Samuel T Henderson1, Bruce H Morimoto1, Jeffrey L Cummings2,3, Martin R Farlow4, Judith Walker1. 1. Cerecin, Inc, Denver, CO, USA and Singapore. 2. Department of Brain Health, School of Integrated Health Sciences, University of Nevada, Las Vegas (UNLV), Las Vegas, NV, USA. 3. Cleveland Clinic Lou Ruvo Center for Brain Health, Las Vegas, NV, USA. 4. Department of Neurology, Indiana University School of Medicine, Indianapolis, IN, USA.
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, NCT01741194), 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.
RCT Entities:
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, NCT01741194), 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.
Authors: Elidie Beard; Sylvain Lengacher; Sara Dias; Pierre J Magistretti; Charles Finsterwald Journal: Front Physiol Date: 2022-01-11 Impact factor: 4.566