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Nicotinamide as an Early Alzheimer's Disease Treatment (NEAT)

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ClinicalTrials.gov Identifier: NCT03061474
Recruitment Status : Active, not recruiting
First Posted : February 23, 2017
Last Update Posted : November 16, 2021
Information provided by (Responsible Party):
Joshua Grill, University of California, Irvine

Brief 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.

Condition or disease Intervention/treatment Phase
Alzheimer's Disease Mild Cognitive Impairment Drug: Nicotinamide Drug: Placebo Comparator Phase 2

Detailed Description:

Nicotinamide, the amide of nicotinic acid (vitamin B3/niacin), is an oral therapy with a wealth of clinical data in a variety of therapeutic areas, including preliminary data supporting its safety in Alzheimer's disease (AD). Preclinical work in a mouse model that develops both plaques and tangles supports the hypothesis that nicotinamide can act as a histone deacetylase (HDAC) inhibitor to reduce phosphorylation of tau.

The study will implement a group sequential design, incorporating a futility analysis with a go/no-go decision conditional on cerebral spinal fluid CSF biomarker outcomes at 12-months. The primary outcome for the trial is change in p-tau231.

This study timeline includes a screening phase of up to 60 days and treatment phase which is expected to last about 48 weeks and will include 4 study visits.

An additional 12-month treatment and follow-up period is planned, contingent upon a "go" decision based on the primary outcome (CSF p-tau231) or one planned secondary outcome (CSF p-tau181)

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 48 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description: Double-Blind-Randomized
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : July 12, 2017
Estimated Primary Completion Date : August 30, 2022
Estimated Study Completion Date : August 30, 2022

Arm Intervention/treatment
Experimental: Nicotinamide
1500mg twice daily: 2, 750mg tablets taken orally twice daily
Drug: Nicotinamide
Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.
Other Name: Niacinamide

Placebo Comparator: Placebo
1500mg twice daily: 2, 750mg tablets taken orally twice daily
Drug: Placebo Comparator
Oral Tablet

Primary Outcome Measures :
  1. Change in p-tau 231 [ Time Frame: 12 Months ]
    Change in CSF phosphorylated tau (p-tau231) in individuals with mild Alzheimer's disease (AD) dementia or Mild Cognitive Impairment due to AD.

Secondary Outcome Measures :
  1. Change in p-tau 181 [ Time Frame: 12 Months ]
    Change in CSF phosphorylated tau (p-tau181) in individuals with mild Alzheimer's disease (AD) dementia or Mild Cognitive Impairment due to AD.

  2. Change in total tau [ Time Frame: 12 Months ]
    Change in CSF total tau in individuals with mild Alzheimer's disease (AD) dementia or Mild Cognitive Impairment due to AD.

Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  1. Mild Cognitive Impairment (MCI) or dementia due to Alzheimer's disease (AD)
  2. Biomarker criteria:

    Cerebral Spinal Fluid (CSF) Amyloid Beta 1-42 (Aβ42) <= 600 pg/mL, or A ratio of total tau to Aβ42 ≥ 0.39.

  3. Mini-Mental State Exam (MMSE) ≥ 20
  4. Blood laboratories, urinalysis, and electrocardiogram are within normal limits or deemed clinically not significant by the site investigator
  5. Stable medications (including approved AD therapies) for at least 4 weeks
  6. At least 6 years of education
  7. Able to swallow oral tablets
  8. Speaks English fluently
  9. Available qualified study partner (≥3 times per week in-person communication with the participant)

Exclusion Criteria:

  1. Active neurological or psychiatric diagnosis other than AD that may affect cognition and/or function. (Obstructive sleep apnea is permitted, if treated.)
  2. Inability to undergo lumbar puncture, including use of Coumadin, novel oral anticoagulants, clopidogrel, or dipyridamole. Use of aspirin <= 325mg daily is permitted.
  3. Hachinski ischemic scale > 4
  4. Magnetic Resonance Imaging (MRI) incompatibility
  5. MRI evidence of cortical stroke >1cm, superficial siderosis, or extensive white matter hyperintensity (Cardiovascular Health Study score 7-8+)
  6. Diagnosis of cancer in the previous 5 years (with the exception of basal or squamous cell carcinoma)
  7. Geriatric Depression Scale (GDS) score >6
  8. History within the past 5 years of alcohol or substance use disorder
  9. Laboratory evidence of a clinically significant abnormality that may interfere with study assessments
  10. Active partial or total malabsorptive disease (e.g., celiac disease)
  11. Resides in a skilled nursing facility
  12. Participation in a clinical trial of a potential disease-modifying therapy for AD in previous 6-months (time between last investigational drug administration and baseline for the current study)
  13. Pregnant, lactating or of child bearing potential (that is, women must be 2 years post-menopausal or surgically sterile to be considered not child bearing potential).
  14. Unwillingness to abstain from over-the-counter nicotinamide for the duration of the trial

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03061474

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United States, California
University of California, Irvine
Irvine, California, United States, 92697
University of California, Los Angeles
Los Angeles, California, United States, 90095
Sponsors and Collaborators
University of California, Irvine
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Principal Investigator: Joshua Grill, Ph.D. Associate Professor of Psychiatry and Human Behavior
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Responsible Party: Joshua Grill, Associate Professor, Psychiatry & Human Behavior, University of California, Irvine
ClinicalTrials.gov Identifier: NCT03061474    
Other Study ID Numbers: 2016-3246
First Posted: February 23, 2017    Key Record Dates
Last Update Posted: November 16, 2021
Last Verified: November 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Joshua Grill, University of California, Irvine:
Mild Cognitive Impairment
Alzheimer's Disease
Nicotinic Acids
Neurodegenerative Diseases
Additional relevant MeSH terms:
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Alzheimer Disease
Cognitive Dysfunction
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Cognition Disorders
Nicotinic Acids
Vitamin B Complex
Physiological Effects of Drugs
Hypolipidemic Agents
Molecular Mechanisms of Pharmacological Action
Lipid Regulating Agents
Vasodilator Agents