Trial reportNeurology2025
Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease.
Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase IIMulticenter Study
In one paragraph
Trial report in Neurology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03061474 (A Double-Blind-Randomized, Placebo-Controlled Adaptive Design Trial of Nicotinamide in Mild Cognitive Impairment Due to Alzheimer's Disease and Mild Alzheimer's Disease Dementia), which is not on this map. Cited by 9 papers, 1 of them a synthesis that pooled it.
0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed, 1 pooled it
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Double-Blind-Randomized, Placebo-Controlled Adaptive Design Trial of Nicotinamide in Mild Cognitive Impairment Due to Alzheimer's Disease and Mild Alzheimer's Disease Dementia
Who cites it
9 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Domain-specific effects of NADFrontiers in nutrition · 2026Pooled it
- Pharmacokinetic and pharmacodynamic assessment of oral nicotinamide in the NEAT clinical trial for early Alzheimer's disease.Alzheimer's research & therapy · 2025Trial
- SIRT1 in brain aging: molecular mechanisms and therapeutic potential of pharmacological and natural modulators.Biogerontology · 2026Review
- Early, sex-dependent and progressive proteomic imbalance in the amygdala during Alzheimer´s disease continuum.Biology of sex differences · 2026Article
- NADAlzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Vitamin deficiencies and Alzheimer's disease: evidence and implications for supplementation.Frontiers in nutrition · 2026Review
- Revisiting the therapeutic landscape of tauopathies: assessing the current pipeline and clinical trials.Alzheimer's research & therapy · 2025Review
- Recent Advances in Drug Development for Alzheimer's Disease: A Comprehensive Review.International journal of molecular sciences · 2025Review
- Autophagy-NADFrontiers in molecular biosciences · 2025Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
21 authors.
Joshua D GrillFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0000-0002-4215-7589
Steven TamFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0009-0008-7347-0958
Gaby ThaiFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0009-0006-9594-7492
Beatriz VidesFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0009-0000-5396-7213
Aimee L PierceFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0000-0002-9423-366X
Kim GreenFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0000-0002-6049-6744
Daniel L GillenFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0000-0003-1983-9730
Edmond TengFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.
Sarah KremenFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0000-0003-2593-0602
Maryam BeigiFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0000-0002-4070-2109
Robert A RissmanFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0000-0001-9245-8278
Gabriel C LégerFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0000-0001-7900-3957
Archana BalasubramanianFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0009-0007-8688-3156
Carolyn RevtaFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0009-0007-3162-5870
Rosemary MorrisonFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.
Robin JenningsFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0009-0004-2125-7638
Judy PaFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0000-0002-5788-9352
Jing ZhangFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0000-0002-1578-3760
Shelia JinFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0009-0002-0055-6669
Karen MesserFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0000-0002-9298-2413
Howard H FeldmanFrom the Institute for Memory Impairments and Neurological Disorders (J.D.G., S.T., G.T., B.V., K.G., D.L.G.), University of California, Irvine; Department of Psychiatry and Human Behavior (J.D.G.), University of California, Irvine; Department of Neurobiology and Behavior (J.D.G., K.G.), University of California, Irvine; Division of Geriatric Medicine (S.T.), Department of Medicine, University of California, Irvine; Department of Neurology (G.T.), University of California, Irvine; Department of Neurology (A.L.P.), Oregon Health and Science University; Department of Statistics (D.L.G.), University of California, Irvine; Department of Neurology and Neurological Sciences (E.T.), Stanford University; Department of Neurology (S.K.), Cedars Sinai Medical Center; Department of Neurology (M.B.), University of California, Los Angeles; Alzheimer's Disease Cooperative Study (R.A.R., G.C.L., A.B., C.R., R.M., R.J., J.P., J.Z., S.J., K.M., H.H.F.), University of California, San Diego; and Department of Neurosciences (G.C.L., J.P., H.H.F.), University of California, San Diego.ORCID 0000-0002-9258-4538
Funding
Research Education ComponentP30AG066518 · NIA · OREGON HEALTH & SCIENCE UNIVERSITY · PI KEVIN M DUFF, Lisa C Silbert · 2020 to 2026
$28.6MUSCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI · 2020 to 2026
$27.8MNIA NIH HHS P30 AG066518NIA NIH HHS P30 AG066530
Abstract
BACKGROUND AND
objectivesNicotinamide 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).
methodsWe performed a randomized, placebo-controlled, phase 2a proof-of-concept trial to evaluate the safety and tolerability of 48 weeks of treatment with 1,500 mg of nicotinamide twice a day. The primary outcome was level of tau phosphorylated at threonine 231 (p-tau
resultsOf 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. Adverse events (AEs) were balanced by arm, with few attributed to treatment. Common AEs included infections and nervous system disorders. There was no statistically significant benefit of nicotinamide on the primary outcome of week 48 change from baseline in CSF p-tau DISCUSSION: Nicotinamide was safe but did not alter AD biomarkers. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that in patients with MCI or mild dementia with positive CSF AD biomarkers, 48 weeks of nicotinamide, 3,000 mg daily, is no better than placebo in reducing CSF p-tau TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov: NCT03061474.
Indexed as
Alzheimer DiseaseNiacinamidetau ProteinsAgedAged, 80 and overAmyloid beta-PeptidesBiomarkersDouble-Blind MethodFemaleHumansMaleMiddle AgedPeptide FragmentsPhosphorylationProof of Concept StudyTreatment OutcomeAmyloid beta-Peptidesamyloid beta-protein (1-42)BiomarkersNiacinamidePeptide Fragmentstau ProteinsVitamin B Complex
Identifiers
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Read underepoch 390
Registered trials
NCT03061474ClinicalTrials.gov
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.