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| ID | Type | Description | Link |
|---|---|---|---|
| SEAD2 | Other Grant/Funding Number | Ausio (Solely funded by Ausio; was not an NIH-funded study) |
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| Name | Class |
|---|---|
| Ausio Pharmaceuticals, LLC | INDUSTRY |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 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. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| S-equol and Placebo | Drug | 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. |
| 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. |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Russell Swerdlow, MD | University of Kansas Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical and Translational Science Unit | Fairway | Kansas | 66205 | United States | ||
| University of Kansas Medical Center |
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| ID | Title | Description |
|---|---|---|
| FG000 | S-equol First, Then Placebo | This was a cross-over study. Each participant acted as their own control. The order of the interventions was randomized. Each participant spent one month in each intervention arm. In this group, participants initially received S-equol for one month, and at the conclusion of that arm they were switched to the placebo for one month. There was no washout period. The S-equol was provided as 50 mg capsules, which were taken twice daily. |
| FG001 | Placebo First, Then S-equol | This was a cross-over study. Each participant acted as their own control. The order of the interventions was randomized. Each participant spent one month in each intervention arm. In this group, participants initially received placebo for one month, and at the conclusion of that arm they were switched to S-equol for one month. There was no washout period. The S-equol was provided as 50 mg capsules, which were taken twice daily. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | S-equol First, Then Placebo | This group received S-equol for one month, and then crossed over to receive placebo for one month. There was no washout period. |
| BG001 | Placebo First, Then S-Equol |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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). | Due to the pandemic, 1 participant in the Placebo, Then S-equol group did not complete the analysis. This subject was excluded from this primary analysis, and all secondary analyses except for the safety analysis. As the order of the intervention does not matter, all 39 participants who contributed COX/CS data to the final analysis are included. The mean (SD) value reflects the mean of values obtained when the COX/CS value while on placebo was subtracted from the COX/CS score while on S-equol. | Posted | Mean | Standard Deviation | 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. |
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)
Any untoward or unfavorable medical occurrence in a participant, including any abnormal sign (for example, abnormal physical exam or laboratory finding), symptom, or disease, temporally associated with the participant's participation in the research, whether or not considered related to the participant's participation in the research.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Prior to Starting Drug or Placebo | This includes all 40 participants, prior to the initiation of any treatment (S-equol or placebo). |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Dizziness | Ear and labyrinth disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Russell Swerdlow | University of Kansas Medical Center | 913-588-0970 | rswerdlow@kumc.edu |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Jun 9, 2020 | Jun 21, 2022 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D060754 | Equol |
| ID | Term |
|---|---|
| D007529 | Isoflavones |
| D005419 | Flavonoids |
| D002867 | Chromones |
| D001578 | Benzopyrans |
| D006574 |
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|
| Placebo and S-equol | Drug | 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. |
|
|
| 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) |
| Kansas City |
| Kansas |
| 66160 |
| United States |
This group received placebo for one month, then crossed over to receive S-equol for one month. There was no washout period.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
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| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
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|
|
| Secondary | 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. | Only the 20 participants who had baseline then S-equol then placebo values contributed to this analysis. | Posted | Number | participants | Visits 2, 3, 4 |
|
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|
| Secondary | Montreal Cognitive Assessment (MoCA) | Scale range: 0-30. A higher score indicates better global cognitive performance. | The one subject missing the COX/CS difference score was excluded from this analysis. The key measure is the difference score. Participants unable to contribute both S-equol and placebo scores were not included in the difference score analysis, but do contribute to the S-equol or placebo scores as available. | Posted | Mean | Standard Deviation | score on a scale | 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. |
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|
|
| Secondary | Alzheimer's Disease Assessment Scale-Cognitive Portion (ADASCog-11) | Scale range: 0-70. A lower score indicates better global cognitive performance. | The one subject missing the COX/CS difference score was excluded from this analysis. The key measure is the difference score. Participants unable to contribute both S-equol and placebo scores were not included in the difference score analysis, but do contribute to the S-equol or placebo scores as available. | Posted | Mean | Standard Deviation | score on a scale | 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. |
|
|
|
| Secondary | Logical Memory Test 1 (LMT1) - Immediate Recall | Scale range: 0-25. A higher score indicates better memory function. | The one subject missing the COX/CS difference score was excluded from this analysis. The key measure is the difference score. Participants unable to contribute both S-equol and placebo scores were not included in the difference score analysis, but do contribute to the S-equol or placebo scores as available. | Posted | Mean | Standard Deviation | score on a scale | 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. |
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|
| Secondary | Logical Memory Test 2 (LMT2) - Delayed Recall | Scale range: 0-25. A higher score indicates better memory performance. | The one subject missing the COX/CS difference score was excluded from this analysis. The key measure is the difference score. Participants unable to contribute both S-equol and placebo scores were not included in the difference score analysis, but do contribute to the S-equol or placebo scores as available. | Posted | Mean | Standard Deviation | score on a scale | 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. |
|
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| Secondary | Stroop Color Test Score | Scale range: 0-unlimited. A higher score indicates better executive function. | The one subject missing the COX/CS difference score was excluded from this analysis. The key measure is the difference score. Participants unable to contribute both S-equol and placebo scores were not included in the difference score analysis, but do contribute to the S-equol or placebo scores as available. | Posted | Mean | Standard Deviation | score on a scale | 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. |
|
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| Secondary | Stroop Word Test | Scale range: 0-unlimited. A higher score indicates better executive function. | The one subject missing the COX/CS difference score was excluded from this analysis. The key measure is the difference score. Participants unable to contribute both S-equol and placebo scores were not included in the difference score analysis, but do contribute to the S-equol or placebo scores as available. | Posted | Mean | Standard Deviation | score on a scale | 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. |
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| Secondary | Stroop Interference Test | Scale range: 0-unlimited. A higher score indicates better executive function. | The one subject missing the COX/CS difference score was excluded from this analysis. The key measure is the difference score. Participants unable to contribute both S-equol and placebo scores were not included in the difference score analysis, but do contribute to the S-equol or placebo scores as available. | Posted | Mean | Standard Deviation | score on a scale | 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. |
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| Secondary | 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). | All 40 enrolled participants contributed to the safety data | Posted | Number | participants | 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) |
|
|
|
| 0 |
| 40 |
| 0 |
| 40 |
| 1 |
| 40 |
| EG001 | While on S-equol | This includes all 40 participants while receiving S-equol 50mg twice daily for one month. | 0 | 40 | 0 | 40 | 8 | 40 |
| EG002 | While on Placebo | This includes all 40 participants while receiving placebo twice daily for one month. | 0 | 40 | 0 | 40 | 8 | 40 |
| EG003 | After Completing Both Drug and Placebo | This includes all 40 participants following completion of their courses of both S-equol and placebo, regardless of treatment order. | 0 | 40 | 0 | 40 | 4 | 40 |
| Food Allergy | Immune system disorders | Non-systematic Assessment |
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| Gastroesophageal Acid Reflux | Gastrointestinal disorders | Non-systematic Assessment |
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| Diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
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| Fecal Impaction | Gastrointestinal disorders | Non-systematic Assessment |
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| Bradycardia | Cardiac disorders | Non-systematic Assessment |
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| Blood Pressure Change | Cardiac disorders | Non-systematic Assessment |
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| Vasovagal Event | Surgical and medical procedures | Non-systematic Assessment |
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| Bruise | Injury, poisoning and procedural complications | Non-systematic Assessment |
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| Muscle Strain | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Osteoporosis | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
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| Tooth Extraction | Surgical and medical procedures | Non-systematic Assessment |
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| Retina Procedure | Surgical and medical procedures | Non-systematic Assessment |
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| Increased Urinary Frequency | Renal and urinary disorders | Non-systematic Assessment |
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| Kidney Stone | Renal and urinary disorders | Non-systematic Assessment |
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| Cough | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
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| Urinary Tract Infection | Infections and infestations | Non-systematic Assessment |
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| Viral Respiratory Infection/Cold | Infections and infestations | Non-systematic Assessment |
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| Tooth Abscess | Infections and infestations | Non-systematic Assessment |
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| Gum Infection | Infections and infestations | Non-systematic Assessment |
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| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |