This Phase 1/2 clinical trial (NCT06582706) evaluates extended-release niacin (vitamin B3) as a potential treatment for Alzheimer's disease (AD)[1]. Niacin (nicotinic acid) is a precursor to NAD+ (nicotinamide adenine dinucleotide), a critical coenzyme that becomes depleted in the aging brain and is particularly deficient in neurodegenerative conditions.
This trial represents a metabolic approach to AD treatment, targeting the fundamental cellular energy crisis that accompanies neurodegeneration. By replenishing NAD+ through niacin supplementation, the study aims to support mitochondrial function, enhance cellular repair mechanisms, and potentially slow disease progression.
| Attribute | Value |
|---|---|
| NCT ID | NCT06582706 |
| Phase | Phase 1/2 |
| Status | Recruiting (verified March 2026) |
| Intervention | Extended-Release Niacin (500 mg daily) |
| Control | Placebo (microcrystalline cellulose) |
| Condition | Alzheimer's Disease (mild-moderate) |
| Participants | 30 (estimated) |
| Sponsor | Indiana University |
| Principal Investigator | Jared R. Brosch, MD |
| Collaborator | Alzheimer's Association |
| Location | IU Health Neuroscience Center, Indianapolis, Indiana |
| Design | Randomized, Triple-Blinded, Placebo-Controlled |
| Duration | 60 days |
NAD+ is essential for multiple cellular processes that become impaired in Alzheimer's disease:
Multiple studies have documented NAD+ depletion in AD brain tissue[2]. The decline in cellular NAD+ levels correlates with:
Niacin (nicotinic acid) is one of several NAD+ precursors, along with nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN). Unlike NR and NMN, niacin has been used clinically for decades at high doses for lipid management, establishing a well-characterized safety profile.
Advantages of niacin for AD:
Niacin and NAD+ replenishment have shown promise in multiple preclinical models:
In AD models:
In aging models:
Inclusion criteria:
Exclusion criteria:
| Arm | Intervention | Dose | Duration |
|---|---|---|---|
| Treatment | Extended-Release Niacin | 500 mg daily | 60 days |
| Control | Placebo | Microcrystalline cellulose | 60 days |
Primary Endpoint:
Secondary Endpoint:
The MMSE (Mini-Mental State Examination) score range of 14-24 indicates mild to moderate dementia:
| MMSE Score | Cognitive Status |
|---|---|
| 24-30 | Normal |
| 18-23 | Mild cognitive impairment |
| 12-17 | Moderate cognitive impairment |
| 0-11 | Severe cognitive impairment |
This trial specifically enrolls patients in the mild-to-moderate range, where potential cognitive benefits are most likely to be observed.
Requiring stable cholinesterase inhibitors (donepezil, rivastigmine, galantamine) and/or memantine for 30+ days ensures:
The inclusion of CSF sampling (lumbar puncture) is notable:
Niacin has a well-established safety profile from decades of cardiovascular use:
Common adverse effects:
Less common effects:
The trial includes specific safety exclusions:
Participants will be monitored for:
AD is increasingly recognized as a metabolic disease with fundamental deficits in cellular energy production:
Mitochondrial dysfunction:
NAD+ decline:
Restoring NAD+ levels through niacin supplementation may:
This metabolic approach complements other AD therapeutic strategies that target amyloid, tau, or neuroinflammation directly.
This trial connects to the broader NAD+ replenishment research landscape:
Positive results from this trial could:
Future studies may explore:
NAD+ replenishment may synergize with:
The NCT06582706 trial represents an innovative metabolic approach to Alzheimer's disease treatment. By addressing the fundamental NAD+ depletion that accompanies neurodegeneration, niacin supplementation offers a mechanistically distinct therapeutic strategy.
The trial's strengths include:
Given the limited treatment options for AD and the metabolic basis of neurodegeneration, this trial contributes important evidence for whether NAD+ replenishment can meaningfully impact disease progression.
Nicotinic Acid for the Treatment of Alzheimer's Disease - ClinicalTrials.gov. 2024. ↩︎
Chen X, et al. NAD+ metabolism in Alzheimer's disease brain. Nature Reviews Neurology. 2024. ↩︎
Liu Y, et al. Vitamin B3 and neurodegeneration. Progress in Lipid Research. 2022. ↩︎