Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease
Joshua D. Grill, Steven Tam, Gaby Thai, Beatriz Vides, Aimee Pierce, Kim N. Green, Daniel L. Gillen, Edmond Teng, Sarah Kremen, Maryam Beigi, Robert A. Rissman, Gabriel C. Léger, Archana Balasubramanian, Carolyn Revta, Rosemary Morrison, Robin G. Jennings, Judy Pa, Jing Zhang, Shelia Jin, Karen Messer, Howard Feldman
Abstract
BACKGROUND AND OBJECTIVES: Nicotinamide is a coenzyme involved in cellular oxidation-reduction reactions that can inhibit Class III histone deacetylases (HDACs) or sirtuins. HDAC inhibition can affect numerous therapeutic pathways, including tau phosphorylation. We tested the hypothesis that nicotinamide treatment could reduce tau phosphorylation in early Alzheimer disease (AD). METHODS: in CSF and the clinical measures Alzheimer's Disease Assessment Scale (ADAS-cog13), Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale-Mild Cognitive Impairment (ADCS-ADL-MCI), and Clinical Dementia Rating Summary of Boxes (CDR-SB). Participants were recruited at 2 academic clinical centers. Enrollment criteria included diagnosis of mild cognitive impairment or mild dementia with CSF biomarker confirmation of AD. The Holm-Bonferroni procedure was used to control type I error within biomarker and clinical domains. RESULTS: = 0.10) outcomes. DISCUSSION: Nicotinamide was safe but did not alter AD biomarkers. CLASSIFICATION OF EVIDENCE: . TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT03061474.