drugset / Trial / NCT03061474
Nicotinamide as an Early Alzheimer's Disease Treatment
RandomizedParallel-groupTriple-blindTreatment
Summary
The purpose of this research study is to test whether nicotinamide, also known as vitamin B3 or niacinamide, taken in high doses, can reduce phosphorylation of tau (the protein that accumulates in neurofibrillary tangles) in people with Mild Cognitive Impairment or mild Alzheimer's disease (AD) dementia.
Timeline
- Start
- 2017-07-12
- Primary completion
- 2022-08-30
- Completion
- 2022-08-30
Outcome
Missed primary endpoint
registry analysis (superiority test); Nicotinamide vs Placebo; p = 0.6096; ANCOVA NCT03061474 ↗
paper There was no statistically significant benefit of nicotinamide on the primary outcome of week 48 change from baseline in CSF p-tau231 PMID 39671543 ↗
Publications
- Background Green KN, Steffan JS, Martinez-Coria H, Sun X, Schreiber SS, Thompson LM, LaFerla FM. Nicotinamide restores cognition in Alzheimer's disease transgenic mice via a mechanism involving sirtuin inhibition and selective reduction of Thr231-phosphotau. J Neurosci. 2008 Nov 5;28(45):11500-10. doi: 10.1523/JNEUROSCI.3203-08.2008.
- Background Liu D, Pitta M, Jiang H, Lee JH, Zhang G, Chen X, Kawamoto EM, Mattson MP. Nicotinamide forestalls pathology and cognitive decline in Alzheimer mice: evidence for improved neuronal bioenergetics and autophagy procession. Neurobiol Aging. 2013 Jun;34(6):1564-80. doi: 10.1016/j.neurobiolaging.2012.11.020. Epub 2012 Dec 25.
- Ketron GL, Grun F, Grill JD, Feldman HH, Rissman RA, Brewer GJ. Pharmacokinetic and pharmacodynamic assessment of oral nicotinamide in the NEAT clinical trial for early Alzheimer's disease. Alzheimers Res Ther. 2025 Mar 11;17(1):59. doi: 10.1186/s13195-025-01693-y.
- Grill JD, Tam S, Thai G, Vides B, Pierce AL, Green K, Gillen DL, Teng E, Kremen S, Beigi M, Rissman RA, Leger GC, Balasubramanian A, Revta C, Morrison R, Jennings R, Pa J, Zhang J, Jin S, Messer K, Feldman HH. Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease. Neurology. 2025 Jan 14;104(1):e210152. doi: 10.1212/WNL.0000000000210152. Epub 2024 Dec 13.
Drugs
| Evaluation | Drug | Modality | Dose | Route |
|---|---|---|---|---|
| Subject | Nicotinamide | Other / unclassified | 1500 mg | Oral |