Alzheimer DiseasePhase 1/2SEAD2NCT03101085
S-Equol in Alzheimer's Disease 2 Trial
A Phase 1/2 study of Alzheimer Disease, run by Russell Swerdlow at 2 sites in United States.
Trial 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 more about this study
- Who is it for?
- Ages 50 to 90 years
- Conditions the study is for
- Alzheimer Disease
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 40 participants
- Where
- 2 sitesUnited States
- Study dates
- 5 May 2017to 1 Mar 2021
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 50 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Clinical and Translational Science Unit
Fairway, Kansas, 66205
University of Kansas Medical Center
Kansas City, Kansas, 66160
About this study
Official title: 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.
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.
- Conditions
- Alzheimer Disease
- Being tested
- S-equol and Placebo, Placebo and S-equol
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
S-equol and PlaceboDrug
Also called S-equol is also called AUS-131
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.
Placebo and S-equolDrug
Also called S-equol is also called AUS-131
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.
| Study group | Role | What they receive |
|---|---|---|
| S-equol First, Then Placebo | Other | 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. Receives: Drug: S-equol and Placebo |
| Placebo First, Then S-equol | Other | 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. Receives: Drug: Placebo and S-equol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 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 (9)
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.
Measured: Visits 2, 3, 4
Montreal Cognitive Assessment (MoCA)
Scale range: 0-30. A higher score indicates better global cognitive performance.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Apr 2017
- Study start5 May 2017
- Primary completion1 Mar 2021
- Study completion1 Mar 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Alzheimer DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 40 participants (actual)
Sponsor and investigators
- Lead sponsor
- Russell Swerdlow
- Sponsor type
- University, hospital or other
- Collaborators
- Ausio Pharmaceuticals, LLC
- Responsible party
- Sponsor-investigator, Russell Swerdlow, University of Kansas Medical Center
- Investigators
- Russell Swerdlow, MD, Principal investigator, University of Kansas Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03101085
- Sponsor's protocol ID
- SEAD2
- Other IDs
- SEAD2
- Acronym
- SEAD2
- Status last verified
- Jul 2024
- First submitted
- 29 Mar 2017
- Last updated
- 25 Jul 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- S-Equol in Alzheimer's Disease 2 (SEAD2) Trial
- ClinicalTrials.gov ID
- NCT03101085
- Acronym / sponsor ID
- SEAD2 / SEAD2
- Conditions
- Alzheimer Disease
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 40 participants (actual)
- Lead sponsor
- Russell SwerdlowUniversity, hospital or other
- Collaborators
- Ausio Pharmaceuticals, LLC
- Study start
- 5 May 2017 (actual)
- Primary completion
- 1 Mar 2021 (actual)
- Study completion
- 1 Mar 2021 (actual)
- First posted
- 4 Apr 2017 (actual)
- Results
- Posted 17 Jul 2024
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| S-equol First, Then Placebo | Other | Drug: S-equol and PlaceboIn 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. |
| Placebo First, Then S-equol | Other | Drug: Placebo and S-equolIn 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. |
Who may qualify
- Ages
- 50 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (6 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| S-equol and PlaceboAlso: S-equol is also called AUS-131S-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. | Drug | S-equol First, Then Placebo |
| Placebo and S-equolAlso: S-equol is also called AUS-131S-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. | Drug | Placebo First, Then S-equol |
Primary outcome
Cytochrome Oxidase/Citrate Synthase (COX/CS) Activity
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.
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).
9 secondary outcomes
Pattern of COX Activity Changes While on the Active Treatment Versus Placebo Arms of This Crossover Study.
Time frame: Visits 2, 3, 4
Montreal Cognitive Assessment (MoCA)
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.
Alzheimer's Disease Assessment Scale-Cognitive Portion (ADASCog-11)
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.
Logical Memory Test 1 (LMT1) - Immediate Recall
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.
Logical Memory Test 2 (LMT2) - Delayed Recall
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.
Stroop Color Test Score
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.
Stroop Word Test
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.
Stroop Interference Test
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.
Number of Participants With Adverse Events
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)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Russell Swerdlow, MD principal investigator
University of Kansas Medical Center
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study of Alzheimer Disease, run by Russell Swerdlow at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 25 Jul 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 17 Jul 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cytochrome Oxidase/Citrate Synthase (COX/CS) Activity (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.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2024.