Niacin for Alzheimer's Disease

Overseen By Jared R Brosch, MD

Age: 18+

Sex: Any

Trial Phase: Phase 1 & 2

Sponsor: Indiana University

Must be taking: Cholinesterase inhibitors, Memantine

Must not be taking: Antiplatelets, Anticoagulants

Disqualifiers: Severe cerebrovascular disease, Stroke, Liver disease, Renal impairment, others

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: 5

Duration: 8 weeks

30 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether niacin, a form of vitamin B3, can help treat Alzheimer's disease by assessing its penetration into the brain and spinal fluid. Researchers aim to determine if niacin affects levels in the blood and spinal fluid and if it is safe for individuals with Alzheimer's. They seek participants aged 60-85 with mild to moderate Alzheimer's who are on stable medication. Participants must have someone to assist them in following the study rules and must have had a brain scan in the past year. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants a chance to contribute to groundbreaking research.

Will I have to stop taking my current medications?

The trial requires that you stop taking any Vitamin B3 supplements, including niacin, for 4 weeks before joining. However, you must continue taking a stable dose of a cholinesterase inhibitor and/or memantine if you are already on them.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that extended-release niacin is generally safe for use in Alzheimer's disease. Previous studies found that niacin can improve brain function in Alzheimer's patients without major side effects. The FDA has already approved niacin for other uses, indicating a well-understood safety profile.

Although this trial is in the early stages, testing niacin suggests confidence in its safety at the doses used. The trial will specifically examine how well participants handle a 500 mg dose. So far, niacin is considered a safe option for testing in this context. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising for Alzheimer's?

Unlike the standard treatments for Alzheimer's, which typically focus on cholinesterase inhibitors or NMDA receptor antagonists, extended-release niacin is being studied for its potential to improve brain health through a different route. Niacin is thought to enhance blood flow and reduce inflammation, which might help protect brain cells from the damage associated with Alzheimer's. Researchers are excited because if niacin can provide these benefits, it could offer a new way to tackle the disease, potentially slowing its progression with an accessible, well-tolerated vitamin.

What evidence suggests that this treatment might be an effective treatment for Alzheimer's Disease?

This trial will evaluate the effects of Extended Release Niacin on Alzheimer's Disease. Research has shown that increased intake of niacin, a type of vitamin B3, may lower the risk of Alzheimer's Disease and memory problems with age. Studies have found that niacin can improve thinking skills and reduce harmful brain changes linked to Alzheimer's, such as amyloid and tau build-up. Niacin influences brain functions like the body's internal clock and strengthens connections between brain cells. Additionally, niacin has shown potential in boosting overall brain health in various brain disorders. These findings suggest that niacin could benefit people with Alzheimer's Disease. ^{1 2 3 4 6}

Who Is on the Research Team?

Jared Brosch

Principal Investigator

Indiana University

Are You a Good Fit for This Trial?

This trial is for men and women aged 60-85 with mild to moderate Alzheimer's, as shown by a score of 14-24 on the MMSE. Participants must be on a stable dose of Alzheimer's medication or not taking any, have someone who sees them at least three times a week to help with medicine, and recent brain scans.

Inclusion Criteria

I am between 60 and 85 years old.

Neuroimaging (MRI or CT scan of the brain) should be available within 1 year of screening

I have been on a steady dose of memory loss medication for at least 30 days.

Exclusion Criteria

I don't have conditions that make spinal taps unsafe, like bleeding disorders or certain brain masses.

Allergy or sensitivity to B-vitamins or nicotinic acid

I have a severe brain blood vessel condition.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

1 visit (in-person)

Randomization

Participants undergo cognitive and functional assessments, blood work, and CSF collection

1 day

1 visit (in-person)

Treatment

Participants receive 500 mg daily of extended-release niacin or placebo for 60 days

8 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Extended Release Niacin

Trial Overview The study tests if extended-release niacin (vitamin B3) can reach the brain after being taken orally. It compares niacin against a placebo in increasing its levels in blood and spinal fluid, which might show it engages targets in the central nervous system related to Alzheimer's.

How Is the Trial Designed?

Group I: Extended -Release Niacin Experimental Treatment 1 Intervention

500 mg daily

Group II: Placebo Placebo Group 1 Intervention

Microcrystalline cellulose tablets

Extended Release Niacin is already approved in United States for the following indications:

Approved in United States as Niaspan for:

• Primary hyperlipidemia
• Mixed dyslipidemia
• Recurrent nonfatal myocardial infarction in patients with a history of myocardial infarction and hyperlipidemia
• Severe hypertriglyceridemia

Who Is Running the Clinical Trial?

Indiana University

Lead Sponsor

Trials

1,063

Recruited

1,182,000+

Alzheimer's Association

Collaborator

Trials

103

Recruited

44,300+

Published Research Related to This Trial

In a study involving 24 individuals with Alzheimer's disease, a nutraceutical formulation containing various vitamins and compounds helped maintain cognitive performance and behavioral symptoms over 12 months, contrasting with the expected decline seen in placebo groups.

These results support previous findings that such nutraceuticals may improve cognitive function and behavioral symptoms in Alzheimer's patients, suggesting potential benefits of nutritional interventions in managing the disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Maintenance of Cognitive Performance and Mood for Individuals with Alzheimer's Disease Following Consumption of a Nutraceutical Formulation: A One-Year, Open-Label Study. Remington, R., Bechtel, C., Larsen, D., et al.[2017]

A niacin-supplemented diet may serve as a safe and effective non-drug intervention for preventing and treating Alzheimer's disease (AD), as shown in a study involving 18 mice (6 wild-type and 12 AD model mice) over a 6-month period.

The study identified key hub genes (Ctnnb1, Mdm2, Crebbp, Gnb2l1/RACK1, and Pten) and pathways (circadian rhythm, ubiquitin-mediated proteolysis, and long-term potentiation) that suggest niacin enhances cognitive function in AD through multiple biological mechanisms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinic acid supplementation contributes to the amelioration of Alzheimer's disease in mouse models. Wang, Z., Zou, Z., Li, Q.[2022]

Recent studies suggest that combinatorial nutritional formulations, including a Mediterranean-style diet and specific vitamins and supplements, can improve cognitive performance and behavioral issues in Alzheimer's disease.

The review highlights the importance of early, multicomponent nutritional strategies combined with lifestyle changes, indicating that these approaches may modify epigenetic factors related to Alzheimer's, potentially enhancing cognitive function.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nutritional supplementation for Alzheimer's disease? Shea, TB., Remington, R.[2015]

Nutritional supplementation, with or without micronutrient enhancement, did not significantly impact cognitive function or feeding behavior in mild Alzheimer's Disease patients over a 6-month period, indicating no benefits in disease progression.

Both groups showed increased energy consumption and some improvements in nutritional status, but only the group receiving micronutrient enhancement had a significant reduction in serum cholesterol, suggesting potential for further research on this intervention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Micronutrient supplementation in mild Alzheimer disease patients. Planas, M., Conde, M., Audivert, S., et al.[2015]

Extended-release niacin (Niaspan) effectively improves lipid profiles in hyperlipidemic patients, with a maximum dosage of 2,000 mg/day leading to significant reductions in total cholesterol (12.1%), LDL cholesterol (16.7%), triglycerides (34.5%), and lipoprotein(a) (23.6%), while increasing HDL cholesterol by 25.8%.

Flushing was the most common side effect, but it decreased over time; other side effects were minimal and comparable to immediate-release niacin, suggesting that Niaspan is a safe and effective option for lipid modification.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical trial experience with extended-release niacin (Niaspan): dose-escalation study. Goldberg, AC.[2019]

In a 15-week study involving 566 patients with dyslipidaemia, prolonged-release nicotinic acid (niacin) was found to be well tolerated, with flushing being the most common side effect reported in 42% of participants.

The treatment did not lead to serious adverse effects like hepatotoxicity or serious muscle issues, supporting its safety for managing patients with low HDL-cholesterol and elevated cardiovascular risk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of the safety and tolerability of prolonged-release nicotinic acid in a usual care setting: the NAUTILUS study. Vogt, A., Kassner, U., Hostalek, U., et al.[2019]

In a 12-month open-label trial with 14 individuals with early-stage Alzheimer's disease, a vitamin/nutriceutical formulation showed significant improvements in cognitive function as measured by the Dementia Rating Scale and Clock-drawing tests.

Caregivers reported sustained improvements in neuropsychiatric symptoms and daily living activities, suggesting that this formulation may be a promising treatment option for early-stage Alzheimer's, potentially serving as a supplement to traditional medications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy of a vitamin/nutriceutical formulation for early-stage Alzheimer's disease: a 1-year, open-label pilot study with an 16-month caregiver extension. Chan, A., Paskavitz, J., Remington, R., et al.[2022]

In a randomized controlled trial involving 77 patients with mild to moderate Alzheimer's disease, a daily micronutrient supplement (including fish oil, carotenoids, and vitamin E) for 12 months led to significant improvements in blood and skin carotenoid levels, omega-3 fatty acids, and vitamin E concentrations.

The active treatment group showed notable enhancements in memory and mood, with a significant difference in clinical assessments of memory compared to the placebo group, suggesting that this micronutrient supplementation could be beneficial in managing Alzheimer's disease symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Supplementation With Carotenoids, Omega-3 Fatty Acids, and Vitamin E Has a Positive Effect on the Symptoms and Progression of Alzheimer's Disease. Nolan, JM., Power, R., Howard, AN., et al.[2022]

Nicotinamide-loaded solid lipid nanoparticles (SLNs) functionalized with phosphatidylserine (PS) showed improved brain delivery and safety, making them a promising option for treating Alzheimer's disease.

In a rat model, PS-functionalized SLNs significantly enhanced cognitive function and preserved neuronal cells better than traditional oral nicotinamide administration, indicating their potential effectiveness in early Alzheimer's treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide loaded functionalized solid lipid nanoparticles improves cognition in Alzheimer's disease animal model by reducing Tau hyperphosphorylation. Vakilinezhad, MA., Amini, A., Akbari Javar, H., et al.[2020]

In a study of 32 patients with type 2 diabetes, Niaspan significantly increased HDL cholesterol by 34% and reduced triglycerides by 36%, indicating its effectiveness in improving lipid profiles.

Niaspan also led to a significant decrease in hemoglobin A1c levels by 0.5%, suggesting it can help with glycemic control without worsening blood sugar levels, and it was generally safe with no significant changes in liver enzymes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cholesterol and glycemic effects of Niaspan in patients with type 2 diabetes. Kane, MP., Hamilton, RA., Addesse, E., et al.[2019]

Extended-release niacin/laropiprant (ERN/LRPT) demonstrated a favorable safety profile, with fewer flushing-related side effects compared to traditional niacin (ERN-NSP), based on data from 4747 participants across multiple studies lasting up to 52 weeks.

While there were slight increases in liver enzymes with ERN/LRPT, these were reversible and not linked to liver damage, indicating that ERN/LRPT can be safely used to enhance the lipid-modifying effects of niacin without significant adverse effects on muscle or liver health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of extended-release niacin/laropiprant in patients with dyslipidemia. McKenney, J., Bays, H., Koren, M., et al.[2015]

Niaspan, an extended-release form of Niacin, significantly reduced brain damage and improved recovery in rats after a stroke, showing its potential as a neuroprotective treatment when administered shortly after the event.

The neuroprotective effects of Niaspan were linked to decreased cell death and inflammation, as evidenced by lower levels of apoptosis markers and inflammatory cytokines, along with increased expression of growth factors and signaling pathways that promote brain health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niaspan treatment induces neuroprotection after stroke. Shehadah, A., Chen, J., Zacharek, A., et al.[2021]

In a study of 82 dyslipidemic patients treated with niacin, 83% tolerated the treatment well, achieving beneficial effects on high-density lipoprotein cholesterol (HDL-C) levels, indicating niacin's efficacy as a lipid-modifying drug.

However, sustained-release niacin was associated with a higher risk of hepatitis, particularly in patients with diabetes, suggesting that its use should be closely monitored, and its availability as a nonprescription drug should be reconsidered.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Niacin revisited: clinical observations on an important but underutilized drug. Henkin, Y., Oberman, A., Hurst, DC., et al.[2019]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06582706

Nicotinic Acid for the Treatment of Alzheimer's Disease Overall data support that niacin can be beneficial at mid/late AD stages limiting both amyloid and tau pathologies. Niacin formulations are currently being ...

2. withpower.com withpower.com/trial/niacin-for-alzheimers-disease-33a5a

Niacin for Alzheimer's Disease Increased dietary intake of niacin is correlated with reduced risk of Alzheimer's Disease and age-associated cognitive decline. The goal of this study is to ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9622504/

Nicotinic acid supplementation contributes to the amelioration ... Our research also found that niacin can improve AD cognitive ability through circadian rhythm, ubiquitin-mediated proteolysis, and long-term potentiation.

4. sciencedirect.com sciencedirect.com/science/article/pii/S1878747923019104

The Promise of Niacin in Neurology Recent evidence has posited niacin as a promising therapeutic for several neurological disorders. In this review, we discuss the biochemistry of niacin.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10420858/

Association between dietary niacin intake and cognitive ... A clinical study suggests that niacin supplementation has beneficial effects on cognitive function in later life (Ma et al., 2016).

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC1739176/

Dietary niacin and the risk of incident Alzheimer's disease ... We examined whether dietary intake of niacin was associated with incident Alzheimer's disease (AD) and cognitive decline in a large, prospective study.