Alzheimer's Disease (AD)Phase 1TOADNCT02593318
Trial of Oxaloacetate in Alzheimer's Disease (TOAD)
A Phase 1 study testing Oxaloacetate (OAA) 1g and Oxaloacetate (OAA) 2g in people with Alzheimer's Disease (AD), run by Russell Swerdlow at 1 site in United States.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 50 to 85 years
- Conditions the study is for
- Alzheimer's Disease (AD)
- What is being tested?
- Oxaloacetate (OAA) 1g and Oxaloacetate (OAA) 2g
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2015to Sep 2018
- Phase
- Phase 1
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Have a diagnosis of probable Alzheimer's disease (AD) per McKhann et al. criteria [9];
- Have a clinical dementia rating (CDR) score of 0.5 or 1 at time of their last University of Kansas Alzheimer's Disease Center (KU ADC) assessment;
- Have a Mini Mental Status Exam (MMSE) score of 15-28 at the TOAD screening visit;
- Have a reliable and competent study partner who is willing to accompany the participant to all study visits, monitor compliance of study medication administration, and observe/report any changes in the participant's health throughout the study duration;
- Are on stable doses of concurrent medications for at least 4 weeks prior to the TOAD screening visit; and
- Speaks English as his/her primary language.
- If female of child-bearing potential, must have a negative urine pregnancy test at TOAD screening visit (and must agree to use of contraception throughout the trial)
Who cannot join
- Dementia due to causes other than AD;
- Potentially confounding, serious, or unstable medical conditions such as:
- insulin-dependent diabetes mellitus
- cancer within the past 3 years (except basal cell, squamous cell, or localized prostate cancer)
- a recent cardiac event (i.e. heart attack, angioplasty, etc. within the 6 months prior to screening visit)
- other conditions that pose a potential safety risk or confounding factor in the investigator's opinion;
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Kansas Medical Center
Kansas City, Kansas, 66160
About this study
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).
Read the detailed description
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.
- Conditions
- Alzheimer's Disease (AD)
- Being tested
- Oxaloacetate (OAA) 1g, Oxaloacetate (OAA) 2g
- Keywords
- energy metabolism, oxaloacetate
- Medical subject headings
- Alzheimer Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Oxaloacetate (OAA) 1gDrug
Also called Oxobutanedioic acid, Oxaloacetic acid, Oxalacetic acid, 2-Oxosuccinic acid
Pills to be taken orally in 500mg dose two times per day
Oxaloacetate (OAA) 2gDrug
Also called Oxobutanedioic acid, Oxaloacetic acid, Oxalacetic acid, 2-Oxosuccinic acid
Pills to be taken orally in 1000mg dose two times per day.
| Study group | Role | What they receive |
|---|---|---|
| Part 1 - Oxaloacetate (OAA) 1 gram/day | Experimental | Participants take 1 gram of OAA per day for period of 4 weeks Receives: Drug: Oxaloacetate (OAA) 1g |
| Part 2 - Oxaloacetate (OAA)2 gram/day | Experimental | Participants take 2 grams of OAA per day for period of 4 weeks Receives: Drug: Oxaloacetate (OAA) 2g |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Change from Baseline to Week 4
Secondary outcomes (4)
Change in Brain Glucose Metabolic Rate as Determined by Fluorodeoxyglucose Positron Emission Tomography (FDG PET)
Fluorodeoxyglucose positron emission tomography (FDG PET)
Measured: Change from Baseline to Week 4
Change in Brain Lactate Levels as Determined by Magnetic Resonance Spectroscopy (MRS)
magnetic resonance spectroscopy (MRS)
Measured: 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.
Measured: 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.
Measured: Change from dose to 60 min post dose and 90 min post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Nov 2015 (estimated)
- Study startOct 2015
- Primary completionSep 2018
- Study completionSep 2018
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's Disease (AD)Studies 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Russell Swerdlow
- Sponsor type
- University, hospital or other
- 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
- NCT02593318
- Sponsor's protocol ID
- STUDY00002242
- Acronym
- TOAD
- Status last verified
- Jun 2021
- First submitted
- 8 Oct 2015
- Last updated
- 9 Jul 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Trial of Oxaloacetate in Alzheimer's Disease (TOAD)
- ClinicalTrials.gov ID
- NCT02593318
- Acronym / sponsor ID
- TOAD / STUDY00002242
- Conditions
- Alzheimer's Disease (AD)
- Keywords
- energy metabolism, oxaloacetate
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Russell SwerdlowUniversity, hospital or other
- Study start
- Oct 2015
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 2 Nov 2015 (estimated)
- Results
- Posted 9 Jul 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Part 1 - Oxaloacetate (OAA) 1 gram/day | Experimental | Drug: Oxaloacetate (OAA) 1gParticipants take 1 gram of OAA per day for period of 4 weeks |
| Part 2 - Oxaloacetate (OAA)2 gram/day | Experimental | Drug: Oxaloacetate (OAA) 2gParticipants take 2 grams of OAA per day for period of 4 weeks |
Who may qualify
- Ages
- 50 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Have a diagnosis of probable Alzheimer's disease (AD) per McKhann et al. criteria [9];
- Have a clinical dementia rating (CDR) score of 0.5 or 1 at time of their last University of Kansas Alzheimer's Disease Center (KU ADC) assessment;
- Have a Mini Mental Status Exam (MMSE) score of 15-28 at the TOAD screening visit;
- Have a reliable and competent study partner who is willing to accompany the participant to all study visits, monitor compliance of study medication administration, and observe/report any changes in the participant's health throughout the study duration;
- Are on stable doses of concurrent medications for at least 4 weeks prior to the TOAD screening visit; and
Key exclusion criteria (9 listed)
- 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
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 |
|---|---|---|
| Oxaloacetate (OAA) 1gAlso: Oxobutanedioic acid, Oxaloacetic acid, Oxalacetic acid, 2-Oxosuccinic acidPills to be taken orally in 500mg dose two times per day | Drug | Part 1 - Oxaloacetate (OAA) 1 gram/day |
| Oxaloacetate (OAA) 2gAlso: Oxobutanedioic acid, Oxaloacetic acid, Oxalacetic acid, 2-Oxosuccinic acidPills to be taken orally in 1000mg dose two times per day. | Drug | Part 2 - Oxaloacetate (OAA)2 gram/day |
Primary outcome
Number of Dose Limiting Toxicity Events
Time frame: Change from Baseline to Week 4
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.
4 secondary outcomes
Change in Brain Glucose Metabolic Rate as Determined by Fluorodeoxyglucose Positron Emission Tomography (FDG PET)
Time frame: Change from Baseline to Week 4
Change in Brain Lactate Levels as Determined by Magnetic Resonance Spectroscopy (MRS)
Time frame: Change from Baseline to Week 4
Plasma Levels in 500 mg Bid Cohort at Baseline, 60 and 90 Minutes Post-Dose
Time frame: 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
Time frame: Change from dose to 60 min post dose and 90 min post dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Jul 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Oxaloacetate (OAA) 1g and Oxaloacetate (OAA) 2g in people with Alzheimer's Disease (AD), run by Russell Swerdlow at 1 site 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 7 inclusion and 9 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 9 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 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.
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 9 Jul 2021). 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?
Number of Dose Limiting Toxicity Events (time frame: Change from Baseline to Week 4). 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 9 Jul 2021.