Nicotinamide Riboside for Stroke

Overseen By Dianna M Milewicz, MD, PhD

Age: Any Age

Sex: Any

Trial Phase: Phase 1

Sponsor: The University of Texas Health Science Center, Houston

Disqualifiers: Aortic surgery, Niacin allergy, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 8-12 weeks

15 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether a supplement called Nicotinamide Riboside (NR) can benefit people with SMDS, a rare condition caused by a specific gene mutation affecting the aorta. Researchers aim to determine if NR can reduce glucose uptake in the aorta and alter blood levels of certain molecules, while ensuring patient safety. Suitable candidates for this trial include those with SMDS and a confirmed ACTA2 mutation affecting their aorta, who have not recently taken NR or niacin supplements. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new treatment.

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, it does mention that you cannot participate if you are in another intervention trial, which might imply some restrictions on other treatments.

Is there any evidence suggesting that Nicotinamide Riboside is likely to be safe for humans?

Research shows that nicotinamide riboside (NR), a type of vitamin B3, is generally safe for people. Studies indicate that NR is well-tolerated and helps increase NAD+ levels in the body. NAD+ is a molecule that supports proper cell function.

NR has received GRAS status, meaning "generally regarded as safe," indicating experts consider it safe for use in foods and supplements. In human trials, NR did not cause serious side effects, even at higher doses.

Animal studies showed some effects at very high doses, but these doses were much larger than what humans would normally take. Overall, NR appears to be a safe choice for improving health. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Nicotinamide Riboside (NR) is unique because it offers a novel approach to stroke treatment by targeting cellular energy production. While most standard treatments for stroke, like thrombolytics and antiplatelet drugs, focus on restoring blood flow or preventing blood clots, NR works by enhancing mitochondrial function and cellular repair. Researchers are excited about NR because it has the potential to protect brain cells from damage during a stroke and promote recovery by boosting the natural energy processes within cells. This mechanism of action sets it apart from existing treatments and could offer a new avenue for improving outcomes in stroke patients.

What evidence suggests that Nicotinamide Riboside might be an effective treatment for stroke?

Research suggests that nicotinamide riboside (NR), which participants in this trial will receive, might aid in stroke recovery. In one study, mice given nicotinamide showed less brain damage and improved brain structure after a stroke. NR, a form of vitamin B3, helps increase NAD+ levels in the body, which is crucial for energy and cell repair. Although NR is generally considered safe for humans, further research is needed to confirm its effectiveness in stroke patients. Early results indicate potential benefits, but clinical trials are essential to gain more understanding. ^{6 7 8 9 10}

Who Is on the Research Team?

Dianna Milewicz, MD, PhD

Principal Investigator

The University of Texas Health Science Center, Houston

Are You a Good Fit for This Trial?

This trial is for individuals with Smooth Muscle Dysfunction Syndrome (SMDS) and a specific ACTA2 gene mutation. They must have their native ascending aorta, weigh at least 12 kg, and not be pregnant. Participants agree to use contraception during the study and haven't taken niacin or NR supplements recently.

Inclusion Criteria

Must agree to use acceptable method of contraception, including abstinence, a barrier method (diaphragm or condom), Depo-Provera, or an oral contraceptive, for the duration of the study

My ascending aorta has not been surgically replaced.

My SMDS is caused by a specific ACTA2 mutation.

Exclusion Criteria

Known allergy or sensitivity to niacin or nicotinamide riboside

Failure to provide informed consent

Concurrent participation in another intervention trial

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Nicotinamide Riboside (NR) to evaluate its effects on glucose uptake in the aorta, blood NAD+ and NR levels, and aortic measurements

8-12 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Nicotinamide Riboside (NR)

Trial Overview The trial tests if Nicotinamide Riboside (NR) can reduce glucose uptake in the aorta of SMDS patients, alter blood NAD+ and NR levels, maintain stable aortic measurements after treatment, and assesses its safety and tolerability.

How Is the Trial Designed?

Group I: Treatment Experimental Treatment 1 Intervention

Nicotinamide Riboside (NR) is already approved in United States, European Union, Canada, Brazil for the following indications:

Approved in United States as Niagen for:

• General health supplement
• Alzheimer's Disease (Phase 1)
• Parkinson's Disease (Phase 2)
• Mild Cognitive Impairment (Phase 1/2)

Approved in European Union as Niagen for:

• Novel food for use in supplements, foods for special medical purposes, total diet replacement for weight control, and meal replacements for the adult population

Approved in Canada as Niagen for:

• Natural health product

Approved in Brazil as Niagen for:

• Use in medical foods

Who Is Running the Clinical Trial?

The University of Texas Health Science Center, Houston

Lead Sponsor

Trials

974

Recruited

361,000+

Published Research Related to This Trial

Long-term supplementation of nicotinamide riboside (NR) over 2 years in individuals with ataxia telangiectasia (A-T) was found to be safe and well tolerated, with most participants experiencing no adverse effects.

The study showed significant improvements in neuromotor function, particularly in coordination and eye movements, with a slower progression of symptoms compared to historical data, indicating potential therapeutic benefits of NR in managing A-T.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Nicotinamide Riboside Use Improves Coordination and Eye Movements in Ataxia Telangiectasia. Presterud, R., Deng, WH., Wennerström, AB., 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]

In an 8-week clinical trial with overweight but healthy participants, nicotinamide riboside (NR) significantly increased whole blood NAD+ levels in a dose-dependent manner, with increases of 22%, 51%, and 142% for doses of 100, 300, and 1000 mg, respectively.

The study found NR to be safe, with no significant adverse effects reported compared to placebo, and it did not negatively impact cholesterol levels or 1-carbon metabolism, supporting its potential as a dietary supplement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and Metabolism of Long-term Administration of NIAGEN (Nicotinamide Riboside Chloride) in a Randomized, Double-Blind, Placebo-controlled Clinical Trial of Healthy Overweight Adults. Conze, D., Brenner, C., Kruger, CL.[2023]

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]

Nicotinamide phosphoribosyltransferase (NAMPT) plays a crucial role in producing NAD, which is important for protecting brain cells during a stroke, making it a promising target for new stroke therapies.

The review discusses five strategies to enhance NAMPT's effects, including overexpression, recombinant forms, and its products like nicotinamide mononucleotide (NMN), highlighting their potential to improve treatment for both ischaemic and haemorrhagic strokes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeting NAMPT as a therapeutic strategy against stroke. Wang, SN., Miao, CY.[2021]

Nicotinamide riboside, a precursor to NAD and a form of Vitamin B3, has been shown to enhance insulin sensitivity, promote mitochondrial biogenesis, and support brain health, particularly in models of Alzheimer's disease.

It is metabolized through two pathways, one that produces nicotinamide and another involving specific kinases that help raise NAD levels in tissues, suggesting its unique health benefits may be linked to these metabolic processes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection. Chi, Y., Sauve, AA.[2021]

1-methylnicotinamide (MNA) demonstrated significant anti-thrombotic activity in various rat models, showing a dose-dependent thrombolytic response and reduced arterial thrombosis, suggesting it could be a potential therapeutic agent for thrombotic conditions.

The mechanism of MNA's action involves the enhancement of prostacyclin production through cyclooxygenase-2, indicating its role in regulating thrombotic and inflammatory processes in the cardiovascular system.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

1-Methylnicotinamide (MNA), a primary metabolite of nicotinamide, exerts anti-thrombotic activity mediated by a cyclooxygenase-2/prostacyclin pathway. Chlopicki, S., Swies, J., Mogielnicki, A., et al.[2018]

Nicotinamide mononucleotides (NMN) significantly improved neurological function and reduced brain edema in a mouse model of cerebral infarction, indicating potential protective effects against brain damage.

While NMN treatment positively influenced inflammation, apoptosis, and overall health in the mice, it did not significantly affect hemorrhage or hematoma volumes, suggesting its benefits may be more focused on tissue protection rather than directly reducing bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mechanisms of transformation of nicotinamide mononucleotides to cerebral infarction hemorrhage based on MCAO model. Shu, L., Shen, X., Zhao, Y., et al.[2022]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5471593/

Nicotinamide Administration Improves Remyelination after ... Results. The nicotinamide-treated mice showed significantly lower infarct area 7 d after stroke induction and significantly higher fractional anisotropy (FA) ...

2. mdpi.com mdpi.com/1467-3045/47/6/400

Niacin and Stroke: The Role of Supplementation ... Niacin therapy has been a mainstay in traditional secondary prevention of stroke. Supplemental use of niacin has been used to improve lipid panel markers.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT04809974

Study Details | NCT04809974 | Clinical Trial of Niagen to ... The study will assess whether Niagen, a safe dietary supplement, improves recovery of COVID-19 related symptoms in individuals who were infected at least 2 ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0022356524343101

NAD+ and Vitamin B3: From Metabolism to Therapies This review considers current knowledge of NAD + metabolism in humans and microbes, including new insights into mechanisms that regulate NAD + biosynthetic ...

5. withpower.com withpower.com/trial/phase-1-cerebrovascular-disorders-2-2024-63cc8

Nicotinamide Riboside for Stroke Nicotinamide Riboside (NR) has been studied in humans and is generally recognized as safe, with no significant differences in adverse events compared to a ...

6. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/26791540/

Safety assessment of nicotinamide riboside, a form ... Target organs of toxicity were liver, kidney, ovaries, and testes. The lowest observed adverse effect level for NR was 1000 mg/kg/day, and the no observed ...

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

Nicotinamide Riboside—The Current State of Research and ... NR chloride has been given GRAS status (generally regarded as safe) which further supports its rapid implementation as a drug-like therapy. However, to adapt NR ...

8. rally.massgeneralbrigham.org rally.massgeneralbrigham.org/study/vitamin_b3_brain_imaging

Brain imaging study of a Vitamin B3 dietary supplement We are interested in seeing if and how a dietary supplement for Vitamin B3 called Nicotinamide Riboside (NR) causes an improvement in brain energy metabolism.

9. researchgate.net researchgate.net/publication/334256296_Safety_and_Metabolism_of_Long-term_Administration_of_NIAGEN_Nicotinamide_Riboside_Chloride_in_a_Randomized_Double-Blind_Placebo-controlled_Clinical_Trial_of_Healthy_Overweight_Adults

(PDF) Safety and Metabolism of Long-term Administration ... A crystal form of NR chloride termed NIAGEN is generally recognized as safe (GRAS) for use in foods and the subject of two New Dietary Ingredient Notifications ...

10. clinicaltrials.gov clinicaltrials.gov/study/NCT04691986

Impacts of Nicotinamide Riboside on Functional Capacity ... Human trials have demonstrated that nicotinamide riboside (NR), a form of vitamin B3, is safe and effectively increases NAD+ levels. In animal studies, NR ...