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Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease
Grill JD, Tam S, Thai G, Vides B, Pierce AL, Green K, Gillen DL, Teng E et al.. Neurology, 2024-12-13
Topic: Amyloid, tau and blood-test diagnosis
Results Of 47 participants enrolled (mean age = 73.8 years; 43% female), 1 dropped out before treatment initiation and 6 before completion, including 2 in the nicotinamide and 4 in the placebo arm. There was no statistically significant benefit of nicotinamide on the primary outcome of week 48 change from baseline in CSF p-tau 231 (analysis of covariance; estimated mean difference in change between arms = -2.06, SE = 4.03; p = 0.61), with observed mean decline in CSF p-tau 231 greater in the nicotinamide arm (-4.7 ± 14.5) than in the placebo arm (-2.3 ± 10.6). No significant effects of treatment were observed on secondary biomarker outcomes (CSF p-tau 181 , Aβ 40 , Aβ 42 , and total tau) in similar models (all p values >0.05), with observed mean changes in CSF p-tau 181 (0.4 ± 29.8 vs 10.4 ± 41.8) and total tau (8.4 ± 228.6 vs 60.5 ± 237.5) favoring nicotinamide compared with placebo. At week 48, nicotinamide-treated participants experienced less decline on CDR-SB (mixed-effect model with repeated measures; estimate = -1.42, SE = 0.65; p = 0.03 unadjusted for multiple comparisons), without significant differences in cognitive (ADAS-cog; estimate = -1.93, SE = 1.93; p = 0.32) or functional (ADCS-ADL-MCI; estimate = -3.10, SE = 1.86; p = 0.10) outcomes.
Key findings
- Results Of 47 participants enrolled (mean age = 73.8 years; 43% female), 1 dropped out before treatment initiation and 6 before completion, including 2 in the nicotinamide and 4 in the placebo arm.
- There was no statistically significant benefit of nicotinamide on the primary outcome of week 48 change from baseline in CSF p-tau 231 (analysis of covariance; estimated mean difference in change between arms = -2.06, SE = 4.03; p = 0.61), with observed mean decline in CSF p-tau 231 greater in the nicotinamide arm (-4.7 ± 14.5) than in the placebo arm (-2.3 ± 10.6).
- No significant effects of treatment were observed on secondary biomarker outcomes (CSF p-tau 181 , Aβ 40 , Aβ 42 , and total tau) in similar models (all p values >0.05), with observed mean changes in CSF p-tau 181 (0.4 ± 29.8 vs 10.4 ± 41.8) and total tau (8.4 ± 228.6 vs 60.5 ± 237.5) favoring nicotinamide compared with placebo.
- At week 48, nicotinamide-treated participants experienced less decline on CDR-SB (mixed-effect model with repeated measures; estimate = -1.42, SE = 0.65; p = 0.03 unadjusted for multiple comparisons), without significant differences in cognitive (ADAS-cog; estimate = -1.93, SE = 1.93; p = 0.32) or functional (ADCS-ADL-MCI; estimate = -3.10, SE = 1.86; p = 0.10) outcomes.
Why it matters
In this small 47-person trial, nicotinamide showed no significant benefit on the main biomarker outcome, and no significant effects on other biomarkers or on cognitive and functional measures. One measure of decline favored nicotinamide but was not adjusted for multiple comparisons, so the trial does not show that nicotinamide treats early Alzheimer's disease.
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Study details
- Participants47
- Evidence strengthHigh
How this study scored 68/100
Published in a leading specialty journal, and it is a randomised controlled trial. Scored zero for effect reported because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Neurology) |
| Journal's citation record | 4 / 4 | Neurology: journal h-index 525 (OpenAlex, 2026-10-29) |
| Study design | 11 / 12 | A randomised controlled trial (from PubMed type “Randomized Controlled Trial”) |
| Strength of evidence | 5 / 5 | Rated “high” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 1 / 4 | 47 participants |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 2 / 2 | Randomised and blinded or placebo-controlled (as stated in the record) |
| Times cited | 3 / 7 | Cited 21 times (OpenAlex, 2026-10-10) |
| Citations per year | 2 / 5 | 7.0 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 3 / 6 | Cited 5.0× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 2 / 4 | Cited 21 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 4 / 4 | Last-listed author Howard Feldman: h-index 105 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of California, Irvine: institution h-index 1,195 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | PubMed indexes it as a multicentre study |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 39671543) |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Total | 68 / 100 | — |
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Read the original
- DOI: 10.1212/wnl.0000000000210152
- PubMed: 39671543
- Original source →
- Free full text: PubMed Central →
Full text: free to read — PubMed Central lists this copy as free to read: the link above (checked 10 Oct 2026).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Grill, J. D., Tam, S., Thai, G., Vides, B., Pierce, A. L., Green, K., et al. (2025). Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease. Neurology. https://doi.org/10.1212/wnl.0000000000210152
Vancouver
Grill JD, Tam S, Thai G, Vides B, Pierce AL, Green K, et al. Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease. Neurology. 2025. doi:10.1212/wnl.0000000000210152. PMID: 39671543.
BibTeX
@article{grill2025-39671543,
author = {Grill, J. D. and Tam, S. and Thai, G. and Vides, B. and Pierce, A. L. and Green, K. and Gillen, D. L. and Teng, E. and others},
title = {{Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease}},
journal = {Neurology},
year = {2025},
doi = {10.1212/wnl.0000000000210152},
pmid = {39671543},
url = {https://doi.org/10.1212/wnl.0000000000210152}
}
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