Title

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

Document Type

Article

Publication Date

5-19-2020

Publication Title

Journal of Alzheimer's Disease

Volume

75

Issue

2

First page number:

547

Last page number:

557

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.

Keywords

Apolipoprotein E4; Clinical trial; Glucose; Ketone body; Ketosis; Metabolism

Disciplines

Medical Neurobiology | Nervous System Diseases

Language

English

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