Nicotinamide Riboside for Small Fiber Neuropathy

Overseen By Ahmet Hoke, MD, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 2

Sponsor: Johns Hopkins University

Disqualifiers: Diabetes, HIV, Chemotherapy, others

Prior Safety Data This treatment has passed at least one previous human trial

Approved in 2 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 3 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether nicotinamide riboside, a nutritional supplement, can prevent nerve damage and aid nerve healing. Researchers will apply capsaicin, a compound in chili peppers, to the skin to safely induce nerve stress in healthy participants. They will compare the results with a placebo group to determine if the supplement makes a difference. This trial may suit individuals without a history of nerve issues or diseases like diabetes and who pass a simple nerve health check. As a Phase 2 trial, the research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important early-stage findings.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. However, if you have any conditions like diabetes or are undergoing chemotherapy, you may not be eligible to participate.

Is there any evidence suggesting that nicotinamide riboside is likely to be safe for humans?

Research has shown that nicotinamide riboside is generally safe for people. The FDA classifies it as "generally regarded as safe" (GRAS), indicating it is safe to consume. Most individuals taking it have reported only mild side effects, such as an upset stomach, at doses up to 300 mg per day.

In this study, the dose is 900 mg twice a day, which exceeds doses in some other studies. However, researchers have found no major safety concerns with these higher doses. Long-term research has also examined its effects and identified no serious safety issues. This suggests that nicotinamide riboside is well-tolerated by most people. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Most treatments for nerve damage focus on managing symptoms or slowing progression, like using pain relievers or anti-seizure medications. But Nicotinamide Riboside (NR) works differently, targeting nerve health at the cellular level. NR is a form of vitamin B3 that boosts levels of NAD+, a molecule important for energy production and cellular repair. Researchers are excited because this could potentially regenerate nerve fibers and prevent further degeneration, offering hope for actually repairing nerve damage rather than just treating its symptoms.

What evidence suggests that nicotinamide riboside might be an effective treatment for small fiber nerve degeneration?

Research has shown that nicotinamide riboside (NR), which participants in this trial may receive, can boost NAD+ levels in the body. NAD+ plays a crucial role in cell repair and energy production. Studies suggest that NR may help reduce inflammation and support nerve health. Some research indicates that NR might improve muscle strength in conditions like muscular dystrophy. These findings suggest that NR could help prevent nerve damage and aid in nerve repair. ^{2 6 7 8 9}

Who Is on the Research Team?

Ahmet Hoke

Principal Investigator

Johns Hopkins University

Are You a Good Fit for This Trial?

Inclusion Criteria

Neurological examination reveals no impairment.\n

Age: 18-65

You have a body mass index (BMI) of less than 32.

Exclusion Criteria

You have a history of nerve damage, often in the hands or feet.

Any peripheral neuropathy risk factor including diabetes, Vitamin B12 deficiency, HIV-infection, chronic kidney or hepatic disease, hypothyroidism, chemotherapy or other know neurotoxic exposure.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either Nicotinamide Riboside or placebo to evaluate prevention of nerve degeneration and promotion of nerve regeneration

3 months

Bi-weekly visits for monitoring and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotinamide Riboside
• Placebo Oral Tablet

How Is the Trial Designed?

Group I: Nicotinamide Riboside Experimental Treatment 1 Intervention

Experimental group of participants will receive Nicotinamide riboside at a dose of 900 mg twice a day orally.

Group II: Placebo Placebo Group 1 Intervention

Study participants in the placebo arm will receive placebo pills that are similar in size and shape to the experimental group drug.

Nicotinamide Riboside is already approved in United States, European Union for the following indications:

Approved in United States as Niagen for:

• Dietary supplement for general health and wellness

Approved in European Union as Niagen for:

• Dietary supplement for general health and wellness

Who Is Running the Clinical Trial?

Johns Hopkins University

Lead Sponsor

Trials

2,366

Recruited

15,160,000+

Adelson Medical Research Foundation

Collaborator

Trials

1

Recruited

50+

Published Research Related to This Trial

Nicotinamide riboside (NR), a form of vitamin B3, was found to be safe in various toxicity studies, including a 90-day rat study, with no genotoxic effects and no mortality at high doses (5000 mg/kg).

The lowest observed adverse effect level for NR was determined to be 1000 mg/kg/day, indicating that while it is generally safe, higher doses may lead to toxicity in organs such as the liver and kidneys.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety assessment of nicotinamide riboside, a form of vitamin B3. Conze, DB., Crespo-Barreto, J., Kruger, CL.[2019]

Cow milk is a significant source of nicotinamide riboside (NR), containing approximately 12 μmol of NAD(+) precursor vitamins per liter, with NR making up about 40% of this concentration.

The presence of Staphylococcus aureus in milk negatively impacts NR levels, suggesting that controlling this bacteria is crucial for maintaining the nutritional quality of milk.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk. Trammell, SA., Yu, L., Redpath, P., et al.[2023]

Nicotinamide riboside (NR) is a promising NAD+ precursor that has shown potential health benefits in treating various conditions, including cardiovascular, neurodegenerative, and metabolic disorders, based on numerous animal and human studies.

Research indicates that NR may also have therapeutic applications against infections, such as SARS-CoV-2, but challenges related to its bioavailability and safety need to be addressed for effective translation into clinical use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. Mehmel, M., Jovanović, N., Spitz, U.[2021]

Nicotinamide riboside (NR) is a form of vitamin B3 that effectively increases NAD+ levels, which may help counteract age-related declines in this important metabolite.

In a 90-day safety study on Sprague Dawley rats, NR-E showed no significant adverse effects at doses up to 1,200 mg/kg/d, establishing a no-observed-adverse-effect-level (NOAEL) of 500 mg/kg/d for males and 1,200 mg/kg/d for females.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety Assessment of High-Purity, Synthetic Nicotinamide Riboside (NR-E) in a 90-Day Repeated Dose Oral Toxicity Study, With a 28-Day Recovery Arm. Marinescu, AG., Chen, J., Holmes, HE., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7352172/

Nicotinamide Riboside—The Current State of Research and ... Altogether, these findings support that NR could be effective in managing the progression of muscular dystrophy and degeneration, by improving muscular strength ...

2. nature.com nature.com/articles/s41467-024-49092-5

Nicotinamide riboside for peripheral artery disease Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical ...

3. science.org science.org/doi/10.1126/sciadv.adi4862

What is really known about the effects of nicotinamide ... Nicotinamide riboside may play a role in the reduction of inflammatory states and has shown some potential in the treatment of diverse severe diseases.

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9183138/

A Combination of Nicotinamide and D-Ribose (RiaGev) Is ... A Combination of Nicotinamide and D-Ribose (RiaGev) Is Safe and Effective to Increase NAD+ Metabolome in Healthy Middle-Aged Adults: A Randomized, Triple-Blind ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2212877819309160

A reduced form of nicotinamide riboside defines a new ... NRH achieved maximal effects on NAD+ synthesis at approximately 0.5 mM, increasing the intracellular NAD+ levels by more than 10-fold (Figure 1B). The NRH ...

6. fda.gov fda.gov/files/food/published/GRAS-Notice-000635--Nicotinamide-riboside-chloride.pdf

GRAS Notice 635: Nicotinamide riboside chloride The intake of Niagen from the intended uses specified above has been shown to be safe and GRAS based on generally available and accepted ...

7. nature.com nature.com/articles/s41598-019-46120-z

Safety and Metabolism of Long-term Administration ... Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside ... safety data for healthy people taking NR for 8 days.

8. webmd.com webmd.com/vitamins/ai/ingredientmono-1560/nicotinamide-riboside

NICOTINAMIDE RIBOSIDE – Uses, Side Effects, and More When taken by mouth: Nicotinamide riboside chloride is possibly safe when used in doses up to 300 mg daily. Side effects are usually mild and might include ...

9. efsa.onlinelibrary.wiley.com efsa.onlinelibrary.wiley.com/doi/10.2903/j.efsa.2019.5775

Safety of nicotinamide riboside chloride as a novel food ... Animal and human data indicate that the NF contributes to the nicotinamide body pool. There are no concerns regarding genotoxicity. Human ...