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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: Nicotinamide (NAM); Dietary supplement: Nicotinamide Riboside (NR); Dietary supplement: Nicotinamide Mono Nucleotide (NMN); Dietary supplement: Microcrystalline cellulose

• Study Type: Interventional
• Enrollment (Actual): 68
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Pamela Sun, MBBChir MPhil (Cantab); Phone Number: +41 21 785 81 22; Email: pamela.sun@rd.nestle.com
• Study Contact Backup: Name: Sylviane Oguey-Araymon; Phone Number: +41 21 785-82 79; Email: sylviane.oguey-araymon@rdls.nestle.com

Study Locations

• Switzerland
  • Vaud
    • Lausanne, Vaud, Switzerland, 1000
      • Nestle Clinical Innovation Lab

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy male and female aged 18-50 years, inclusive, at enrolment
2. Body mass index (BMI) between 18.5 to 27.0 kg/m².
3. Able to understand and to sign a written informed consent prior to study enrolment.
4. Willing and able to comply with the requirements for participation in this study.

Exclusion Criteria:

1. Known history of allergy or intolerance to the investigational products.
2. 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.
3. Any acute illness or any recent medical intervention including vaccination within 14 days before the first dose of investigational product.
4. 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.
5. 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.
6. 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.
7. On a self-restricted diet, controlled diet or special therapeutic diet up to 30 days before first dose of investigational product.
8. 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).
9. Current smoker (e.g., cigarette, tobacco, cannabis) who exceeds 5 cigarettes per week.
10. Performing shift work or trans-meridian travel greater than two time zones within 14 days prior to the first dose of investigational product.
11. Currently participating in another research study.
12. Family or hierarchical relationships with the Clinical Innovation Lab (CIL) team.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nicotinamide (NAM)	Dietary supplement: Nicotinamide (NAM); 500 mg a day
Experimental: Nicotinamide Riboside (NR)	Dietary supplement: Nicotinamide Riboside (NR); 1000 mg a day
Experimental: Nicotinamide Mono Nucleotide (NMN)	Dietary supplement: Nicotinamide Mono Nucleotide (NMN); 1000 mg a day
Placebo Comparator: Microcrystalline cellulose	Dietary supplement: Microcrystalline cellulose; 500 mg a day

What is the study measuring?

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.

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comparer the extend the NAD+ precursors (NAM, NR and NMN) affect the NAD+ metabolome in in plasma.	Measure the change in plasma NAD+ metabolites iAUC (reported in microM) and Cmax (microM) determined by quantitative liquid chromatography-mass spectroscopy	over 4 hours at Day 1 and at Day 14.
Comparer the extend the NAD+ precursors (NAM, NR and NMN) affect the NAD+ metabolome in urine	Measure the change in urine NAD+ metabolites iAUC (reported in microM) and Cmax (microM) determined by quantitative liquid chromatography-mass spectroscopy	at baseline Day 14 versus Day 1

Collaborators and Investigators

• Sponsor: Société des Produits Nestlé (SPN)

Study record dates

Study Major Dates

• Study Start (Actual): June 27, 2022
• Primary Completion (Actual): December 30, 2022
• Study Completion (Estimated): December 30, 2023

Study Registration Dates

• First Submitted: July 4, 2022
• First Submitted That Met QC Criteria: August 25, 2022
• First Posted (Actual): August 26, 2022

Study Record Updates

• Last Update Posted (Actual): October 6, 2023
• Last Update Submitted That Met QC Criteria: October 5, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Vasodilator Agents; Antimetabolites; Micronutrients; Hypolipidemic Agents; Lipid Regulating Agents; Vitamins; Vitamin B Complex; Nicotinic Acids; Niacinamide; Niacin
• Other Study ID Numbers: 2201NR

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No