Trial of Oxaloacetate in Alzheimer's Disease (TOAD)

NCT02593318 | Completed Phase 1 Results DMC

• 1 other identifier: STUDY00002242
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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).

Conditions

Alzheimer's Disease (AD)

Keywords

energy metabolism; oxaloacetate

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (4)

• Change in Brain Glucose Metabolic Rate as Determined by Fluorodeoxyglucose Positron Emission Tomography (FDG PET)

  Change from Baseline to Week 4

• Change in Brain Lactate Levels as Determined by 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

  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

  Change from dose to 60 min post dose and 90 min post dose

Study Arms (2)

Part 1 - Oxaloacetate (OAA) 1 gram/day

EXPERIMENTAL

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

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

Drug: Oxaloacetate (OAA) 2g

Interventions

Oxaloacetate (OAA) 1g DRUG

Pills to be taken orally in 500mg dose two times per day

Also known as: Oxobutanedioic acid, Oxaloacetic acid, Oxalacetic acid, 2-Oxosuccinic acid, Ketosuccinic acid

Part 1 - Oxaloacetate (OAA) 1 gram/day

Oxaloacetate (OAA) 2g DRUG

Pills to be taken orally in 1000mg dose two times per day.

Also known as: Oxobutanedioic acid, Oxaloacetic acid, Oxalacetic acid, 2-Oxosuccinic acid, Ketosuccinic acid

Part 2 - Oxaloacetate (OAA)2 gram/day

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Russell Swerdlow: lead

Study Sites (1)

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Oxaloacetic Acid

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Oxaloacetates; Oxalates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals; Keto Acids

Results Point of Contact

• Title: Russell H. Swerdlow, MD
• Organization: University of Kansas Medical Center

rswerdlow@kumc.edu

9135885000

Study Officials

• Russell Swerdlow, MD

  University of Kansas Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Gene and Marge Sweeney Professor of Neurology

Study Record Dates

• First Submitted: October 8, 2015
• First Posted: November 2, 2015
• Study Start: October 1, 2015
• Primary Completion: September 1, 2018
• Study Completion: September 1, 2018
• Last Updated: July 9, 2021
• Results First Posted: July 9, 2021

Record last verified: 2021-06

Locations

US (1)