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

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

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: S-equol and Placebo; Drug: Placebo and S-equol

Detailed Description

Enrolled participants with a diagnosis of Alzheimer's Disease (AD) will be randomized to receive either S-equol or placebo first, and then cross over to receive the opposite intervention. The study, therefore, consists of two treatment periods with randomly assigned treatment order. Specifically, subjects are randomized to either: (1) S-equol for one month, then placebo for one month; or (2) placebo for one month, then S-equol for one month.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Kansas
    • Fairway, Kansas, United States, 66205
      • Clinical and Translational Science Unit
    • Kansas City, Kansas, United States, 66160
      • University of Kansas Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: S-equol First, Then Placebo; In this arm, participants receive S-equol 50mg twice daily for one month, followed by placebo twice daily for one month. There was no washout period.	Drug: S-equol and Placebo; S-equol is an estrogen receptor β (ERβ) agonist. Provided in capsules. The placebo is a matched pill that cannot be distinguished from the active S-equol.; Other Names: S-equol is also called AUS-131
Other: Placebo First, Then S-equol; In this arm, participants receive placebo twice daily for one month, followed by S-equol 50mg twice daily for one month. There was no washout period.	Drug: Placebo and S-equol; S-equol is an estrogen receptor β (ERβ) agonist. Provided in capsules. The placebo is a matched pill that cannot be distinguished from the active S-equol.; Other Names: S-equol is also called AUS-131

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cytochrome Oxidase/Citrate Synthase (COX/CS) Activity	Cytochrome oxidase (COX) was measured in platelet mitochondria as a pseudo-first order rate constant (sec-1/mg protein), which was determined as a Vmax, spectrophotometrically, by tracking the change in absorbance as reduced cytochrome c is oxidized to oxidized cytochrome C. Citrate synthase (CS) is a soluble mitochondrial matrix enzyme whose activity was determined spectrophotometrically as a Vmax (micromoles/mg protein). Reporting the COX activity as a ratio to CS activity takes mitochondrial mass into account, and normalizes the COX activity per the amount of mitochondria present in the assay sample, with units 1/(seconds multiplied by micromoles).	Column 1 is the value after completing S-equol minus the value after completing placebo. For S-equol then placebo, this is the Visit 3 minus the Visit 4 COX/CS value. For placebo then S-equol, this is the Visit 4 minus the Visit 3 COX/CS value.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pattern of COX Activity Changes While on the Active Treatment Versus Placebo Arms of This Crossover Study.	Participants are defined as responders or non-responders depending on the slope of COX/CS activity change. Those in the "Responder" group have a greater slope of COX/CS activity change going from off- to on-S-equol as compared to going from on- to off-S-equol.	Visits 2, 3, 4
Montreal Cognitive Assessment (MoCA)	Scale range: 0-30. A higher score indicates better global cognitive performance.	Score after completion of S-equol minus score after completion of placebo. For S-equol then placebo, this is the Visit 3 minus the Visit 4 MoCA score. For placebo then S-equol, this is the Visit 4 minus the Visit 3 MoCA score.
Alzheimer's Disease Assessment Scale-Cognitive Portion (ADASCog-11)	Scale range: 0-70. A lower score indicates better global cognitive performance.	Score after completion of S-equol minus score after completion of placebo. For S-equol then placebo, this is the Visit 3 minus the Visit 4 ADASCog score. For placebo then S-equol, this is the Visit 4 minus the Visit 3 ADASCog score.
Logical Memory Test 1 (LMT1) - Immediate Recall	Scale range: 0-25. A higher score indicates better memory function.	Score after completion of S-equol minus score after completion of placebo. For S-equol then placebo, this is the Visit 3 minus the Visit 4 LMT1 score. For placebo then S-equol, this is the Visit 4 minus the Visit 3 LMT1 score.
Logical Memory Test 2 (LMT2) - Delayed Recall	Scale range: 0-25. A higher score indicates better memory performance.	Score after completion of S-equol minus score after completion of placebo. For S-equol then placebo, this is the Visit 3 minus the Visit 4 LMT2 score. For placebo then S-equol, this is the Visit 4 minus the Visit 3 LMT2 score.
Stroop Color Test Score	Scale range: 0-unlimited. A higher score indicates better executive function.	Score after completion of S-equol minus score after completion of placebo. For S-equol then placebo, this is the Visit 3 minus the Visit 4 Stroop Color Test score. For placebo then S-equol, this is the Visit 4 minus the Visit 3 Stroop Color Test score.
Stroop Word Test	Scale range: 0-unlimited. A higher score indicates better executive function.	Score after completion of S-equol minus score after completion of placebo. For S-equol then placebo, this is the Visit 3 minus the Visit 4 Stroop Word Test score. For placebo then S-equol, this is the Visit 4 minus the Visit 3 Stroop Word Test score.
Stroop Interference Test	Scale range: 0-unlimited. A higher score indicates better executive function.	Score after completing S-equol minus score after completing placebo. For S-equol then placebo, this is the Visit 3 minus the Visit 4 Stroop Interference score. For placebo then S-equol, this is the Visit 4 minus the Visit 3 Stroop Interference score.
Number of Participants With Adverse Events	List of adverse events as reported over the course of the study (safety labs, physical and neurological exams, vital signs, signs and symptoms).	4 Months: From Visit 1 (Day 0) through Visit 1 (end of month 1, +/- 7 days), Visit 2 (end of month 2, +/- 7 days), Visit 3 (end of month 3, +/- 7days), and Post-Interventions Phone Call (end of month 4, +/- 7 days)

Collaborators and Investigators

• Sponsor: Russell Swerdlow
• Collaborators: Ausio Pharmaceuticals, LLC
• Investigators: Principal Investigator: Russell Swerdlow, MD, University of Kansas Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): May 5, 2017
• Primary Completion (Actual): March 1, 2021
• Study Completion (Actual): March 1, 2021

Study Registration Dates

• First Submitted: March 29, 2017
• First Submitted That Met QC Criteria: March 29, 2017
• First Posted (Actual): April 4, 2017

Study Record Updates

• Last Update Posted (Actual): July 25, 2024
• Last Update Submitted That Met QC Criteria: July 16, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Estrogens, Non-Steroidal; Estrogens; Phytoestrogens; Equol
• Other Study ID Numbers: SEAD2 (Other Grant/Funding Number: Ausio (Solely funded by Ausio; was not an NIH-funded study))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No