Clinical trial NCT00118846: Women's Isoflavone Soy Health (WISH) Trial
Official title: Phytoestrogens and Progression of Atherosclerosis
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Atherosclerosis
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
Lead sponsor: University of Southern California
Sponsor class: OTHER
Collaborators: name: National Center for Complementary and Integrative Health (NCCIH)
name: Office of Dietary Supplements (ODS)
name: Office of Research on Women's Health (ORWH)
name: Solae, LLC
First posted: 2005-07-12
Enrollment: 350
Sex: FEMALE
Minimum age (years): 30
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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).

Eligibility criteria: 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

Primary outcomes:
measure: Progression of Subclinical Atherosclerosis
timeFrame: Baseline x 2 and then every 6 months, up to 2.5 years
Secondary outcomes:
measure: Change in Neurocognitive Function (Global Cognition)
timeFrame: Baseline and 2.5 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Atherosclerosis Research Unit, University of Southern California
state: California
Study officials:
affiliation: Atherosclerosis Research Unit, University of Southern California
name: Howard N. Hodis, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: Henderson 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.
citation: Lin 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.
citation: Quaas 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.