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Trial of Oxaloacetate in Alzheimer's Disease (TOAD) (TOAD)

Primary Purpose

Alzheimer's Disease (AD)

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Oxaloacetate (OAA) 1g
Oxaloacetate (OAA) 2g
Sponsored by
Russell Swerdlow
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alzheimer's Disease (AD) focused on measuring energy metabolism, oxaloacetate

Eligibility Criteria

50 Years - 85 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • 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)

Exclusion Criteria:

  • 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;
  • 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

Sites / Locations

  • University of Kansas Medical Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

Part 1 - Oxaloacetate (OAA) 1 gram/day

Part 2 - Oxaloacetate (OAA)2 gram/day

Arm Description

Participants take 1 gram of OAA per day for period of 4 weeks

Participants take 2 grams of OAA per day for period of 4 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Change in Brain Glucose Metabolic Rate as Determined by Fluorodeoxyglucose Positron Emission Tomography (FDG PET)
Fluorodeoxyglucose positron emission tomography (FDG PET)
Change in Brain Lactate Levels as Determined by Magnetic Resonance Spectroscopy (MRS)
magnetic resonance spectroscopy (MRS)
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.
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.

Full Information

First Posted
October 8, 2015
Last Updated
June 17, 2021
Sponsor
Russell Swerdlow
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1. Study Identification

Unique Protocol Identification Number
NCT02593318
Brief Title
Trial of Oxaloacetate in Alzheimer's Disease (TOAD)
Acronym
TOAD
Official Title
Trial of Oxaloacetate in Alzheimer's Disease (TOAD)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2021
Overall Recruitment Status
Completed
Study Start Date
October 2015 (undefined)
Primary Completion Date
September 2018 (Actual)
Study Completion Date
September 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Russell Swerdlow

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alzheimer's Disease (AD)
Keywords
energy metabolism, oxaloacetate

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Part 1 - Oxaloacetate (OAA) 1 gram/day
Arm Type
Experimental
Arm Description
Participants take 1 gram of OAA per day for period of 4 weeks
Arm Title
Part 2 - Oxaloacetate (OAA)2 gram/day
Arm Type
Experimental
Arm Description
Participants take 2 grams of OAA per day for period of 4 weeks
Intervention Type
Drug
Intervention Name(s)
Oxaloacetate (OAA) 1g
Other Intervention Name(s)
Oxobutanedioic acid, Oxaloacetic acid, Oxalacetic acid, 2-Oxosuccinic acid, Ketosuccinic acid
Intervention Description
Pills to be taken orally in 500mg dose two times per day
Intervention Type
Drug
Intervention Name(s)
Oxaloacetate (OAA) 2g
Other Intervention Name(s)
Oxobutanedioic acid, Oxaloacetic acid, Oxalacetic acid, 2-Oxosuccinic acid, Ketosuccinic acid
Intervention Description
Pills to be taken orally in 1000mg dose two times per day.
Primary Outcome Measure Information:
Title
Number of Dose Limiting Toxicity Events
Description
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.
Time Frame
Change from Baseline to Week 4
Secondary Outcome Measure Information:
Title
Change in Brain Glucose Metabolic Rate as Determined by Fluorodeoxyglucose Positron Emission Tomography (FDG PET)
Description
Fluorodeoxyglucose positron emission tomography (FDG PET)
Time Frame
Change from Baseline to Week 4
Title
Change in Brain Lactate Levels as Determined by Magnetic Resonance Spectroscopy (MRS)
Description
magnetic resonance spectroscopy (MRS)
Time Frame
Change from Baseline to Week 4
Title
Plasma Levels in 500 mg Bid Cohort at Baseline, 60 and 90 Minutes Post-Dose
Description
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.
Time Frame
Change from dose to 60 min post dose and 90 min post dose
Title
Plasma Levels in 1000 mg Bid Cohort at Baseline, 60 and 90 Minutes Post-Dose
Description
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.
Time Frame
Change from dose to 60 min post dose and 90 min post dose

10. Eligibility

Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
85 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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) Exclusion Criteria: 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; 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Russell Swerdlow, MD
Organizational Affiliation
University of Kansas Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
University of Kansas Medical Center
City
Kansas City
State/Province
Kansas
ZIP/Postal Code
66160
Country
United States

12. IPD Sharing Statement

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Trial of Oxaloacetate in Alzheimer's Disease (TOAD)

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