TRIAL OF OXALOACETATE IN ALZHEIMER’S DISEASE (TOAD): INTERIM FDG PET ANALYSIS

Abstract

Brain bioenergetic function is defective in AD, and may contribute to reduced glucose utilization on fluorodeoxyglucose positron emission tomography (FDG PET) scans. Preclinical studies found oxaloacetate (OAA) enhanced brain bioenergetics and glucose flux, but human pharmacokinetic (PK) and pharmacodynamic (PD) data are lacking. The “Trial of Oxaloacetate in Alzheimer's Disease” (TOAD) study was designed to evaluate the PK and PD effects of 500 mg and 1000 mg OAA doses on AD participants. We obtained FDG PET scans on AD participants prior to starting a one month 500 mg twice daily (n=14) or 1000 mg twice daily (n=7) treatment intervention. We also obtained post-intervention FDG PET scans. We quantified the FDG PET signal from 7 different regions of interest (ROIs), and compared regional pre and post-intervention values. In 6 of the 7 FDG PET ROIs, relative to the 500 mg twice daily group the 1000 mg twice daily group trended towards a favorable response (either increased FDG PET signal at 1 month, or less decline at 1 month). Participants in the 1000 mg twice daily group showed a significant 2.5% increase in their hippocampal signal (p<0.05, paired T-test, nominal). The mean change in the 1000 mg twice daily group (2.5% mean increase, 0.9% standard error) also exceeded the mean change of the 500 mg twice daily group (0.3% mean decline, 0.7% standard error) (p<0.05, unpaired T-test). This TOAD study interim analysis suggests OAA at 1000 mg twice daily may engage brain bioenergetic metabolism. Whether or not positive findings persist at the conclusion of this study remains to be seen.