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

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ClinicalTrials.gov Identifier: NCT02593318
Recruitment Status : Completed
First Posted : November 2, 2015
Last Update Posted : October 12, 2018
Sponsor:
Information provided by (Responsible Party):
Russell Swerdlow, MD, University of Kansas Medical Center

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).

Condition or disease Intervention/treatment Phase
Alzheimer's Disease (AD) Drug: Oxaloacetate (OAA) Phase 1

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 30 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Trial of Oxaloacetate in Alzheimer's Disease (TOAD)
Study Start Date : October 2015
Actual Primary Completion Date : September 2018
Actual Study Completion Date : September 2018

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1 - Oxaloacetate (OAA) 1 gram/day
Participants take 1 gram of OAA per day for period of 4 weeks
Drug: Oxaloacetate (OAA)
Pills to be taken orally in 500mg or 1000mg doses two times per day depending on the part of the study
Other Names:
  • Oxobutanedioic acid
  • Oxaloacetic acid
  • Oxalacetic acid
  • 2-Oxosuccinic acid
  • Ketosuccinic acid

Experimental: Part 2 - Oxaloacetate (OAA)2 gram/day
Participants take 2 grams of OAA per day for period of 4 weeks
Drug: Oxaloacetate (OAA)
Pills to be taken orally in 500mg or 1000mg doses two times per day depending on the part of the study
Other Names:
  • Oxobutanedioic acid
  • Oxaloacetic acid
  • Oxalacetic acid
  • 2-Oxosuccinic acid
  • Ketosuccinic acid




Primary Outcome Measures :
  1. Change in Safety Assessments (safety labs, physical and neurological exams, vital signs, cognitive measures, signs and symptoms) [ Time Frame: Change from Baseline to Week 4 ]
    Change in safety labs, physical and neurological exams, vital signs, cognitive measures, signs and symptoms


Secondary Outcome Measures :
  1. Change in brain glucose metabolic rate as determined by Fluorodeoxyglucose positron emission tomography (FDG PET) [ Time Frame: Change from Baseline to Week 4 ]
    Fluorodeoxyglucose positron emission tomography (FDG PET)

  2. Change in brain lactate levels as determined by magnetic resonance spectroscopy (MRS) [ Time Frame: Change from Baseline to Week 4 ]
    magnetic resonance spectroscopy (MRS)

  3. Correlation between oral OAA intake and plasma levels in 500 mg bid cohort [ Time Frame: Change from dose to 60 min post dose and 90 min post dose ]
    For the 1 g/ day (500 mg bid) cohort, baseline blood sample will be obtained before 500 mg OAA is administered. Blood samples to be drawn again at 60 min and 90 min post administration of dose.

  4. Correlation between oral OAA intake and plasma levels in 1000 mg bid cohort [ Time Frame: Change from dose to 60 min post dose and 90 min 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.



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02593318


Locations
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United States, Kansas
University of Kansas Medical Center
Kansas City, Kansas, United States, 66160
Sponsors and Collaborators
Russell Swerdlow, MD
Investigators
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Principal Investigator: Russell Swerdlow, MD University of Kansas Medical Center

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Responsible Party: Russell Swerdlow, MD, Gene and Marge Sweeney Professor of Neurology, University of Kansas Medical Center
ClinicalTrials.gov Identifier: NCT02593318     History of Changes
Other Study ID Numbers: STUDY00002242
First Posted: November 2, 2015    Key Record Dates
Last Update Posted: October 12, 2018
Last Verified: October 2018

Keywords provided by Russell Swerdlow, MD, University of Kansas Medical Center:
energy metabolism
oxaloacetate

Additional relevant MeSH terms:
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Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders