Nicotinamide Riboside for Stroke

Overseen By Dianna Milewicz, MD, PhD

Age: < 65

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

5 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the drug Nicotinamide Riboside for stroke?

Research shows that Nicotinamide Riboside (NR) can increase NAD+ levels in the body, which is important for many body functions. Studies suggest that boosting NAD+ might help protect the brain during a stroke, as similar compounds have shown neuroprotective effects in stroke models. ^{1 2 3 4 5}

Is Nicotinamide Riboside (NR) safe for human use?

Nicotinamide Riboside (NR) has been studied in humans and is generally recognized as safe, with no significant differences in adverse events compared to a placebo in clinical trials. It has been tested at various doses and shown to be well-tolerated, with no serious side effects reported. ^{1 3 6 7 8}

How is the drug Nicotinamide Riboside unique for treating stroke?

Nicotinamide Riboside (NR) is unique because it is a form of Vitamin B3 that boosts levels of NAD+ (a vital molecule for energy and cell repair) in the body, which may help in treating various conditions, including stroke. Unlike traditional stroke treatments, NR is a dietary supplement that has shown potential benefits in cardiovascular and neurodegenerative disorders by enhancing metabolism and neuroprotection. ^{1 3 6 9 10}

What is the purpose of this trial?

The purpose of this study is to determine whether SMDS patients treated with NR at the proposed dose exhibit decreased glucose uptake in the aorta, to determine if NR treatment results in measurable changes of blood NAD+ and NR levels, to determine if aortic measurements are stable after treatment with NR and to evaluate the safety and tolerability of NR in SMDS patients.

Research Team

David Murdock, MD

Principal Investigator

The University of Texas Health Science Center, Houston

Eligibility Criteria

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

My ascending aorta has not been surgically replaced.

My SMDS is caused by a specific ACTA2 mutation.

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

Exclusion Criteria

Known allergy or sensitivity to niacin or nicotinamide riboside

Failure to provide informed consent

Concurrent participation in another intervention trial

Timeline

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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]

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]

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]

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 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]

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, 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]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. [2021]

2. England pubmed.ncbi.nlm.nih.gov

Targeting NAMPT as a therapeutic strategy against stroke. [2021]

3. England 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. [2023]

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

1-Methylnicotinamide (MNA), a primary metabolite of nicotinamide, exerts anti-thrombotic activity mediated by a cyclooxygenase-2/prostacyclin pathway. [2018]

5. Saudi Arabia pubmed.ncbi.nlm.nih.gov

Mechanisms of transformation of nicotinamide mononucleotides to cerebral infarction hemorrhage based on MCAO model. [2022]

6. England pubmed.ncbi.nlm.nih.gov

Safety assessment of nicotinamide riboside, a form of vitamin B3. [2019]

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

Long-Term Nicotinamide Riboside Use Improves Coordination and Eye Movements in Ataxia Telangiectasia. [2023]

8. United States 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. [2021]

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

Nicotinamide Riboside Is a Major NAD+ Precursor Vitamin in Cow Milk. [2023]

10. England pubmed.ncbi.nlm.nih.gov

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