Trial Outcomes & Findings for Alzheimer's Disease: Potential Benefit of Isoflavones (NCT NCT00205179)

NCT ID: NCT00205179

Last Updated: 2020-01-22

Results Overview

Participants are given 1 min to produce as many unique words as possible within a category (category fluency). More words per minute will correlates to better category fluency

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 72 participants
• Primary outcome timeframe: 6 months
• Results posted on: 2020-01-22

Participant Flow

4 subjects withdrew consent; 3 subjects ineligible due to abnormal laboratory tests or inability to complete testing

Participant milestones

Measure	Novasoy 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones	Placebo 100mg/day matching placebo Placebo: 100mg/day matching placebo
Overall Study STARTED	32	33
Overall Study COMPLETED	30	29
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Measure	Novasoy 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones	Placebo 100mg/day matching placebo Placebo: 100mg/day matching placebo
Overall Study Death	0	2
Overall Study Physician Decision	1	1
Overall Study Adverse Event	1	1

Baseline Characteristics

One subject in each group declined to undergo ApoE genotyping

Baseline characteristics by cohort

Measure	Placebo n=33 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=32 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones	Total n=65 Participants Total of all reporting groups
Age, Continuous	76.8 years STANDARD_DEVIATION 6.8 • n=33 Participants	75.7 years STANDARD_DEVIATION 7.7 • n=32 Participants	76 years STANDARD_DEVIATION 7 • n=65 Participants
Sex: Female, Male Female	17 Participants n=33 Participants	17 Participants n=32 Participants	34 Participants n=65 Participants
Sex: Female, Male Male	16 Participants n=33 Participants	15 Participants n=32 Participants	31 Participants n=65 Participants
Race/Ethnicity, Customized White	33 participants n=33 Participants	31 participants n=32 Participants	64 participants n=65 Participants
Race/Ethnicity, Customized Latino	0 participants n=33 Participants	1 participants n=32 Participants	1 participants n=65 Participants
Region of Enrollment United States	33 participants n=33 Participants	32 participants n=32 Participants	65 participants n=65 Participants
Number of participants with Apolipoprotein E4 (ApoE4) allele	15 Participants n=32 Participants • One subject in each group declined to undergo ApoE genotyping	16 Participants n=31 Participants • One subject in each group declined to undergo ApoE genotyping	31 Participants n=63 Participants • One subject in each group declined to undergo ApoE genotyping
Education in years	14.2 years STANDARD_DEVIATION 2.5 • n=33 Participants	14.8 years STANDARD_DEVIATION 2.7 • n=32 Participants	14.5 years STANDARD_DEVIATION 2.6 • n=65 Participants
Total weekly isoflavone intake at Baseline	6.5 mg/week STANDARD_DEVIATION 34.1 • n=33 Participants	16.5 mg/week STANDARD_DEVIATION 66.3 • n=32 Participants	12.5 mg/week STANDARD_DEVIATION 45.2 • n=65 Participants
Global cognition: Mini-Mental State Examination score	22.4 score on a scale STANDARD_DEVIATION 5.3 • n=33 Participants	23.5 score on a scale STANDARD_DEVIATION 4.0 • n=32 Participants	22.95 score on a scale STANDARD_DEVIATION 4.65 • n=65 Participants
Mood symptoms: Geriatric Depression Scale-Short Form score	2.6 score on scale STANDARD_DEVIATION 2.4 • n=33 Participants	3.2 score on scale STANDARD_DEVIATION 3.3 • n=32 Participants	2.9 score on scale STANDARD_DEVIATION 2.85 • n=65 Participants
Number of participants on Acetylcholinesterase-Inhibitors (AchE-I)	30 Participants n=33 Participants	31 Participants n=32 Participants	61 Participants n=65 Participants
Number of participants on N-methyl-D-aspartate receptor (NMDAR) blocker-Memantine	14 Participants n=33 Participants	16 Participants n=32 Participants	30 Participants n=65 Participants
Body Mass Index	27.9 kg/m^2 STANDARD_DEVIATION 5.4 • n=33 Participants	27.5 kg/m^2 STANDARD_DEVIATION 5.0 • n=32 Participants	27.7 kg/m^2 STANDARD_DEVIATION 5.2 • n=65 Participants

PRIMARY outcome

Timeframe: 6 months

Participants are given 1 min to produce as many unique words as possible within a category (category fluency). More words per minute will correlates to better category fluency

Outcome measures

Measure	Placebo n=28 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=27 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Cognitive Outcomes - Language Executive Function : Category Fluency Assessed as Number of Words Generated/Min	21.5 number of words generated per minute Standard Error 1.9	25.7 number of words generated per minute Standard Error 2.0

PRIMARY outcome

Timeframe: 6 months

Participants are given 1 min to produce as many words as possible starting with a given letter (letter fluency). More number of words per minute correlates to better phonemic fluency/verbal fluency

Outcome measures

Measure	Placebo n=28 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=28 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Cognitive Outcomes - Language Executive Function : Phonemic Fluency/Verbal Fluency Assessed as Number of Words Generated Per Minute	25.9 number of words generated per minute Standard Error 2.4	35.2 number of words generated per minute Standard Error 2.4

PRIMARY outcome

Timeframe: 6 months

List of 15 semantically unrelated words is presented verbally to the participants once, after which they are asked to free recall as many words as possible. Subsequently, this presentation-test routine (learning trials) is repeated four more times. A total recall score is determined by adding the number of recalled items for the five learning trials. After presentation of a distractor list and a delay of approximately 20 minutes, participants are asked to freely recall items from the original word list. A delayed recall score is then derived from this test.

Outcome measures

Measure	Placebo n=29 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=28 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Immediate and Delayed Recall on Verbal Memory/ List Learning Immediate and Delayed Free Recall: Number of Words Recalled	1.8 Number of words recalled Standard Error 0.50	2.2 Number of words recalled Standard Error 0.50

PRIMARY outcome

Timeframe: 6 months

In the logical delayed memory test, participants are read a logically organized story. Approximately 20 minutes later, the participants are asked to recall the story from memory (Delayed Recall). The version used in this study uses only one story (Story A) read once to participants at each study visit. Possible scores for delayed recall trials range from 0 to 25, with higher scores reflecting more details recalled.

Outcome measures

Measure	Placebo n=29 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=28 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Immediate and Delayed Recall on Verbal Memory/ Logical Memory Immediate and Delayed Recall: Number of Story Elements Recalled	4.6 Number of story elements recalled Standard Error 0.95	5.7 Number of story elements recalled Standard Error 0.9

PRIMARY outcome

Timeframe: 6 months

Trail Making Test-Version B (TMT B) [113], a measure of divided attention, the subject is asked to draw lines to connect consecutively numbered and lettered circles, alternating between the 2 sequences. The time needed to complete the task is recorded.

More time taken to complete the test or higher score indicates lower executive function/higher impairment.

Outcome measures

Measure	Placebo n=25 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=27 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Measure of Divided Attention: Time to Complete Trail Making Test B	95.5 Seconds Standard Error 16.7	95.7 Seconds Standard Error 16.0

PRIMARY outcome

Timeframe: 6 months

Time to complete mazes is a test of planning. Subjects are asked to complete a set of 3 mazes. The time taken to complete the maze is inversely proportional to the cognitive function.

Outcome measures

Measure	Placebo n=27 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=26 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
A Test of Planning: Time to Complete Mazes	32.2 Seconds Standard Error 5.3	22.6 Seconds Standard Error 5.4

PRIMARY outcome

Timeframe: 6 months

Selective attention was evaluated with the Stroop Color Word Interference Test. In the interference portion of this test, the subject identifies the color of ink in which words ("red", "green", or "blue") are printed, requiring the subject to inhibit their natural tendency to read the word. A subject's score is the time taken to identify 50 stimulus items.

The time taken to complete the maze is inversely proportional to the cognitive function.

Outcome measures

Measure	Placebo n=27 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=27 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Measure of Selective Attention: Time to Complete Stroop Color Word Test	105 Seconds Standard Error 12	91.8 Seconds Standard Error 12

PRIMARY outcome

Timeframe: 6 months

Visual memory will be evaluated by complex figure delayed recall test. In this test , a two dimensional figure is shown to the subjects. After a delay of 30 min, they are asked to draw the same figure based on their memory. The Complex Figure Test assesses the subject's ability to remember a 2-dimensional figure presented briefly. The scoring system used includes scores related to location, accuracy and organization. Higher score correlates to better visual memory.

Outcome measures

Measure	Placebo n=28 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=29 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Visual Memory Test: Complex Figure Delayed Recall; Number of Points	10.6 number of points Standard Error 1.8	13.4 number of points Standard Error 1.8

PRIMARY outcome

Timeframe: 6 months

The Benton Visual Retention Test (or simply Benton test or BVRT) is an individually administered test for people aged from 8 years to adulthood that measures visual perception and visual memory. It can also be used to help identify possible learning disabilities among other afflictions that might affect an individual's memory. The individual examined is shown 10 designs, one at a time, and asked to reproduce each one as exactly as possible on plain paper from memory. The test is untimed, and the results are professionally scored by form, shape, pattern, and arrangement on the paper.

For the 'test of number of correct figures' score is calculated based on an all-or-nothing approach; points are awarded if the reproduction of the design matches the original.

Outcome measures

Measure	Placebo n=28 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=28 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Visual Memory : Benton Visual Retention Test: Number of Correct Figures	2.7 number of correct figures Standard Error 0.4	2.8 number of correct figures Standard Error 0.4

PRIMARY outcome

Timeframe: 6 months

The Benton Visual Retention Test is an individually administered test for people aged from 8 years to adulthood that measures visual perception and visual memory. It can also be used to help identify possible learning disabilities among other afflictions that might affect an individual's memory. The individual examined is shown 10 designs, one at a time, and asked to reproduce each one as exactly as possible on plain paper from memory. The test is untimed, and the results are professionally scored by form, shape, pattern, and arrangement on the paper.

For the 'test of number of errors' score is calculated based on the number and type of errors made for each design. The major categories for these errors are omissions, distortions, perseverations, rotations, misplacements, and size errors.These scores are then be compared to several sets of normative data available in the manual, each representing different demographic characteristics, and conclusions can be drawn by the examiner.

Outcome measures

Measure	Placebo n=28 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=28 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Cognitive Outcomes - Visual Memory : Benton Visual Retention; Number of Errors	14.5 Number of errors Standard Error 1.2	13.1 Number of errors Standard Error 1.2

SECONDARY outcome

Timeframe: 6 months

Visual memory will be evaluated by Complex Figure copy test. The Complex Figure Test assesses the subject's ability to copy a 2-dimensional figure. The scoring system used include scores related to location, accuracy and organization. Higher score correlates to better visual memory.

Outcome measures

Measure	Placebo n=28 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=29 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Cognitive Outcomes - Visual Motor : Complex Figure Copy; Number of Points	27.6 number of points Standard Error 1.1	29.0 number of points Standard Error 1.1

SECONDARY outcome

Timeframe: 6 months

The Grooved Pegboard is a dexterity test consisting of 25 holes with randomly positioned slots. Pegs with a key on one side must be rotated to match the hole before they can be inserted. Participants are instructed to place all pegs into the 25 holes, picking up one at a time, and using just one hand. They use their dominant hand. Time taken to finish the test inversely correlates to the cognitive ability.

Outcome measures

Measure	Placebo n=24 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=27 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Cognitive Outcomes - Visual Motor : Time to Complete Grooved Pegboard Test Using the Dominant Hand	134.3 time in seconds Standard Error 17.6	149.8 time in seconds Standard Error 16.6

SECONDARY outcome

Timeframe: 6 months

The Grooved Pegboard is a dexterity test consisting of 25 holes with randomly positioned slots. Pegs with a key on one side must be rotated to match the hole before they can be inserted. Participants are instructed to place all pegs into the 25 holes, picking up one at a time, and using just one hand. They use their non-dominant hand. Time taken to finish the test inversely correlates to the cognitive ability.

Outcome measures

Measure	Placebo n=22 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=26 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Cognitive Outcomes - Visual Motor : Time to Complete Grooved Pegboard Test Using the Non-Dominant Hand	161.8 time in seconds Standard Error 24.4	156 time in seconds Standard Error 22.4

SECONDARY outcome

Timeframe: 6 months

During the MMSE, a health professional asks a participant a series of questions designed to test memory, ability to solve simple problems and other thinking skills.

The maximum MMSE score - 30 points. Score of 20 to 24 - mild dementia, 13 to 20 - moderate dementia, and <12 indicates severe dementia.

On average, the MMSE score of a person with Alzheimer's declines about 2 to 4 points each year.

Outcome measures

Measure	Placebo n=29 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=30 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Cognitive Outcomes-Global Cognition : Mini-Mental State Examination (MMSE) Score	21.3 score on a scale Standard Deviation 1.0	23.4 score on a scale Standard Deviation 1.0

SECONDARY outcome

Timeframe: 6 months

Depression scale is one of the subscale of POMS. Depression scale has 15 items and scores ranges from 0-60. Higher score indicates more severe depression.

Outcome measures

Measure	Placebo n=28 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=28 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Multiple Mood States: Profile of Mood States (POMS)-Depression Scale	9 score on a scale Standard Error 1.8	11.4 score on a scale Standard Error 1.7

SECONDARY outcome

Timeframe: 6 months

Tension scale is one of the subscale of POMS. Tension scale has 9 items and scores ranges from 0-36. Higher score indicates more severe outcomes.

Outcome measures

Measure	Placebo n=28 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=28 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Multiple Mood States: Profile of Mood States (POMS)-Tension Scale	8.2 score on a scale Standard Error 1.3	9.3 score on a scale Standard Error 1.3

SECONDARY outcome

Timeframe: 6 months

Anger scale is one of the subscale of POMS. Tension scale has 12 items and scores ranges from 0-48. Higher score indicates more anger issues.

Outcome measures

Measure	Placebo n=28 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=28 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Multiple Mood States: Profile of Mood States (POMS)-Anger Scale	6.8 score on a scale Standard Error 1.4	8.3 score on a scale Standard Error 1.4

SECONDARY outcome

Timeframe: 6 months

Fatigue scale is one of the subscale of POMS. Tension scale has 7 items and scores ranges from 0-28. Higher score indicates more fatigue.

Outcome measures

Measure	Placebo n=28 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=28 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Multiple Mood States: Profile of Mood States (POMS)-Fatigue Scale	10.3 score on a scale Standard Error 1.2	10.3 score on a scale Standard Error 1.2

SECONDARY outcome

Timeframe: 6 months

Vigor scale is one of the subscale of POMS. Vigor scale has 8 items and scores ranges from 0-32. Higher score indicates more severe outcomes.

Outcome measures

Measure	Placebo n=28 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=28 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Multiple Mood States: Profile of Mood States (POMS)-Vigor Scale	12.4 score on a scale Standard Error 1.1	12.0 score on a scale Standard Error 1.1

SECONDARY outcome

Timeframe: 6 months

Confusion scale is one of the subscale of POMS. Confusion scale has 7 items and scores ranges from 0-28. Higher score indicates more severe outcomes.

Outcome measures

Measure	Placebo n=28 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=28 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Multiple Mood States: Profile of Mood States (POMS)-Confusion Scale	15.5 score on a scale Standard Error 1.1	14 score on a scale Standard Error 1.1

SECONDARY outcome

Timeframe: 6 months

Geriatric Depression Scale (GDS) has been tested and used extensively with the older population to measure depression.

Subject will self-report a short form GDS consisting of 15 questions. Out of 15 items, 10 indicate the presence of depression when answered positively, while the rest (question numbers 1, 5, 7, 11, 13) indicate depression when answered negatively.

Scores of 0-4 are considered normal, depending on age, education, and complaints; Scores of 5-8 indicate mild depression; 9-11 indicate moderate depression; and Scores of 12-15 indicate severe depression.

The Short Form is more easily used by physically ill and mildly to moderately demented patients who have short attention spans and/or feel easily fatigued. It takes about 5 to 7 minutes to complete

Outcome measures

Measure	Placebo n=29 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=28 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Geriatric Depression Scale-Subject Report	2.1 score on a scale Standard Error 0.6	3.3 score on a scale Standard Error 0.6

SECONDARY outcome

Timeframe: 6 months

Study partner is someone who has frequent contact with the subject (e.g. an average of 10 hours per week or more), and can accompany the subject to all clinic visits for the duration of the protocol.

Study partner will report a short form GDS consisting of 15 questions. Out of 15 items, 10 indicate the presence of depression when answered positively, while the rest (question numbers 1, 5, 7, 11, 13) indicate depression when answered negatively.

Scores of 0-4 are considered normal, depending on age, education, and complaints; Scores of 5-8 indicate mild depression; 9-11 indicate moderate depression; and Scores of 12-15 indicate severe depression.

The Short Form is more easily used by physically ill and mildly to moderately demented patients who have short attention spans and/or feel easily fatigued. It takes about 5 to 7 minutes to complete.

Outcome measures

Measure	Placebo n=29 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=28 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Geriatric Depression Scale-Study Partner Report	5.2 score on a scale Standard Error 0.7	6.3 score on a scale Standard Error 0.7

SECONDARY outcome

Timeframe: Baseline

Population: Older adults with Alzheimer's disease

The epsilon-4 allele of the apolipoprotein E gene (APOE4) has been consistently associated with a greater risk of Alzheimer's disease (AD) as well as an earlier onset of AD.

Determination of apolipoprotein E (APOE) genotype was performed on a non-fasting blood sample collected at Baseline, using standard Polymerase chain reaction (PCR) and DNA sequencing techniques in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory. DNA extracted from whole blood was amplified by PCR using specific primers for the ApoE gene and the DNA then sequenced and analyzed for genotype using the FinchTV program (Version 1.3; Geospiza, Inc.)

Outcome measures

Measure	Placebo n=33 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=32 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Number of Participants With ApoE4 Allele	15 Participants	16 Participants

SECONDARY outcome

Timeframe: baseline

Population: Data is unavailable for 2 subject from placebo group and 1 subjects from Novasoy group

Isoflavone assays will be performed on non-fasting blood samples collected at baseline.

Novasoy capsules predominantly contain purified glycoside forms of isoflavones known genistein and diadzein. The plasma level of genistein and diadzine will be measured in the participants plasma.There is large inter-individual variations in the extent of intestinal metabolism, even when the quantity of isoflavone intake is standardized. Equol is a metabolite of isoflavones. Equol has high biological efficacy. Therefore, along with genistein and diadzein, plasma levels of equol will be measured to understand the isoflavone metabolism in the participants.

Outcome measures

Measure	Placebo n=33 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=32 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Plasma Concentrations of Isoflavones at Baseline Daidzein	2.8 ng/ml Standard Deviation 6.1	1.3 ng/ml Standard Deviation 2.5
Plasma Concentrations of Isoflavones at Baseline Equol	0.3 ng/ml Standard Deviation 1.5	0.1 ng/ml Standard Deviation 0.5
Plasma Concentrations of Isoflavones at Baseline Genistein	4.8 ng/ml Standard Deviation 11.4	1.5 ng/ml Standard Deviation 2.6

SECONDARY outcome

Timeframe: At month 3

Population: Data is unavailable for 1 subject from each group

Isoflavone assays will be performed on non-fasting blood samples collected at month 3.

Novasoy capsules predominantly contain purified glycoside forms of isoflavones known genistein and diadzein. The plasma level of genistein and diadzine will be measured in the participants plasma.There is large inter-individual variations in the extent of intestinal metabolism, even when the quantity of isoflavone intake is standardized. Equol is a metabolite of isoflavones. Equol has high biological efficacy. Therefore, along with genistein and diadzein, plasma levels of equol will be measured to understand the isoflavone metabolism in the participants.

Outcome measures

Measure	Placebo n=33 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=32 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Plasma Concentrations of Isoflavones at Month 3 Daidzein	1.1 ng/ml Standard Deviation 2.3	197.3 ng/ml Standard Deviation 150.5
Plasma Concentrations of Isoflavones at Month 3 Equol	0.2 ng/ml Standard Deviation 0.5	20.3 ng/ml Standard Deviation 50.7
Plasma Concentrations of Isoflavones at Month 3 Genistein	2.1 ng/ml Standard Deviation 3.7	2777.7 ng/ml Standard Deviation 188.4

SECONDARY outcome

Timeframe: At month 6

Population: Data is unavailable for 1 subject from placebo group and 3 subjects from Novasoy group

Isoflavone assays will be performed on non-fasting blood samples collected at month 6.

Novasoy capsules predominantly contain purified glycoside forms of isoflavones known genistein and diadzein. The plasma level of genistein and diadzine will be measured in the participants plasma.There is large inter-individual variations in the extent of intestinal metabolism, even when the quantity of isoflavone intake is standardized. Equol is a metabolite of isoflavones. Equol has high biological efficacy. Therefore, along with genistein and diadzein, plasma levels of equol will be measured to understand the isoflavone metabolism in the participants.

Outcome measures

Measure	Placebo n=33 Participants 100mg/day matching placebo Placebo: 100mg/day matching placebo	Novasoy n=32 Participants 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones
Plasma Concentrations of Isoflavones at Month 6 Daidzein	10.6 ng/ml Standard Deviation 37.8	206.6 ng/ml Standard Deviation 156.8
Plasma Concentrations of Isoflavones at Month 6 Genistein	15.6 ng/ml Standard Deviation 35.4	338.6 ng/ml Standard Deviation 308.8
Plasma Concentrations of Isoflavones at Month 6 Equol	0.1 ng/ml Standard Deviation 0.6	19.6 ng/ml Standard Deviation 40.5

SECONDARY outcome

Timeframe: baseline

Population: Estradiol analysis done by the same investigator as part of another project with different subjects (PMID: 9054783 linked in the citation), did not show any change in the estradiol levels. Based on that, investigators did not see the justification for running these analyses in the current study. No estradiol analyses were performed for this study.

Estradiol assay will be performed on non-fasting blood samples collected at baseline using an enzyme immunoassay kit.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 3 month

Population: Estradiol analysis done by the same investigator as part of another project with different subjects (PMID: 9054783 linked in the citation), did not show any change in the estradiol levels. Based on that, investigators did not see the justification for running these analyses in the current study. No estradiol analyses were performed for this study.

Estradiol assay will be performed on non-fasting blood samples collected at baseline using an enzyme immunoassay kit.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: At 6 month

Population: Estradiol analysis done by the same investigator as part of another project with different subjects (PMID: 9054783 linked in the citation), did not show any change in the estradiol levels. Based on that, investigators did not see the justification for running these analyses in the current study. No estradiol analyses were performed for this study.

Estradiol assay will be performed on non-fasting blood samples collected at baseline using an enzyme immunoassay kit.

Outcome measures

Outcome data not reported

Adverse Events

Active

Serious events: 1 serious events

Other events: 25 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 23 other events

Deaths: 0 deaths

Serious adverse events

Measure	Active n=32 participants at risk 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones	Placebo n=33 participants at risk 100mg/day matching placebo Placebo: 100mg/day matching placebo
Nervous system disorders Death	0.00% 0/32	6.1% 2/33 • Number of events 2
Nervous system disorders Seizures	3.1% 1/32 • Number of events 1	0.00% 0/33
Blood and lymphatic system disorders DVT	0.00% 0/32	3.0% 1/33 • Number of events 1

Other adverse events

Measure	Active n=32 participants at risk 100mg/day soy isoflavones Novasoy: 100mg/day soy isoflavones	Placebo n=33 participants at risk 100mg/day matching placebo Placebo: 100mg/day matching placebo
General disorders other illness not related to treatment	78.1% 25/32 • Number of events 25	69.7% 23/33 • Number of events 23

Additional Information

Dr. Carey Gleason

University of Wisconsin

Phone: 608-280-7000

Email: ceg@medicine.wisc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place