A Placebo-Controlled, Parallel-Group, Randomized Clinical Trial of AC-1204 in Mild-To-Moderate Alzheimer's Disease

Samuel T. Henderson, Bruce H. Morimoto, Jeffrey L. Cummings, Martin R. Farlow, Judith Walker

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Alzheimer's disease (AD) is characterized by amyloid-β plaques, neurofibrillary tangles, and regional cerebral glucose hypometabolism. Providing an alternative metabolic substrate, such as ketone bodies, may be a viable therapeutic option. Objective: The objective was to determine the efficacy and safety of the AC-1204 formulation of caprylic triglyceride administered daily for 26 weeks in APOE4 non-carrier participants with mild-To-moderate AD. Methods: In a double-blind, placebo-controlled, randomized study (AC-12-010, NOURISH AD, NCT 01741194), 413 patients with mild-To-moderate probable AD were stratified by APOE genotype and randomized (1:1) to receive either placebo or AC-1204 for 26 weeks. The primary outcome was the change from baseline to week 26 on the 11-item Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog11) among APOE4 non-carriers. The key secondary outcome was the change from baseline to week 26 in the Alzheimer's Disease Cooperative Study-Clinician's Global Impression of Change scale. Results: Administration of AC-1204 was safe and well-Tolerated. Mean changes from baseline in the primary outcome at 26 weeks in ADAS-Cog11 for placebo (n=138) was 0.0 and for AC-1204 (n=137) was 0.6 (LS differences of mean-0.761, p=0.2458) and secondary outcome measures failed to detect any drug effects. Conclusion: The AC-1204 formulation of caprylic triglyceride failed to improve cognition or functional ability in subjects with mild-To-moderate AD. The lack of efficacy observed in this study may have several contributing factors including a lower ketone body formation from AC-1204 than expected and a lack of decline in the patients receiving placebo.

Original languageEnglish (US)
Pages (from-to)547-557
Number of pages11
JournalJournal of Alzheimer's Disease
Volume75
Issue number2
DOIs
StatePublished - Jan 1 2020

Keywords

  • Apolipoprotein E4
  • clinical trial
  • glucose
  • ketone body
  • ketosis
  • metabolism

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Psychology
  • Geriatrics and Gerontology
  • Psychiatry and Mental health

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