Evidence map›Paper›PMID 40069789›Full record

Trial reportAlzheimer's research & therapy2025

Pharmacokinetic and pharmacodynamic assessment of oral nicotinamide in the NEAT clinical trial for early Alzheimer's disease.

Gabriel L Ketron, Felix Grun, Joshua D Grill, Howard H Feldman, Robert A Rissman, Gregory J Brewer

Registry-linked trialAbstract readRandomized Controlled TrialClinical Trial, Phase IIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Alzheimer's research & therapy, 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 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

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.

2 · The registry

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.

NCT03061474 phase2completednot on this map

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

TypeinterventionalSponsorUniversity of California, IrvineRan2017 to 2022Enrolled46ConditionsAlzheimer's Disease, Mild Cognitive ImpairmentArmsNicotinamide, Placebo Comparator
3 · Its place in the literature

Who cites it

4 citing papers in PubMed.

  1. Article
  2. Article
  3. Update on Nicotinamide and Its Application in the Management of Glaucoma.International journal of molecular sciences · 2025
    Review
  4. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

Gabriel L KetronDepartment of Biomedical Engineering, University of California, Irvine, CA, USA.
Felix GrunDepartment of Chemistry, University of California, Irvine, CA, USA.
Joshua D GrillInstitute for Memory Impairments and Neurological Disorders, University of California, Irvine, CA, USA.
Howard H FeldmanDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Robert A RissmanDepartment of Neurosciences, University of California San Diego, La Jolla, CA, USA.
Gregory J BrewerDepartment of Biomedical Engineering, University of California, Irvine, CA, USA. GJBrewer@uci.edu.

Funding

USCADRC Diversity Supplement PachicanoP30AG066530 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI HELENA Chang CHUI · 2020 to 2026
$27.8M
Alzheimer's Association Zenith Award . #1066394NIA NIH HHS P30 AG066530UC Cures BRD-16-501530
6 · The paper itself

Abstract

backgroundNicotinamide, a form of B3 vitamin, is an NAD

methodsIn these post hoc, blinded analyses of plasma and CSF samples from the completed two-site placebo controlled randomized trial testing of 1500 mg PO BID oral nicotinamide, we used mass spectroscopy to measure nicotinamide and its inactive metabolite 1-methyl-nicotinamide in plasma at baseline, 6, and 12 months and in CSF at baseline and 12 months from 23 participants on drug and 24 on placebo.

resultsPharmacokinetic analysis found mean 12 month plasma nicotinamide increased > 130-fold to 52 μM while mean methyl-nicotinamide increased > 600-fold to 91 μM in individuals receiving nicotinamide compared to those receiving placebo, whose levels were unchanged from baseline. However, CSF nicotinamide was only measurable in 6 of the 19 available participants (32%) (mean increase of at least 147-fold to 18 μM). These CSF nicotinamide concentrations were 66% of their plasma levels, indicating good CNS bioavailability in only some participants. In contrast to CSF nicotinamide, more treated participants had higher CSF methyl-nicotinamide (n = 9, 43 μM), suggesting high-dosage nicotinamide was sufficient to pass the blood-brain barrier, but 13 of 19 were metabolically inactivated. Treatment favorably decreased mean pTau

conclusionsOur findings suggest that oral administration markedly increased mean plasma nicotinamide levels, however CSF levels were below quantitation in a majority of participants and there was extensive metabolic inactivation to methyl-nicotinamide. Both the bioavailability and rapid metabolic methylation need to be addressed if nicotinamide is further developed as a potential intervention for AD.

trial registrationNCT03061474, last updated 2023-10-17. https://clinicaltrials.gov/study/NCT03061474 .

Indexed as

Alzheimer DiseaseNiacinamideAdministration, OralAgedBiomarkersDouble-Blind MethodFemaleHumansMaleMiddle Agedtau ProteinsBiomarkersMAPT protein, humanNiacinamidetau ProteinsAlzheimer disease clinical trialCSFMethyl-nicotinamideNicotinamidePharmacokineticsPlasmaPtau231

Identifiers

PMID40069789
PMCPMC11895359

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

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.