S-Equol in Alzheimer's Disease 2 Trial

Study Overview
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Brief Summary
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By doing this study researchers hope to learn if S-equol, a compound that acts like estrogen in the body, causes an increase in mitochondrial activity. Researchers also hope to determine the safety and tolerability of a therapeutic dose of S-equol and whether or not it influences cognition.

Official Title
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S-Equol in Alzheimer's Disease 2 (SEAD2) Trial

Conditions
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Alzheimer Disease

Intervention / Treatment
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* Drug: S-equol
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Have a diagnosis of Alzheimer's Disease (AD) Have a study partner who has a close relationship with the participant and will attend study visits with the participant Do not possess an Alkylphenol ethoxylates 4 (APOE4) variant of the APOE gene Speak English as their primary language Have not had any medication changes within the past 30 days Exclusion Criteria: Reside in a nursing home or dementia special care unit Have a potentially confounding, serious medical risk such as insulin-requiring diabetes, any history of cancer that required a chemotherapy or radiation therapy intervention within the past 5 years, or a recent cardiac event Have any clinically significant abnormal safety laboratory values at the SEAD2 screening visit Have any clinically significant abnormal findings on vital signs measurements, or on physical or neurological examination at the SEAD2 screening visit Use any type of systemic estrogen or testosterone replacement therapy Has participated in another clinical trial or received any investigational drug or investigational therapy within 30 days before the screening visit

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: S-equol<br>Participants will receive S-equol 50mg twice daily for one month | Drug: S-equol<br>* S-equol is an estrogen receptor β (ERβ) agonist. Provided in capsules<br>* Other names: AUS-131;|
| Placebo Comparator: Placebo<br>Participants will receive matched placebo pill to take twice daily for one month | Other: Placebo<br>* Placebo capsules matched in size and color to S-equol capsules<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in cytochrome oxidase/citrate synthase (COX/CS) activity | Measured as the mean intra-individual COX/CS activity | One Month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety laboratories evaluation and participant/study partner reporting of symptoms or adverse events | Measured as adverse events reported over the course of the study (safety labs, physical and neurological exams, vital signs, signs and symptoms) | Month 4 | 
| Montreal Cognitive Assessment (MoCA) Determine if S-equol influences participant scores. | Scale range: 0-30 (higher score indicates better result) | Months 2, 3, 4 | 
| Alzheimer's Disease Assessment Scale-Cognitive Portion (ADASCog-11) Determine if S-equol influences participant scores. | Scale range: 0-70 (lower score indicates better result) | Months 2, 3, 4 | 
| Logical Memory Test (LMT) - immediate and delayed recall Determine if S-equol influences participant scores. | Scale range: 0-25 (higher score indicates better result) | Months 2, 3, 4 | 
| Stroop Test Determine if S-equol influences participant scores. | Scale range: 0-unlimited (higher score indicates better result) | Months 2, 3, 4 | 
| Pattern of COX activity changes while on the active treatment versus placebo arms of this crossover study. | Pts will categorically be defined as responders or non-responders depending on the slope of COS/CS activity change. | Months 1, 3, 4 |