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

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ClinicalTrials.gov Identifier: NCT03061474
Recruitment Status : Recruiting
First Posted : February 23, 2017
Last Update Posted : May 3, 2021
Sponsor:
Information provided by (Responsible Party):
Joshua Grill, University of California, Irvine

Tracking Information
First Submitted Date  ICMJE February 13, 2017
First Posted Date  ICMJE February 23, 2017
Last Update Posted Date May 3, 2021
Actual Study Start Date  ICMJE July 12, 2017
Estimated Primary Completion Date July 30, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: February 17, 2017)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: February 17, 2017)
  • 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.
  • 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.
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Nicotinamide as an Early Alzheimer's Disease Treatment
Official Title  ICMJE 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
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.
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)

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking Description:
Double-Blind-Randomized
Primary Purpose: Treatment
Condition  ICMJE
  • Alzheimer's Disease
  • Mild Cognitive Impairment
Intervention  ICMJE
  • Drug: Nicotinamide
    Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.
    Other Name: Niacinamide
  • Drug: Placebo Comparator
    Oral Tablet
Study Arms  ICMJE
  • Experimental: Nicotinamide
    1500mg twice daily: 2, 750mg tablets taken orally twice daily
    Intervention: Drug: Nicotinamide
  • Placebo Comparator: Placebo
    1500mg twice daily: 2, 750mg tablets taken orally twice daily
    Intervention: Drug: Placebo Comparator
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 17, 2017)
48
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 30, 2022
Estimated Primary Completion Date July 30, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 50 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Joshua Grill, Ph.D. 949-824-5905 jgrill@uci.edu
Contact: Megan Witbracht, Ph.D. 949-824-3249 mwitbrac@uci.edu
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03061474
Other Study ID Numbers  ICMJE 2016-3246
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Responsible Party Joshua Grill, University of California, Irvine
Study Sponsor  ICMJE University of California, Irvine
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Joshua Grill, Ph.D. Associate Professor of Psychiatry and Human Behavior
PRS Account University of California, Irvine
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP