Safety & Efficacy of Nicotinamide Riboside Supplementation for Improving Physiological Function in Middle-Aged and Older Adults

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy of supplementation with the Nicotinamide Adenine Dinucleotide (NAD+) precursor compound, Nicotinamide Riboside (NR), for improving physiological function (vascular, motor, and cognitive) in healthy middle-aged and older adults.

Detailed Description
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Overall, the proposed research project has the long-term potential to influence clinical practice by establishing novel therapies for treating multiple domains of age-associated physiological dysfunction and thereby reducing the risk of clinical disease and disability.

Official Title
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Safety & Efficacy of Nicotinamide Riboside Supplementation for Improving Physiological Function in Middle-Aged and Older Adults

Conditions
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Aging

Intervention / Treatment
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* Dietary Supplement: Niagen™
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to provide informed consent Baseline brachial flow-mediated dilation (FMD) < 6%Δ (rationale: non-invasive screening to ensure exclusion of subjects with exceptionally high baseline endothelial function. Ability to perform motor and cognitive tests (e.g., can rise from a chair, walk for 2 min, climb 10 stairs) Women will be confirmed as postmenopausal (either natural or surgical) based on cessation of menses for >1 year. Exclusion Criteria: ages <55 years or ≥80 years body mass index (BMI) >40 kg/m2 (rationale: vascular function and blood pressure measurements can be inaccurate in severely obese subjects and these subjects may differ in many ways from normal weight, overweight or less obese subjects) not weight stable in the prior 3 months (>2 kg weight change) or unwilling to remain weight stable throughout study (rationale: recent weight change or weight loss can influence vascular function) having unstable angina, acute myocardial infarction, coronary angioplasty, or aorto-coronary bypass surgery as defined by the occurrence of an event, symptom, surgery, or change in medication and/or dosage within 3 months prior to enrollment having thyroid disease that is not controlled by medications or <3 month's use of a particular medication and/or dosage (rationale: uncontrolled thyroid diseases are associated with alterations in vascular function) having past or present alcohol dependence or abuse, as defined by the American Psychiatry Association, Diagnostic and Statistical Manual of Mental Disorders abnormal blood chemistries for renal and liver function (>1 standard deviation outside the normal range) Moderate or severe peripheral artery disease (ankle-brachial index <0.7). Insufficient health to participate in a VO2max test based on a physical examination and/or graded exercise test (this will be determined in accordance with stated contraindications for exercise testing provided by the American Heart Association).

Ages Eligible for Study
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Minimum Age: 55 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>placebo, 500 mg, 2x/day for 6 weeks | Dietary Supplement: Placebo<br>* silicified microcrystalline cellulose, vegetarian capsule<br>|
| Active Comparator: Niagen™<br>Niagen™ (nicotinamide riboside chloride, ChromaDex, Inc.) 500mg, 2x/day for 6 weeks. | Dietary Supplement: Niagen™<br>* nicotinamide riboside chloride, 250mg capsules<br>* Other names: Nicotinamide Riboside;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of treatment emergent adverse events | self reported side effects, vital signs, hematology, liver enzymes, markers of kidney function and blood chemistry | 6 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelium Dependent Dilation | Brachial Artery Flow-Mediated Dilation (FMD) | 6 weeks | 
| Arterial Stiffness | Aortic Pulse Wave Velocity (PWV) | 6 weeks | 
| Cognitive Function | NIH Toolbox Cognitive Function Battery | 6 weeks | 
| Motor Function | NIH Toolbox Motor Function Battery | 6 weeks | 
| Systemic markers of oxidative stress and inflammation | Assessment of plasma C-reactive protein (CRP) and circulating and mononuclear cell-derived cytokine and antioxidant expression. | 6 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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aging, nicotinamide riboside, arterial stiffness, endothelial dysfunction