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The purpose of this study is to determine if oxaloacetate (OAA) is safe and tolerable at doses of up to 2 grams per day in people with Alzheimer's disease (AD).
Alzheimer's disease (AD) is a progressive brain disorder that causes memory and thinking problems. The exact cause of AD is unknown. Researchers believe mitochondria (the part of your cells that produce energy) might be linked to symptoms of AD. Some studies have shown that the brains in patients with Alzheimer's disease have reduced mitochondrial activity, have fewer mitochondria present in the nerve cells, and have reduced ability to utilize glucose (sugar) for energy.
Oxaloacetate (OAA) is a natural chemical that has been shown to have an effect on brain mitochondrial activity and brain energy in non-human animals.
This study is divided into two parts. In the first part of the study, researchers will test whether a dose of 1 gram per day of OAA, taken for approximately 4 weeks in 15 people with AD is safe and tolerable. After all 15 participants in part 1 have completed their participation, and it is determined that the study drug was safe at this dose, the second part of the study will begin. In part 2, researchers will test a dose of 2 grams per day of OAA, taken for approximately 4 weeks in 15 people with AD, to assess safety at this dose.
Participants will be in this study for about 10 weeks.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Part 1 - Oxaloacetate (OAA) 1 gram/day | Experimental | Participants take 1 gram of OAA per day for period of 4 weeks |
|
| Part 2 - Oxaloacetate (OAA)2 gram/day | Experimental | Participants take 2 grams of OAA per day for period of 4 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Oxaloacetate (OAA) 1g | Drug | Pills to be taken orally in 500mg dose two times per day |
|
| Measure | Description | Time Frame |
|---|---|---|
| Number of Dose Limiting Toxicity Events | The number of dose limiting toxicity events will be determined by change in safety labs, physical and neurological exams, vital signs, cognitive measures, signs and symptoms. | Change from Baseline to Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Brain Glucose Metabolic Rate as Determined by Fluorodeoxyglucose Positron Emission Tomography (FDG PET) | Fluorodeoxyglucose positron emission tomography (FDG PET) | Change from Baseline to Week 4 |
| Change in Brain Lactate Levels as Determined by Magnetic Resonance Spectroscopy (MRS) |
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Inclusion Criteria:
Exclusion Criteria:
Dementia due to causes other than AD;
Potentially confounding, serious, or unstable medical conditions such as:
Any abnormal physical examination assessment or vital sign assessment at TOAD screening visit that is deemed to be clinically significant by the principal investigator;
Any abnormal clinical laboratory test result at TOAD screening visit that is deemed to be clinically significant by the principal investigator.
Any contraindication for undergoing magnetic resonance spectroscopy (MRS), such as the presence of metal implants, a cardiac pacemaker that is not compatible with MRS, or severe claustrophobia
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| Name | Affiliation | Role |
|---|---|---|
| Russell Swerdlow, MD | University of Kansas Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Kansas Medical Center | Kansas City | Kansas | 66160 | United States |
Original plan was to enroll 30 participants. After enrolling 30 participants, two enrolled participants were withdrawn from the study after assignment to groups but did not complete post treatment data collection. Therefore those two were replaced so that total number of participants who completed post treatment data was 30, increasing the total number of enrolled participants to 32.
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| ID | Title | Description |
|---|---|---|
| FG000 | Part 1 - Oxaloacetate (OAA) 1 Gram/Day | Participants take 1 gram of OAA per day for period of 4 weeks Oxaloacetate (OAA): Pills to be taken orally in 500mg or 1000mg doses two times per day depending on the part of the study |
| FG001 | Part 2 - Oxaloacetate (OAA)2 Gram/Day | Participants take 2 grams of OAA per day for period of 4 weeks Oxaloacetate (OAA): Pills to be taken orally in 500mg or 1000mg doses two times per day depending on the part of the study |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Part 1 - Oxaloacetate (OAA) 1 Gram/Day | Participants take 1 gram of OAA per day for period of 4 weeks Oxaloacetate (OAA): Pills to be taken orally in 500mg or 1000mg doses two times per day depending on the part of the study |
| BG001 | Part 2 - Oxaloacetate (OAA)2 Gram/Day |
| 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 | Number of Dose Limiting Toxicity Events | The number of dose limiting toxicity events will be determined by change in safety labs, physical and neurological exams, vital signs, cognitive measures, signs and symptoms. | Posted | Number | Dose Limiting Toxicity Events | Change from Baseline to Week 4 |
|
8 weeks
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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 | Part 1 - Oxaloacetate (OAA) 1 Gram/Day | Participants take 1 gram of OAA per day for period of 4 weeks Oxaloacetate (OAA): Pills to be taken orally in 500mg or 1000mg doses two times per day depending on the part of the study |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Increased confusion | Nervous system disorders | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Russell H. Swerdlow, MD | University of Kansas Medical Center | 9135885000 | rswerdlow@kumc.edu |
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Aug 31, 2017 | Jun 17, 2021 | Prot_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 |
|---|---|
| D062907 | Oxaloacetic Acid |
| ID | Term |
|---|---|
| D010071 | Oxaloacetates |
| D010070 | Oxalates |
| D003998 | Dicarboxylic Acids |
| D000144 | Acids, Acyclic |
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| Oxaloacetate (OAA) 2g | Drug | Pills to be taken orally in 1000mg dose two times per day. |
|
|
magnetic resonance spectroscopy (MRS) |
| Change from Baseline to Week 4 |
| Plasma Levels in 500 mg Bid Cohort at Baseline, 60 and 90 Minutes Post-Dose | For the 1 g/ day (500 mg bid) cohort, baseline blood sample will be obtained just before 500 mg OAA is administered. Blood samples to be drawn again at 60 min and 90 min post administration of dose. The amount of OOA in the blood will be measured at each of the three time points. | Change from dose to 60 min post dose and 90 min post dose |
| Plasma Levels in 1000 mg Bid Cohort at Baseline, 60 and 90 Minutes Post-Dose | For the 2 g/ day (1000 mg bid) cohort, baseline blood sample will be obtained before 1000 mg OAA is administered. Blood samples to be drawn again at 60 min and 90 min post administration of dose. Plasma levels of OOA will be measured at each of the three timepoints. | Change from dose to 60 min post dose and 90 min post dose |
Participants take 2 grams of OAA per day for period of 4 weeks Oxaloacetate (OAA): Pills to be taken orally in 500mg or 1000mg doses two times per day depending on the part of the study |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race and Ethnicity Not Collected | Race and Ethnicity were not collected from any participant. | Count of Participants | Participants |
|
| Region of Enrollment | Count of Participants | Participants |
|
| Baseline MMSE | The Mini-Mental State Exam (MMSE) is a 30 point questionnaire that measures cognitive impairment. Score ranges from 0 to 30 and are adjusted based on education level of the participant. A score of 20 to 24 suggests mild dementia, a score of 13 to 20 suggest moderate dementia, and a score of 12 or less suggests severe dementia. | Mean | Standard Deviation | Scores on a Scale |
|
|
|
| Secondary | Change in Brain Glucose Metabolic Rate as Determined by Fluorodeoxyglucose Positron Emission Tomography (FDG PET) | Fluorodeoxyglucose positron emission tomography (FDG PET) | Not Posted | Change from Baseline to Week 4 | Participants |
| Secondary | Change in Brain Lactate Levels as Determined by Magnetic Resonance Spectroscopy (MRS) | magnetic resonance spectroscopy (MRS) | Not Posted | Change from Baseline to Week 4 | Participants |
| Secondary | Plasma Levels in 500 mg Bid Cohort at Baseline, 60 and 90 Minutes Post-Dose | For the 1 g/ day (500 mg bid) cohort, baseline blood sample will be obtained just before 500 mg OAA is administered. Blood samples to be drawn again at 60 min and 90 min post administration of dose. The amount of OOA in the blood will be measured at each of the three time points. | Posted | Mean | Standard Deviation | ng/mL | Change from dose to 60 min post dose and 90 min post dose |
|
|
|
| Secondary | Plasma Levels in 1000 mg Bid Cohort at Baseline, 60 and 90 Minutes Post-Dose | For the 2 g/ day (1000 mg bid) cohort, baseline blood sample will be obtained before 1000 mg OAA is administered. Blood samples to be drawn again at 60 min and 90 min post administration of dose. Plasma levels of OOA will be measured at each of the three timepoints. | Posted | Mean | Standard Deviation | ng/mL | Change from dose to 60 min post dose and 90 min post dose |
|
|
|
| 0 |
| 15 |
| 0 |
| 15 |
| 4 |
| 15 |
| EG001 | Part 2 - Oxaloacetate (OAA)2 Gram/Day | Participants take 2 grams of OAA per day for period of 4 weeks Oxaloacetate (OAA): Pills to be taken orally in 500mg or 1000mg doses two times per day depending on the part of the study | 0 | 15 | 0 | 15 | 3 | 15 |
| Cervical Stenosis | Nervous system disorders | Non-systematic Assessment |
|
| Syncope | General disorders | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | Non-systematic Assessment |
|
| Sinus Infection | Infections and infestations | Non-systematic Assessment |
|
| Breast calcification | Reproductive system and breast disorders | Non-systematic Assessment |
|
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| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D002264 |
| Carboxylic Acids |
| D009930 | Organic Chemicals |
| D007651 | Keto Acids |