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Record W4405352332 · doi:10.1212/wnl.0000000000210152

Phase 2A Proof-of-Concept Double-Blind, Randomized, Placebo-Controlled Trial of Nicotinamide in Early Alzheimer Disease

2024· article· en· W4405352332 on OpenAlexfundno aff
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

Bibliographic record

VenueNeurology · 2024
Typearticle
Languageen
FieldMedicine
TopicSirtuins and Resveratrol in Medicine
Canadian institutionsnot available
FundersOffice of the President, University of CaliforniaGenentechNovo NordiskArrowhead PharmaceuticalsEisaiConsortium canadien en neurodégénérescence associée au vieillissementUniversity of California, IrvineUniversity of California, San DiegoBiogenNational Institute on AgingEli Lilly and Company
KeywordsRandomized controlled trialDouble blindPlaceboMedicineNicotinamideDiseaseAlzheimer's diseaseInternal medicinePathologyAlternative medicinePhysics

Abstract

fetched live from OpenAlex

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.

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.

How this classification was reachedexpand

Full frame machine prediction

Teacher imitation

Not calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.

metaresearch head score (Codex)0.003
metaresearch head score (Gemma)0.002
Version: metacan-v3-hybrid-931329e0061cValidation status: machine_predicted_unvalidated
Candidate categoriesnone
Consensus categoriesnone
DomainCandidate signal: none · Consensus signal: none
Study designCandidate signal: Randomized trial · Consensus signal: Randomized trial
GenreCandidate signal: Empirical · Consensus signal: Empirical
Teacher disagreement score0.022
Threshold uncertainty score0.074

Distilled classifier scores by category (both heads)

CategoryCodexGemma
Metaresearch0.0030.002
Meta-epidemiology (narrow)0.0030.001
Meta-epidemiology (broad)0.0040.002
Bibliometrics0.0000.000
Science and technology studies0.0010.001
Scholarly communication0.0020.002
Open science0.0010.001
Research integrity0.0030.004
Insufficient payload (model declined to judge)0.0220.003

Machine scores (provisional)

The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.

Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.

Opus teacher head0.030
GPT teacher head0.335
Teacher spread0.304 · how far apart the two teachers sit on this one work
Validation statusscore_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from it

Classification

machine, unvalidated

Machine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.

The models applied no category: nothing in the taxonomy fit this work.
Study designRandomized trial
Domainnot available
GenreEmpirical

How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".

Quick stats

Citations16
Published2024
Admission routes1
Has abstractyes

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