Effect of Oral NAD+ Precursors Administration on Blood NAD+ Concentration in Healthy Adults

Study Overview
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Brief Summary
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Nicotinamide adenine dinucleotide (NAD) is a coenzyme playing a central role in human metabolic pathways. A recognized approach to increase NAD level is through oral supplementation of its precursors promoting NAD synthesis in vivo. NAD precursors exist in multiple forms. However, it is unclear how the various precursors compare in their ability to increase NAD levels in human blood. The purpose of this study is to compare the effect of 3 NAD precursors on whole blood NAD metabolome.

Official Title
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Effect of Oral NAD+ Precursors Administration on Blood NAD+ Concentration in Healthy Adults

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: Nicotinamide (NAM)
* Dietary Supplement: Nicotinamide Riboside (NR)
* Dietary Supplement: Nicotinamide Mono Nucleotide (NMN)
* Dietary Supplement: Microcrystalline cellulose


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male and female aged 18-50 years, inclusive, at enrolment Body mass index (BMI) between 18.5 to 27.0 kg/m². Able to understand and to sign a written informed consent prior to study enrolment. Willing and able to comply with the requirements for participation in this study. Exclusion Criteria: Known history of allergy or intolerance to the investigational products. Any chronic medical condition and/or history of significant medical condition, which in the opinion of the site physician/ investigator may risk participant wellbeing/ safety, impede participant compliance with study procedures or ability to complete the study and/ or could confound the primary objectives of the study. Any acute illness or any recent medical intervention including vaccination within 14 days before the first dose of investigational product. Female participants who are pregnant or intending to become pregnant, lactating and/or breastfeeding. Women of childbearing potential who are not currently using medically effective forms of contraception. Use of prescription drugs known to potentially interact with NAD precursors within 14 days or 5 half-lives (whichever is longer) prior to the first dose of investigational product. Use of multivitamin/ multimineral supplements, NAD+ precursor supplementation (e.g., niacin, nicotinic acid or niacinamide), L-tryptophan supplementation and/ or any over-the- counter (OTC) medication promoting healthy aging or anti-aging or longevity up to 30 days before first dose of investigational product. On a self-restricted diet, controlled diet or special therapeutic diet up to 30 days before first dose of investigational product. Average alcohol consumption greater than 2 standard drinks per day over a week for males, and greater than 1 standard drink per day over a week for females. One standard drink contains 10-12 g of ethanol. Examples of standard drinks are one beer can (300 ml), one glass of wine (100 ml) or one glass of schnaps (30 ml). Current smoker (e.g., cigarette, tobacco, cannabis) who exceeds 5 cigarettes per week. Performing shift work or trans-meridian travel greater than two time zones within 14 days prior to the first dose of investigational product. Currently participating in another research study. Family or hierarchical relationships with the Clinical Innovation Lab (CIL) team.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 50 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: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Nicotinamide (NAM)<br> | Dietary Supplement: Nicotinamide (NAM)<br>* 500 mg a day<br>|
| Experimental: Nicotinamide Riboside (NR)<br> | Dietary Supplement: Nicotinamide Riboside (NR)<br>* 1000 mg a day<br>|
| Experimental: Nicotinamide Mono Nucleotide (NMN)<br> | Dietary Supplement: Nicotinamide Mono Nucleotide (NMN)<br>* 1000 mg a day<br>|
| Placebo Comparator: Microcrystalline cellulose<br> | Dietary Supplement: Microcrystalline cellulose<br>* 500 mg a day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the extent of increase in NAD+ level in whole blood, for each NAD+ precursor (NAM, NR and NMN) compared to placebo | Measure the changes in whole blood NAD+ level interventions vs placebo: NAM vs placebo, NR vs placebo, NMN versus placebo by quantitative liquid chromatography-mass spectroscopy | at Day 14 | 
| Compare the extent of increase in NAD+ level in whole blood across the 3 NAD+ precursors (NAM, NR and NMN) | Measure the changes in whole blood NAD+ level across interventions: NAM vs NR, NAM vs NMN, NR vs NMN by quantitative liquid chromatography-mass spectroscopy | at Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the extent the NAD+ precursors(NAM, NR and NMN) affect the NAD metabolome in whole blood compared to placebo | Measure the change in whole blood NAD+ metabolites iAUC (reported as microM*h) and Cmax (microM) by quantitative liquid chromatography-mass spectroscopy | over 4 hours at Day 1 and at Day 14. | 
| Compare the extent the NAD+ precursors (NAM, NR and NMN) affect the NAD+ metabolome in whole blood. | Measure the change in whole blood NAD+ metabolites iAUC (reported as microM*h) and Cmax (microM) determined by quantitative liquid chromatography-mass spectroscopy | over 4 hours at Day 1 and at Day 14. |