- Study completion19 Mar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for AtherosclerosisStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 350 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH), Office of Dietary Supplements (ODS), Office of Research on Women's Health (ORWH), Solae, LLC
- Responsible party
- Principal investigator, Howard N. Hodis, M.D., University of Southern California
- Investigators
- Howard N. Hodis, M.D., Principal investigator, Atherosclerosis Research Unit, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00118846
- Sponsor's protocol ID
- U01AT001653
- Other IDs
- U01AT001653, U01AT001653-02S2, U01AT001653-02S4, U01AT001653-02S5
- Status last verified
- Apr 2023
- First submitted
- 7 Jul 2005
- Last updated
- 6 May 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Hodis HN, Mack WJ, Kono N, Azen SP, Shoupe D, Hwang-Levine J, Petitti D, Whitfield-Maxwell L, Yan M, Franke AA, Selzer RH; Women's Isoflavone Soy Health Research Group. Isoflavone soy protein supplementation and atherosclerosis progression in healthy postmenopausal women: a randomized controlled trial. Stroke. 2011 Nov;42(11):3168-75. doi: 10.1161/STROKEAHA.111.620831. Epub 2011 Sep 8.
PubMed 21903957Henderson VW, St John JA, Hodis HN, Kono N, McCleary CA, Franke AA, Mack WJ; WISH Research Group. Long-term soy isoflavone supplementation and cognition in women: a randomized, controlled trial. Neurology. 2012 Jun 5;78(23):1841-8. doi: 10.1212/WNL.0b013e318258f822.
PubMed 22665144Lin F, Pa J, Karim R, Hodis HN, Han SD, Henderson VW, St John JA, Mack WJ. Subclinical carotid artery atherosclerosis and cognitive function in older adults. Alzheimers Res Ther. 2022 May 7;14(1):63. doi: 10.1186/s13195-022-00997-7.
PubMed 35526057Quaas AM, Kono N, Mack WJ, Hodis HN, Felix JC, Paulson RJ, Shoupe D. Effect of isoflavone soy protein supplementation on endometrial thickness, hyperplasia, and endometrial cancer risk in postmenopausal women: a randomized controlled trial. Menopause. 2013 Aug;20(8):840-4. doi: 10.1097/GME.0b013e3182804353.
PubMed 23422867
Study at a glance
From the registry record, last updated by the sponsor on 6 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phytoestrogens and Progression of Atherosclerosis
- ClinicalTrials.gov ID
- NCT00118846
- Acronym / sponsor ID
- U01AT001653
- Conditions
- Atherosclerosis
- Keywords
- Atherosclerosis, Cardiovascular Diseases, Carotid artery intima-media thickness (CIMT), Cognition, Complementary and alternative medicine, Daidzein, Genistein, Glycitein
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 350 participants (actual)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- National Center for Complementary and Integrative Health (NCCIH), Office of Dietary Supplements (ODS), Office of Research on Women's Health (ORWH), Solae, LLC
- Study start
- 12 Apr 2004 (actual)
- Primary completion
- 19 Mar 2009 (actual)
- Study completion
- 19 Mar 2009 (actual)
- First posted
- 12 Jul 2005 (estimated)
- Results
- Posted 6 May 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Isoflavone Soy Protein (ISP) Supplementation | Active comparator | Dietary Supplement: 25 gm soy protein supplement25 gm soy protein supplementation administered twice daily in equivalent dosages (12.5 gm) |
| Placebo | Placebo comparator | Other: PlaceboMilk protein matching placebo administered twice daily in equivalent dosages |
Who may qualify
- Ages
- 30 years and older
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Postmenopausal, defined as no vaginal bleeding for at least 1 year and serum estradiol level lower than 20 pg/ml
Key exclusion criteria (10 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 25 gm soy protein supplement25 gm soy protein supplementation administered in equally divided dosage twice daily (12.5 gm) | Dietary supplement | Isoflavone Soy Protein (ISP) Supplementation |
| PlaceboMilk protein administered twice daily | Other | Placebo |
Primary outcome
Progression of Subclinical Atherosclerosis
Time frame: 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.
1 secondary outcome
Change in Neurocognitive Function (Global Cognition)
Time frame: Baseline and 2.5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 May 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 21903957Hodis HN, Mack WJ, Kono N, Azen SP, Shoupe D, Hwang-Levine J, Petitti D, Whitfield-Maxwell L, Yan M, Franke AA, Selzer RH; Women's Isoflavone Soy Health Research Group. Isoflavone soy protein supplementation and atherosclerosis progression in healthy postmenopausal women: a randomized controlled trial. Stroke. 2011 Nov;42(11):3168-75. doi: 10.1161/STROKEAHA.111.620831. Epub 2011 Sep 8.
- Results publication: PubMed 22665144Henderson VW, St John JA, Hodis HN, Kono N, McCleary CA, Franke AA, Mack WJ; WISH Research Group. Long-term soy isoflavone supplementation and cognition in women: a randomized, controlled trial. Neurology. 2012 Jun 5;78(23):1841-8. doi: 10.1212/WNL.0b013e318258f822.
- Derived from this study: PubMed 35526057Lin F, Pa J, Karim R, Hodis HN, Han SD, Henderson VW, St John JA, Mack WJ. Subclinical carotid artery atherosclerosis and cognitive function in older adults. Alzheimers Res Ther. 2022 May 7;14(1):63. doi: 10.1186/s13195-022-00997-7.
- Derived from this study: PubMed 23422867Quaas AM, Kono N, Mack WJ, Hodis HN, Felix JC, Paulson RJ, Shoupe D. Effect of isoflavone soy protein supplementation on endometrial thickness, hyperplasia, and endometrial cancer risk in postmenopausal women: a randomized controlled trial. Menopause. 2013 Aug;20(8):840-4. doi: 10.1097/GME.0b013e3182804353.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Howard N. Hodis, M.D. principal investigator
Atherosclerosis Research Unit, University of Southern California
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing 25 gm soy protein supplement in people with Atherosclerosis, run by University of Southern California at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 May 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Progression of Subclinical Atherosclerosis (time frame: Baseline x 2 and then every 6 months, up to 2.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00118846, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 May 2023.