Trial Outcomes & Findings for Women's Isoflavone Soy Health (WISH) Trial (NCT NCT00118846)

Last Updated: 2023-05-06

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

350 participants

Primary outcome timeframe

Baseline x 2 and then every 6 months, up to 2.5 years

Results posted on

2023-05-06

Participant Flow

Participants were recruited from the general population through media campaigns.

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.

Participant milestones

Participant milestones
Measure	Isoflavone Soy Protein (ISP) Supplementation 25 gm soy protein supplementation administered twice daily in equivalent dosages (12.5 gm)	Placebo Milk protein matching placebo administered twice daily in equivalent dosages
Overall Study STARTED	175	175
Overall Study COMPLETED	162	163
Overall Study NOT COMPLETED	13	12

Reasons for withdrawal

Reasons for withdrawal
Measure	Isoflavone Soy Protein (ISP) Supplementation 25 gm soy protein supplementation administered twice daily in equivalent dosages (12.5 gm)	Placebo Milk protein matching placebo administered twice daily in equivalent dosages
Overall Study Gastrointestinal (GI) intolerance	3	3
Overall Study Started menopausal hormone replacement therapy (HRT)	3	0
Overall Study Physician Decision	1	0
Overall Study Medical condition	2	2
Overall Study Lost to Follow-up	0	2
Overall Study Personal reason	4	5

Baseline Characteristics

Women's Isoflavone Soy Health (WISH) Trial

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Isoflavone Soy Protein (ISP) Supplementation n=162 Participants 25 gm soy protein supplementation administered twice daily in equivalent dosages (12.5 gm)	Placebo n=163 Participants Milk protein matching placebo administered twice daily in equivalent dosages	Total n=325 Participants Total of all reporting groups
Age, Continuous	60.8 years STANDARD_DEVIATION 7.2 • n=5 Participants	60.9 years STANDARD_DEVIATION 6.9 • n=7 Participants	60.9 years STANDARD_DEVIATION 7.1 • n=5 Participants
Sex: Female, Male Female	162 Participants n=5 Participants	163 Participants n=7 Participants	325 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White (non-Hispanic	97 Participants n=5 Participants	110 Participants n=7 Participants	207 Participants n=5 Participants
Race/Ethnicity, Customized Black (non-Hispanic	12 Participants n=5 Participants	10 Participants n=7 Participants	22 Participants n=5 Participants
Race/Ethnicity, Customized Hispanic	31 Participants n=5 Participants	21 Participants n=7 Participants	52 Participants n=5 Participants
Race/Ethnicity, Customized Asian	21 Participants n=5 Participants	22 Participants n=7 Participants	43 Participants n=5 Participants
Race/Ethnicity, Customized Unknown	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	162 Participants n=5 Participants	163 Participants n=7 Participants	325 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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.

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.

Outcome measures

Outcome measures
Measure	Isoflavone Soy Protein (ISP) Supplementation n=162 Participants 25 gm soy protein supplementation administered twice daily in equivalent dosages (12.5 gm)	Placebo n=163 Participants Milk protein matching placebo administered twice daily in equivalent dosages
Progression of Subclinical Atherosclerosis	4.77 um/year Interval 3.39 to 6.16	5.68 um/year Interval 4.3 to 7.06

SECONDARY outcome

Timeframe: Baseline and 2.5 years

Population: Sample size represents the number of participants with analyzable data collected at 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.

Outcome measures

Outcome measures
Measure	Isoflavone Soy Protein (ISP) Supplementation n=154 Participants 25 gm soy protein supplementation administered twice daily in equivalent dosages (12.5 gm)	Placebo n=159 Participants Milk protein matching placebo administered twice daily in equivalent dosages
Change in Neurocognitive Function (Global Cognition)	0.42 units on a scale Standard Error 0.09	0.31 units on a scale Standard Error 0.08

Adverse Events

Isoflavone Soy Protein (ISP) Supplementation

Serious events: 69 serious events

Other events: 162 other events

Deaths: 0 deaths

Placebo

Serious events: 65 serious events

Other events: 163 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Howard N. Hodis, M.D.

Director, Atherosclerosis Research Unit, University of Southern California

Phone: 323-442-1478

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Isoflavone Soy Protein (ISP) Supplementation n=162 participants at risk 25 gm soy protein supplementation administered twice daily in equivalent dosages (12.5 gm)	Placebo n=163 participants at risk Milk protein matching placebo administered twice daily in equivalent dosages
Reproductive system and breast disorders Breast Pain	5.6% 9/162 • Number of events 11 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	1.8% 3/163 • Number of events 3 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
Reproductive system and breast disorders Vaginal Spotting/Bleeding/Discharge	7.4% 12/162 • Number of events 18 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	2.5% 4/163 • Number of events 5 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
Eye disorders Cataract Surgery/Removal	4.9% 8/162 • Number of events 12 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	3.1% 5/163 • Number of events 6 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
Musculoskeletal and connective tissue disorders Fracture	4.3% 7/162 • Number of events 7 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	6.1% 10/163 • Number of events 11 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
General disorders Fall	4.9% 8/162 • Number of events 8 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	6.7% 11/163 • Number of events 11 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
Infections and infestations Cold/Flu	29.0% 47/162 • Number of events 57 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	14.1% 23/163 • Number of events 29 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
General disorders Sinus Condition/Sinusitis/Sinus Headache/Head Congestion	7.4% 12/162 • Number of events 17 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	6.1% 10/163 • Number of events 11 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
General disorders Non-Cardiac Chest Pain	8.0% 13/162 • Number of events 15 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	8.0% 13/163 • Number of events 19 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
Infections and infestations Sore/Irritation/Strep Throat	6.2% 10/162 • Number of events 12 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	1.8% 3/163 • Number of events 3 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
Musculoskeletal and connective tissue disorders Arthritis/Pain	8.0% 13/162 • Number of events 16 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	5.5% 9/163 • Number of events 9 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
Respiratory, thoracic and mediastinal disorders Bronchitis	5.6% 9/162 • Number of events 12 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	4.9% 8/163 • Number of events 8 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
Renal and urinary disorders Urinary Tract Infection	11.7% 19/162 • Number of events 21 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	3.1% 5/163 • Number of events 5 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
Nervous system disorders Headache/Migraine	4.9% 8/162 • Number of events 8 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	3.7% 6/163 • Number of events 6 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
Gastrointestinal disorders Vomiting/Nausea	6.8% 11/162 • Number of events 12 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	3.7% 6/163 • Number of events 8 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
General disorders Lower Extremity/Swelling/Stiffness/Pain/Strain/Injury/Cramps/Itching	9.3% 15/162 • Number of events 16 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	8.0% 13/163 • Number of events 19 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
General disorders Upper Extremity/Swelling/Stiffness/Pain/Strain/Injury/Cramps/Itching	9.9% 16/162 • Number of events 16 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	6.1% 10/163 • Number of events 10 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
Gastrointestinal disorders Diarrhea/Loose Stool	1.2% 2/162 • Number of events 3 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	5.5% 9/163 • Number of events 10 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
Gastrointestinal disorders Constipation	3.7% 6/162 • Number of events 6 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	9.2% 15/163 • Number of events 17 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
Gastrointestinal disorders Abdominal Bloating/Distension/Gas	7.4% 12/162 • Number of events 13 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	9.8% 16/163 • Number of events 20 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.
Musculoskeletal and connective tissue disorders Back Pain/Spasm/Strain/Sprain/Twisted/Hurt/Discomfort	6.2% 10/162 • Number of events 12 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.	4.9% 8/163 • Number of events 9 • Adverse event data were collected for up to 2.5 years for each participant. At each clinic visit, participants were queried about the occurrence of events since their last clinic visit.