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CompletedNCT03101085SEAD2Updated Jul 25, 2024Results posted

S-Equol in Alzheimer's Disease 2 Trial

A Phase 1/2 interventional study of S-equol and Placebo and Placebo and S-equol in Alzheimer Disease, sponsored by Russell Swerdlow. Completed at 2 sites in United States. Open to participants aged 50 Years to 90 Years. Per ClinicalTrials.gov, last updated 2024-07-25.

Sponsored by Russell Swerdlow · Phase 1/2, Interventional, and Treatment

Phase
Phase 1/2
Study type
Interventional
Enrollment
40
Allocation
Randomized
Ages
50 Years to 90 Years
Sex
All
01

Study summary

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.

Read the 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.

02

Conditions studied

  • Alzheimer Disease

Browse trials for

03

In context

Alzheimer Disease

3,765 studies on the registry are indexed under Alzheimer Disease; 881 are open to participants now.

This study's enrollment of 40 is below the median of 68 across 2,861 interventional studies indexed under Alzheimer Disease.

Browse Alzheimer Disease studies →

Lead sponsor

Russell Swerdlow is the lead sponsor of 2 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
50 Years to 90 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
05

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Crossover assignment
Masking
Double (Participant, Investigator)
Enrollment
40 participants (actual)

Study arms

  • 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

  • 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

Interventions

  • DrugS-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.

    Also known as: S-equol is also called AUS-131

  • DrugPlacebo 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.

    Also known as: S-equol is also called AUS-131

06

What researchers measure

Primary outcomes

  1. 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).

    Time frame: 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 outcomes

  1. 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.

    Time frame: Visits 2, 3, 4

  2. Montreal Cognitive Assessment (MoCA)

    Scale range: 0-30. A higher score indicates better global cognitive performance.

    Time frame: 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.

  3. Alzheimer's Disease Assessment Scale-Cognitive Portion (ADASCog-11)

    Scale range: 0-70. A lower score indicates better global cognitive performance.

    Time frame: 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.

  4. Logical Memory Test 1 (LMT1) - Immediate Recall

    Scale range: 0-25. A higher score indicates better memory function.

    Time frame: 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.

  5. Logical Memory Test 2 (LMT2) - Delayed Recall

    Scale range: 0-25. A higher score indicates better memory performance.

    Time frame: 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.

  6. Stroop Color Test Score

    Scale range: 0-unlimited. A higher score indicates better executive function.

    Time frame: 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.

  7. Stroop Word Test

    Scale range: 0-unlimited. A higher score indicates better executive function.

    Time frame: 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.

  8. Stroop Interference Test

    Scale range: 0-unlimited. A higher score indicates better executive function.

    Time frame: 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.

  9. 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).

    Time frame: 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)

07

Results

Posted Jul 17, 2024

Participant flow

Participant flow — Overall Study
MilestoneS-equol First, Then PlaceboPlacebo First, Then S-equol
Started2020
Completed2019
Not completed01
Withdrew: Lost to follow-up01

Outcome measures

PrimaryCytochrome 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).

Time frame:
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.
Reported as:
Mean · 1/(seconds multiplied by micromoles)
Cytochrome Oxidase/Citrate Synthase (COX/CS) Activity
1/(seconds multiplied by micromoles)Difference (on S-equol Minus on Placebo)S-equolPlacebo
Cytochrome Oxidase/Citrate Synthase (COX/CS) Activity-0.0000049 ± 0.0000240.0000195 ± 0.00000810.0000245 ± 0.0000258
Statistical analysis
  • Difference (on S-equol Minus on Placebo) · Paired T-test · p = >0.05
SecondaryPattern 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.

Time frame:
Visits 2, 3, 4
Reported as:
Number · participants
Pattern of COX Activity Changes While on the Active Treatment Versus Placebo Arms of This Crossover Study.
participantsS-equol Then Placebo Subjects Only
Pattern of COX Activity Changes While on the Active Treatment Versus Placebo Arms of This Crossover Study.7
SecondaryMontreal Cognitive Assessment (MoCA)

Scale range: 0-30. A higher score indicates better global cognitive performance.

Time frame:
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.
Reported as:
Mean · score on a scale
Montreal Cognitive Assessment (MoCA)
score on a scaleDifference (on S-equol Minus on Placebo)S-equolPlacebo
Montreal Cognitive Assessment (MoCA)0.2 ± 2.412.3 ± 6.312.0 ± 6.1
SecondaryAlzheimer's Disease Assessment Scale-Cognitive Portion (ADASCog-11)

Scale range: 0-70. A lower score indicates better global cognitive performance.

Time frame:
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.
Reported as:
Mean · score on a scale
Alzheimer's Disease Assessment Scale-Cognitive Portion (ADASCog-11)
score on a scaleDifference (on S-equol Minus on Placebo)S-equolPlacebo
Alzheimer's Disease Assessment Scale-Cognitive Portion (ADASCog-11)1.1 ± 5.524.6 ± 11.323.5 ± 10.6
SecondaryLogical Memory Test 1 (LMT1) - Immediate Recall

Scale range: 0-25. A higher score indicates better memory function.

Time frame:
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.
Reported as:
Mean · score on a scale
Logical Memory Test 1 (LMT1) - Immediate Recall
score on a scaleDifference (on S-equol Minus on Placebo)S-equolPlacebo
Logical Memory Test 1 (LMT1) - Immediate Recall0.2 ± 2.94.1 ± 4.23.9 ± 3.3
SecondaryLogical Memory Test 2 (LMT2) - Delayed Recall

Scale range: 0-25. A higher score indicates better memory performance.

Time frame:
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.
Reported as:
Mean · score on a scale
Logical Memory Test 2 (LMT2) - Delayed Recall
score on a scaleDifference (on S-equol Minus on Placebo)S-equolPlacebo
Logical Memory Test 2 (LMT2) - Delayed Recall0.2 ± 2.01.9 ± 3.41.8 ± 2.7
SecondaryStroop Color Test Score

Scale range: 0-unlimited. A higher score indicates better executive function.

Time frame:
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.
Reported as:
Mean · score on a scale
Stroop Color Test Score
score on a scaleDifference (on S-equol Minus on Placebo)S-equolPlacebo
Stroop Color Test Score-0.1 ± 5.840.0 ± 20.939.3 ± 18.5
SecondaryStroop Word Test

Scale range: 0-unlimited. A higher score indicates better executive function.

Time frame:
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.
Reported as:
Mean · score on a scale
Stroop Word Test
score on a scaleDifference (on S-equol Minus on Placebo)S-equolPlacebo
Stroop Word Test-0.1 ± 9.556.1 ± 23.156.3 ± 21.9
SecondaryStroop Interference Test

Scale range: 0-unlimited. A higher score indicates better executive function.

Time frame:
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.
Reported as:
Mean · score on a scale
Stroop Interference Test
score on a scaleDifference (on S-equol Minus on Placebo)S-equolPlacebo
Stroop Interference Test-1.2 ± 6.814.5 ± 7.415.3 ± 8.2
SecondaryNumber 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).

Time frame:
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)
Reported as:
Number · participants
Number of Participants With Adverse Events
participantsPrior to Starting Drug or PlaceboWhile on S-equolWhile on PlaceboAfter Completing Both Drug and Placebo
Number of Participants With Adverse Events1884

Adverse events

Collected over 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). Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Prior to Starting Drug or Placebo0/40 (0%)0/40 (0%)1/40 (2.5%)
While on S-equol0/40 (0%)0/40 (0%)8/40 (20%)
While on Placebo0/40 (0%)0/40 (0%)8/40 (20%)
After Completing Both Drug and Placebo0/40 (0%)0/40 (0%)4/40 (10%)
Most frequent other events
Showing 10 of 20
Most frequent other events
EventPrior to Starting Drug or PlaceboWhile on S-equolWhile on PlaceboAfter Completing Both Drug and Placebo
DizzinessEar and labyrinth disorders0/400/400/401/40
Food AllergyImmune system disorders0/400/401/400/40
Gastroesophageal Acid RefluxGastrointestinal disorders—1/400/400/40
DiarrheaGastrointestinal disorders0/400/401/400/40
Fecal ImpactionGastrointestinal disorders0/400/401/400/40
BradycardiaCardiac disorders0/401/400/400/40
Blood Pressure ChangeCardiac disorders0/400/401/400/40
Vasovagal EventSurgical and medical procedures0/400/401/400/40
BruiseInjury, poisoning and procedural complications0/401/400/400/40
Muscle StrainMusculoskeletal and connective tissue disorders0/401/400/400/40

Baseline characteristics

Age, Continuous
Age, Continuous(years)S-equol First, Then PlaceboPlacebo First, Then S-EquolTotal
Mean76.7 ± 7.271.7 ± 8.474.2 ± 8.2
Sex: Female, Male
Sex: Female, Male(Participants)S-equol First, Then PlaceboPlacebo First, Then S-EquolTotal
Female91221
Male11819
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)S-equol First, Then PlaceboPlacebo First, Then S-EquolTotal
Hispanic or Latino000
Not Hispanic or Latino202040
Unknown or Not Reported000
Race (NIH/OMB)
Race (NIH/OMB)(Participants)S-equol First, Then PlaceboPlacebo First, Then S-EquolTotal
American Indian or Alaska Native000
Asian000
Native Hawaiian or Other Pacific Islander000
Black or African American202
White182038
More than one race000
Unknown or Not Reported000
08

Study locations

2 sites
  • Clinical and Translational Science Unit
    Fairway, Kansas 66205, United States
  • University of Kansas Medical Center
    Kansas City, Kansas 66160, United States
09

References and documents

Study documents

  • Protocol and statistical analysis plan · Jun 9, 2020

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

10

Timeline

Tracking since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reachedSimilar studies: half by the dot; the band is the middle halfHalf of similar studies reached it by the dot; the band is the middle half, from a quarter to three quarters

Ran from May 2017 to primary completion in Mar 2021, 45 months.

Results were first posted in Jul 2024, 3 years 4 months after primary completion.

Of 56 phase 1/2 interventional studies under Alzheimer Disease, half reached primary completion within 41 months of starting (the median), counting those still running; a quarter within 21 and three quarters within 63. This study's 45 months is close to that.

How these figures are worked out, and which studies are left out of them.

Registered
Mar 29, 2017
First posted
Apr 4, 2017
StartActual
May 5, 2017
Primary completionActual
Mar 1, 2021
CompletionActual
Mar 1, 2021
Results first posted
Jul 17, 2024
Last update
Jul 25, 2024
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jul 25, 2024, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT03101085
Lead sponsor
Russell Swerdlow
Collaborators
Ausio Pharmaceuticals, LLC
Responsible party
Russell Swerdlow (Professor, University of Kansas Medical Center) — Sponsor-investigator
First posted
Apr 4, 2017
Start date
May 5, 2017
Primary completion
Mar 1, 2021
Completion
Mar 1, 2021
Results posted
Jul 17, 2024
Last update
Jul 25, 2024

Study contacts

Russell Swerdlow, MD
principal investigator · University of Kansas Medical Center

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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