Clinical trial NCT02593318: Trial of Oxaloacetate in Alzheimer's Disease (TOAD)
Official title: Trial of Oxaloacetate in Alzheimer's Disease (TOAD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Alzheimer's Disease (AD)
Keywords: energy metabolism
oxaloacetate
Lead sponsor: University of Kansas Medical Center
Sponsor class: OTHER
First posted: 2015-11-01
Enrollment: 32
Sex: ALL
Minimum age (years): 50
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Number of Dose Limiting Toxicity Events
timeFrame: Change from Baseline to Week 4
Secondary outcomes:
measure: Change in Brain Glucose Metabolic Rate as Determined by Fluorodeoxyglucose Positron Emission Tomography (FDG PET)
timeFrame: Change from Baseline to Week 4
measure: Change in Brain Lactate Levels as Determined by Magnetic Resonance Spectroscopy (MRS)
timeFrame: Change from Baseline to Week 4
measure: Plasma Levels in 500 mg Bid Cohort at Baseline, 60 and 90 Minutes Post-Dose
timeFrame: Change from dose to 60 min post dose and 90 min post dose
measure: Plasma Levels in 1000 mg Bid Cohort at Baseline, 60 and 90 Minutes Post-Dose
timeFrame: Change from dose to 60 min post dose and 90 min post dose
Other outcomes:
Locations:
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
Study officials:
affiliation: University of Kansas Medical Center
name: Russell Swerdlow, MD
role: PRINCIPAL_INVESTIGATOR
References: