NEAT: Nicotinamide as an Early Alzheimer's Disease Treatment

Sponsor

University of California, Irvine (Other)

Overall Status

Active, not recruiting

CT.gov ID

NCT03061474

Collaborator

(none)

Enrollment

Locations

Arms

61.6

Anticipated Duration (Months)

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

Study Description

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)

Study Design

Study Type:

Interventional

Anticipated 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 :

Jul 12, 2017

Anticipated Primary Completion Date :

Aug 30, 2022

Anticipated Study Completion Date :

Aug 30, 2022

Arms and Interventions

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

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 Names:

Niacinamide

Placebo Comparator: Placebo

1500mg twice daily: 2, 750mg tablets taken orally twice daily

Drug: Placebo Comparator

Oral Tablet

Outcome Measures

Primary Outcome Measures

Change in p-tau 231 [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

Change in p-tau 181 [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 [12 Months]
Change in CSF total tau in individuals with mild Alzheimer's disease (AD) dementia or Mild Cognitive Impairment due to AD.

Eligibility Criteria

Criteria

Ages Eligible for Study:

50 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

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

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

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

Exclusion Criteria:

Active neurological or psychiatric diagnosis other than AD that may affect cognition and/or function. (Obstructive sleep apnea is permitted, if treated.)
Inability to undergo lumbar puncture, including use of Coumadin, novel oral anticoagulants, clopidogrel, or dipyridamole. Use of aspirin <= 325mg daily is permitted.
Hachinski ischemic scale > 4
Magnetic Resonance Imaging (MRI) incompatibility
MRI evidence of cortical stroke >1cm, superficial siderosis, or extensive white matter hyperintensity (Cardiovascular Health Study score 7-8+)
Diagnosis of cancer in the previous 5 years (with the exception of basal or squamous cell carcinoma)
Geriatric Depression Scale (GDS) score >6
History within the past 5 years of alcohol or substance use disorder
Laboratory evidence of a clinically significant abnormality that may interfere with study assessments
Active partial or total malabsorptive disease (e.g., celiac disease)
Resides in a skilled nursing facility
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)
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).
Unwillingness to abstain from over-the-counter nicotinamide for the duration of the trial