Nicotinamide as an Early Alzheimer's Disease Treatment
Condition: Alzheimer's Disease; Mild Cognitive Impairment
MeSH terms: Alzheimer Disease; Cognitive Dysfunction
Intervention: Nicotinamide; Placebo Comparator
Intervention description: Niacinamide (nicotinamide; 99%) is produced in a 750 mg sustained release tablet.; Oral Tablet
Intervention MeSH terms: Niacinamide; Niacin; Nicotinic Acids
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Masking description: Double-Blind-Randomized
Enrollment: 46.0
Sex: All
Minimum age: 50 Years
Healthy volunteers: No
Keywords: Mild Cognitive Impairment; Alzheimer's Disease; Nicotinamide; Niacinamide; Niacin; Nicotinic Acids; Vitamin; Neurodegenerative Diseases; Tauopathies; Dementia

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.
    

Eligibility criteria:

        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