Nicotinamide Riboside for Alzheimer's Disease
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase < 1
Recruiting
Sponsor: Mclean Hospital
Must not be taking: Benzodiazepines, Barbiturates, Opiates, others
Disqualifiers: Psychotic disorder, Stroke, Cancer, others
No Placebo Group
Approved in 2 Jurisdictions
Trial Summary
What is the purpose of this trial?This trial is testing nicotinamide riboside (NR), a form of vitamin B3, to see if it can help people with early memory problems or mild Alzheimer's. The idea is that NR can boost a molecule called NAD+ in the brain, which helps cells produce energy and reduces stress. Researchers hope this will improve brain function in these patients. Nicotinamide riboside (NR) is a precursor to NAD+ and has shown potential in improving learning and memory in animal models of dementia.
Will I have to stop taking my current medications?
You may need to stop taking certain medications before joining the trial. If you are taking niacin (or a vitamin supplement with niacin) over 200mg, you must stop for two weeks before starting. Also, you cannot use medications that affect cognition or certain supplements like mitochondrial enhancers.
What data supports the effectiveness of the drug Nicotinamide Riboside for Alzheimer's Disease?
Research shows that Nicotinamide Riboside (NR) can increase levels of NAD+ in the body, which is important for energy metabolism and brain function. In studies with mice, NR improved memory and reduced Alzheimer's-related brain changes. Additionally, a small human study found NR to be safe and increased NAD+ levels, suggesting potential benefits for brain health.
12345Is nicotinamide riboside safe for human use?
Nicotinamide riboside (NR), a form of vitamin B3, has been studied for safety in both animals and humans. In human trials, NR was generally well-tolerated with no significant adverse effects reported, even at higher doses. Animal studies also showed no severe toxicity, although some effects on organs were noted at very high doses.
26789How is the treatment nicotinamide riboside unique for Alzheimer's disease?
Nicotinamide riboside is unique because it is a form of Vitamin B3 that boosts levels of NAD+ (a molecule important for energy and cell health), which may help protect against age-related cognitive decline, unlike traditional Alzheimer's treatments that often focus on symptom management.
167910Eligibility Criteria
This trial is for individuals aged 55-89 with mild cognitive impairment or mild Alzheimer's dementia, who can understand study risks and consent. They must speak English fluently, have a study partner, carry the APOE ε4 allele or show positive AD biomarkers. Exclusions include serious medical conditions affecting cognition, recent mood disorders, psychotic history, MRI contraindications, NR intolerance, recent strokes or substance abuse.Inclusion Criteria
Ability to speak and read fluently in English
My hearing and vision are normal or corrected to normal.
I understand the study's risks and goals, and I can sign the consent form.
+2 more
Exclusion Criteria
I am currently taking supplements to boost my mitochondria or antioxidants.
I have taken L-DOPA, anti-Parkinsonian drugs, or anti-amyloid treatments.
MRI safety contraindications
+16 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants take 4 pills daily, each containing 250 mg NR, for 12 weeks
12 weeks
Baseline, 6 and 12 weeks (in-person)
Follow-up
Participants are monitored for changes in mood, brain redox state, NAD+ levels, functional status, mitochondrial function, antioxidant levels, behavioral symptoms, spirituality, and cognitive status
4 weeks
Participant Groups
The trial tests whether Nicotinamide Riboside (NR) improves brain energy metabolism and reduces oxidative stress in patients with mild cognitive impairment or Alzheimer's dementia. It aims to see if NR can enhance cognitive function by supplementing the body's energy molecules.
1Treatment groups
Experimental Treatment
Group I: Mild Cognitive Impairment and Alzheimer's DementiaExperimental Treatment1 Intervention
Participants will take 4 pills every day, each containing 250 mg NR (NIAGEN® by Chromadex; www.chromadex.com), via the oral route, for 12 weeks.
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 Tru Niagen for:
- Dietary supplement for general health and wellness
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
McLean HospitalBelmont, MA
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Who Is Running the Clinical Trial?
Mclean HospitalLead Sponsor
National Institute on Aging (NIA)Collaborator
References
Can nicotinamide riboside protect against cognitive impairment? [2021]The present review aims to address the clinical benefits of using nicotinamide riboside, a precursor to the essential pyridine nucleotide, nicotinamide adenine dinucleotide (NAD+) as a therapeutic agent to attenuate age-related cognitive decline.
A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment. [2023]Nicotinamide riboside (NR) increases blood levels of NAD+, a cofactor central to energy metabolism, and improves brain function in some rodent models of neurodegeneration. We conducted a placebo-controlled randomized pilot study with the primary objective of determining safety of NR in older adults with mild cognitive impairment (MCI). Twenty subjects with MCI were randomized to receive placebo or NR using dose escalation to achieve, and maintain, a final dose of 1 g/day over a 10-week study duration. The primary outcome was post-treatment change from baseline measures of cognition (Montreal Cognitive Assessment, MoCA). Predefined secondary outcomes included post-treatment changes in cerebral blood flow (CBF); blood NAD+ levels; and additional neurocognitive, psychometric, and physical performance tests. DNA methylation was assessed in peripheral blood mononuclear cells (PBMCs) as an exploratory outcome. The target NR dose was safely achieved as evidenced by a 2.6-fold increase in blood NAD+ in the NR group (p
Long-Term Nicotinamide Riboside Use Improves Coordination and Eye Movements in Ataxia Telangiectasia. [2023]Supplementation of nicotinamide riboside (NR) ameliorates neuropathology in animal models of ataxia telangiectasia (A-T). In humans, short-term NR supplementation showed benefits in neurological outcome.
Nicotinamide loaded functionalized solid lipid nanoparticles improves cognition in Alzheimer's disease animal model by reducing Tau hyperphosphorylation. [2020]Nicotinamide is considered to be effective in halting the Alzheimer's disease progression. The body could absorb a limited amount of nicotinamide at a time, requiring multiple doses through a day. To overcome such an obstacle which reduces the patient compliance, a sustained/controlled delivery system could be useful.
Nicotinamide ribose ameliorates cognitive impairment of aged and Alzheimer's disease model mice. [2022]Nicotinamide adenine dinucleotide (NAD) supplementation to repair the disabled mitochondria is a promising strategy for the treatment of Alzheimer's disease (AD) and other dementia. Nicotinamide ribose (NR) is a safe NAD precursor with high oral bioavailability, and has beneficial effects on aging. Here, we applied NR supplied food (2.5 g/kg food) to APP/PS1 transgenic AD model mice and aged mice for 3 months. Cognitive function, locomotor activity and anxiety level were assessed by standard behavioral tests. The change of body weight, the activation of microglia and astrocytes, the accumulation of Aβ and the level of serum nicotinamide phosphoribosyltransferase (NAMPT) were determined for the evaluation of pathological processes. We found that NR supplementation improved the short-term spatial memory of aged mice, and the contextual fear memory of AD mice. Moreover, NR supplementation inhibited the activation of astrocytes and the elevation of serum NAMPT of aged mice. For AD model mice, NR supplementation inhibited the accumulation of Aβ and the migration of astrocyte to Aβ. In addition, NR supplementation inhibit the body weight gain of aged and APP/PS1 mice. Thus, NR has selective benefits for both AD and aged mice, and the oral uptake of NR can be used to prevent the progression of dementia.
Safety assessment of nicotinamide riboside, a form of vitamin B3. [2019]Nicotinamide riboside (NR) is a naturally occurring form of vitamin B3 present in trace amounts in some foods. Like niacin, it has been shown to be a precursor in the biosynthesis of nicotinamide adenine dinucleotide (NAD+). The safety of Niagen™, a synthetic form of NR, was determined using a bacterial reverse mutagenesis assay (Ames), an in vitro chromosome aberration assay, an in vivo micronucleus assay, and acute, 14-day and 90-day rat toxicology studies. NR was not genotoxic. There was no mortality at an oral dose of 5000 mg/kg. Based on the results of a 14-day study, a 90-day study was performed comparing NR at 300, 1000, and 3000 mg/kg/day to an equimolar dose of nicotinamide at 1260 mg/kg/day as a positive control. Results from the study show that NR had a similar toxicity profile to nicotinamide at the highest dose tested. 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 adverse effect level was 300 mg/kg/day.
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]Nicotinamide riboside (NR) is a newly discovered nicotinamide adenine dinucleotide (NAD+) precursor vitamin. 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 for use in dietary supplements. To evaluate the kinetics and dose-dependency of NR oral availability and safety in overweight, but otherwise healthy men and women, an 8-week randomized, double-blind, placebo-controlled clinical trial was conducted. Consumption of 100, 300 and 1000 mg NR dose-dependently and significantly increased whole blood NAD+ (i.e., 22%, 51% and 142%) and other NAD+ metabolites within 2 weeks. The increases were maintained throughout the remainder of the study. There were no reports of flushing and no significant differences in adverse events between the NR and placebo-treated groups or between groups at different NR doses. NR also did not elevate low density lipoprotein cholesterol or dysregulate 1-carbon metabolism. Together these data support the development of a tolerable upper intake limit for NR based on human data.
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]Nicotinamide riboside (NR) is a naturally occurring form of vitamin B3 shown to preferentially elevate the nicotinamide adenine dinucleotide (NAD+) metabolome compared to other vitamin B3 forms (nicotinic acid and nicotinamide). Although daily requirements of vitamin B3 are typically met through the diet, recent studies have shown that additional supplementation with NR may be an effective method to counter the age-related decline in NAD+ levels as NR bypasses the rate-limiting step in NAD+ biosynthesis. Furthermore, pharmaceutical applications of NR for age-related disorders have been proposed. In this study, the safety of a high-purity, nature-identical, synthetic NR (NR-E), manufactured under the guidelines of good manufacturing practices for dietary supplements (21 CFR 111) as well as for drugs (21 CFR 210), was investigated in a 90-day oral toxicity study in Sprague Dawley rats at 300, 500, and 1,200 mg/kg/d. There were no mortality or clinical observations attributable to the test substance at any dose. A small but statistically significant decrease in body weight was observed at day 92 in the 1,200 mg/kg/d NR-treated male rats only. In contrast to a previously published safety assessment using a different synthetic NR (NIAGEN), whose no-observed-adverse-effect-level (NOAEL) was reported to be 300 mg/kg/d, there were no adverse changes in clinical pathology parameters and no notable macroscopic or microscopic findings or treatment-related effects at similar doses. In the current study, the NOAEL for systemic toxicity of NR-E in Sprague-Dawley rats was conservatively determined to be 500 mg/kg/d for males (solely based on body weight) and 1,200 mg/kg/d for females.
Nicotinamide riboside, a trace nutrient in foods, is a vitamin B3 with effects on energy metabolism and neuroprotection. [2021]This review focuses upon the biology and metabolism of a trace component in foods called nicotinamide riboside. Nicotinamide riboside is a precursor of nicotinamide adenine dinucleotide (NAD), and is a source of Vitamin B3. Evidence indicates that nicotinamide riboside has unique properties as a Vitamin B3. We review knowledge of the metabolism of this substance, as well as recent work suggesting novel health benefits that might be associated with nicotinamide riboside taken in larger quantities than is found naturally in foods.
Nicotinamide Riboside-The Current State of Research and Therapeutic Uses. [2021]Nicotinamide riboside (NR) has recently become one of the most studied nicotinamide adenine dinucleotide (NAD+) precursors, due to its numerous potential health benefits mediated via elevated NAD+ content in the body. NAD+ is an essential coenzyme that plays important roles in various metabolic pathways and increasing its overall content has been confirmed as a valuable strategy for treating a wide variety of pathophysiological conditions. Accumulating evidence on NRs' health benefits has validated its efficiency across numerous animal and human studies for the treatment of a number of cardiovascular, neurodegenerative, and metabolic disorders. As the prevalence and morbidity of these conditions increases in modern society, the great necessity has arisen for a rapid translation of NR to therapeutic use and further establishment of its availability as a nutritional supplement. Here, we summarize currently available data on NR effects on metabolism, and several neurodegenerative and cardiovascular disorders, through to its application as a treatment for specific pathophysiological conditions. In addition, we have reviewed newly published research on the application of NR as a potential therapy against infections with several pathogens, including SARS-CoV-2. Additionally, to support rapid NR translation to therapeutics, the challenges related to its bioavailability and safety are addressed, together with the advantages of NR to other NAD+ precursors.