Nicotinamide Riboside for Cognitive Impairment and Sleep Quality

Recruiting at 2 trial locations

Overseen By Carleara Weiss, PhD, MS, RN

Age: 65+

Sex: Any

Trial Phase: Academic

Sponsor: State University of New York at Buffalo

Disqualifiers: Dementia

Compensation: Varies

Number of Visits: Unknown

Duration: 12 weeks

50 Participants Needed

Trial Summary

What is the purpose of this trial?

Poor sleep quality and short sleep duration may be a mechanistic component of cognitive impairment in older adults, associated with a decline in brain-derived neurotrophic factor. Increasing the availability of nicotinamide adenine dinucleotide (NAD+) with supplementation of its precursor, nicotinamide riboside (NR), a form of vitamin B3 may increase the expression of brain-derived neurotrophic factor. This study proposes to examine the benefits of NR supplementation on sleep and cognitive function in older adults with comprehensive subjective and objective measures and to explore its impacts on serum brain-derived neurotrophic factor.

Do I need to stop my current medications for this trial?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the drug Nicotinamide Riboside for cognitive impairment and sleep quality?

Research shows that Nicotinamide Riboside (NR) can increase NAD+ levels, which are important for energy metabolism, and improve brain function in some animal models. Additionally, a study found that NR improved short-term memory in aged mice and reduced drowsiness in older adults, suggesting potential benefits for cognitive function and sleep quality. ^{1 2 3 4 5}

Is nicotinamide riboside safe for humans?

Nicotinamide riboside (NR) has been shown to be generally safe in humans, with studies reporting no significant differences in adverse events between NR and placebo groups. It is recognized as safe for use in foods and supplements, and no serious side effects were observed in trials with different doses. ^{1 2 3 6 7}

How does the drug nicotinamide riboside differ from other treatments for cognitive impairment and sleep quality?

Nicotinamide riboside is unique because it increases NAD+ levels in the body, which is important for energy metabolism and brain function, potentially improving cognitive impairment and sleep quality. Unlike other treatments, it is a precursor to NAD+ and has shown promise in both animal and human studies for various conditions, including neurodegenerative disorders. ^{1 2 3 4 8}

Eligibility Criteria

This trial is for older adults who have trouble sleeping and may be experiencing some cognitive challenges. To join, they need to score more than 5 on a sleep quality test but can't have dementia as indicated by scoring less than 20 on a mental status questionnaire.

Inclusion Criteria

Sleep Quality. Pittsburgh Sleep Quality Index (PSQI) global score >5

Exclusion Criteria

Dementia. Veteran Affairs - St. Louis University Mental Status questionnaire (VA-SLUMS) score <20

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 500mg of nicotinamide riboside or placebo twice daily

12 weeks

Regular visits for assessment

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Nicotinamide Riboside
• Placebo

Trial Overview The study is testing whether taking Nicotinamide Riboside (NR), a vitamin B3 form, improves sleep and brain function in older adults. Participants will either receive NR or a placebo without active ingredients to compare the effects.

Participant Groups

Group I: Intervention Experimental Treatment 1 Intervention

Participants in the intervention group will receive 500mg of NR twice daily

Group II: Placebo Placebo Group 1 Intervention

Participants in the intervention group will receive 500mg of sham placebo twice daily

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?

State University of New York at Buffalo

Lead Sponsor

Trials

279

Recruited

52,600+

Findings from Research

Nicotinamide riboside (NR) was safely administered to 20 older adults with mild cognitive impairment (MCI) over a 10-week period, resulting in a significant 2.6-fold increase in blood NAD+ levels without any adverse effects reported between the NR and placebo groups.

While NR treatment did not improve cognitive function as measured by the Montreal Cognitive Assessment (MoCA), it did lead to a reduction in cerebral blood flow in specific brain regions, indicating that further research is needed to explore its potential effects on cognition and brain health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment. Orr, ME., Kotkowski, E., Ramirez, P., et al.[2023]

A study involving 108 older adults showed that taking nicotinamide mononucleotide (NMN) in the afternoon significantly improved lower limb function and reduced drowsiness after 12 weeks.

The NMN group demonstrated the largest improvements in physical performance, particularly in the 5-times sit-to-stand test, indicating its potential to enhance physical capabilities and combat fatigue in older adults.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study. Kim, M., Seol, J., Sato, T., et al.[2022]

Oral supplementation with nicotinamide riboside has shown potential in improving learning and memory while reducing Alzheimer's disease-related pathology in mouse models, indicating its efficacy in combating age-related cognitive decline.

Nicotinamide riboside is well tolerated in humans with minimal side effects, suggesting it could be a safe therapeutic option for enhancing cognitive function and maintaining brain health as we age.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Can nicotinamide riboside protect against cognitive impairment? Braidy, N., Liu, Y.[2021]

Nicotinamide ribose (NR) supplementation for 3 months improved cognitive functions, such as short-term spatial memory in aged mice and contextual fear memory in Alzheimer's disease (AD) model mice, indicating its potential efficacy in combating cognitive decline.

NR supplementation also reduced harmful effects associated with AD, such as the accumulation of amyloid-beta (Aβ) and the activation of astrocytes, suggesting a mechanism of action that may help prevent the progression of dementia.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Nicotinamide ribose ameliorates cognitive impairment of aged and Alzheimer's disease model mice. Xie, X., Gao, Y., Zeng, M., et al.[2022]

A 7-day supplementation with RiaGev, a combination of nicotinamide and D-ribose, significantly increased NAD+ levels in healthy middle-aged adults, particularly boosting NADP+ by 27% compared to placebo, indicating its efficacy in enhancing the NAD metabolome.

Participants taking RiaGev reported reduced fatigue and improved mental concentration, with no significant adverse effects observed, suggesting that it is a safe option for enhancing energy metabolism and overall well-being.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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, Placebo-Controlled, Cross-Over Pilot Clinical Trial. Xue, Y., Shamp, T., Nagana Gowda, GA., et al.[2022]

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 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]

References

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

A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Effect of 12-Week Intake of Nicotinamide Mononucleotide on Sleep Quality, Fatigue, and Physical Performance in Older Japanese Adults: A Randomized, Double-Blind Placebo-Controlled Study. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Can nicotinamide riboside protect against cognitive impairment? [2021]

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

Nicotinamide ribose ameliorates cognitive impairment of aged and Alzheimer's disease model mice. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

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, Placebo-Controlled, Cross-Over Pilot Clinical Trial. [2022]

6. 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]

7. 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]

8. Switzerland pubmed.ncbi.nlm.nih.gov

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