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

Trial Summary

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.

What data supports the effectiveness of the treatment Extended Release Niacin, Niaspan, Nicotinic Acid, Vitamin B3 for Alzheimer's Disease?

Research on similar nutritional formulations, which include vitamins and other nutrients, shows that they can help maintain cognitive performance and improve behavioral symptoms in people with Alzheimer's disease. Although these studies did not specifically test niacin, they suggest that combining vitamins and nutrients might be beneficial for Alzheimer's patients. ^{1 2 3 4 5}

Is niacin safe for humans?

Niacin, also known as Vitamin B3, has been studied for safety in various forms, including extended-release versions like Niaspan. It is generally considered safe for humans, but some studies have focused on its use for conditions like cholesterol management and diabetes, where it has been well-tolerated. However, as with any treatment, there may be side effects, so it's important to discuss with a healthcare provider. ^{6 7 8 9 10}

How does the drug Niaspan differ from other Alzheimer's treatments?

Niaspan, an extended-release form of niacin (vitamin B3), is unique because it is primarily used to improve cholesterol levels and prevent cardiovascular diseases, but it may also offer neuroprotective benefits and help in Alzheimer's by potentially reducing harmful protein build-up in the brain. Unlike other Alzheimer's treatments, it is taken once a day, which can improve patient compliance. ^{6 7 11 12 13}

What is the purpose of this trial?

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 collect data on the penetration of commercially available, FDA approved, extended-release niacin into the spinal fluid. One dose of 500 mg nicotinic acid will be used (in addition to placebo) to build a dose response curve for this compound in human cerebrospinal fluid. This objective will demonstrate target engagement of HCAR2 in the central nervous system, after oral treatment with niacin. The primary endpoints are to show increased nicotinic acid levels in blood and cerebrospinal fluid. A secondary endpoint is to collect safety and tolerability data of niacin in this particular population.

Research Team

Jared Brosch

Principal Investigator

Indiana University

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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 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]

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]

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]

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]

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]

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]

References

1. United States 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. [2022]

2. Netherlands 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. [2017]

3. United States pubmed.ncbi.nlm.nih.gov

Nutritional supplementation for Alzheimer's disease? [2015]

4. England pubmed.ncbi.nlm.nih.gov

Micronutrient supplementation in mild Alzheimer disease patients. [2015]

5. Netherlands 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. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Niaspan treatment induces neuroprotection after stroke. [2021]

7. England pubmed.ncbi.nlm.nih.gov

Evaluation of the safety and tolerability of prolonged-release nicotinic acid in a usual care setting: the NAUTILUS study. [2019]

8. United States pubmed.ncbi.nlm.nih.gov

Cholesterol and glycemic effects of Niaspan in patients with type 2 diabetes. [2019]

9. United States pubmed.ncbi.nlm.nih.gov

Niacin revisited: clinical observations on an important but underutilized drug. [2019]

10. United States pubmed.ncbi.nlm.nih.gov

Safety of extended-release niacin/laropiprant in patients with dyslipidemia. [2015]

11. Switzerland pubmed.ncbi.nlm.nih.gov

Nicotinamide loaded functionalized solid lipid nanoparticles improves cognition in Alzheimer's disease animal model by reducing Tau hyperphosphorylation. [2020]

12. China pubmed.ncbi.nlm.nih.gov

Nicotinic acid supplementation contributes to the amelioration of Alzheimer's disease in mouse models. [2022]

13. United States pubmed.ncbi.nlm.nih.gov

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