NAD-brain: a Pharmacokinetic Study of NAD Replenishment Therapy (NAD-brain)

The objective of the NAD-brain study is to determine the blood and brain pharmacokinetics of NAD replenishment therapy (NRT) using Nicotinamide Riboside (NR) or Nicotinamide Mononucleotide (NMN).

Study Overview

• Status: Recruiting
• Conditions: Healthy
• Intervention / Treatment: Dietary supplement: nicotinamide riboside; Dietary supplement: nicotinamide mononucleotide

Detailed Description

The NAD-brain study will perform a parallel assessment of NAD replenishment therapy (NRT) pharmacokinetics in the blood and brain of healthy human subjects. A total of 6-10 healthy individuals (3-5 men and 3-5 women) will undergo repeated blood sampling and 31P-MRS brain scans during two 20-day periods, each of which will start with 8 days of daily intake of Nicotinamide Riboside (NR) 600mg x 2, or Nicotinamide Mononucleotide (NMN) 600mg x 2. The two 20-day periods will be 14 days apart to allow for washout of the previous compound. Blood will be analyzed for NAD-metabolites. The simultaneous change in NAD-metabolism over time in blood and brain will be assessed and blood and brain pharmacokinetics for NRT in humans will be established.

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Charalampos Tzoulis, MD, PhD; Phone Number: +47 94392305; Email: charalampos.tzoulis@uib.no
• Study Contact Backup: Name: Christian Dölle, PhD; Phone Number: +47 46784849; Email: Christian.Doelle@uib.no

Study Locations

• Norway
  • Vestland
    • Bergen, Vestland, Norway, 5021
      • Recruiting
      • Haukeland University Hospital
      • Contact: Charalampos Tzoulis, MD, PhD; Phone Number: +47 94392305; Email: charalampos.tzoulis@helse-bergen.no
      • Contact: Christian Dölle, PhD; Phone Number: +47 46784849; Email: Christian.Doelle@uib.no
      • Principal Investigator: Charalampos Tzoulis, MD, PhD
      • Sub-Investigator: Christian Dölle, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 35 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age 30-85 years at the time of enrollment.
• Neurologically healthy at the time of enrollment.

Exclusion Criteria:

• History of acute or chronic neurological disorder affecting the central nervous system (CNS). Migraine, cluster headache, and tension headache are allowed, but not on the day of the study visits.
• Impaired renal function.
• Impaired hepatic function.
• Severe hematological disease.
• Any psychiatric disorder that would interfere with compliance in the study.
• Any severe somatic illness that would make the individual unable to comply and participate in the study.
• Mitochondrial disease.
• Use of high dose vitamin B3 supplementation within 30 days of enrolment.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NR; A total of 6 individuals comprising 3 males and 3 females will receive NR 1200 mg daily (600 mg x 2) for 8 days, with a total measurement/assessment period of 20 days. These will be the same individuals as in the NMN-arm. The individuals will enter the two arms sequentially and with a washout period of 14 days.	Dietary supplement: nicotinamide riboside; The NAD-brain study will perform a parallel assessment of NAD replenishment therapy (NRT) pharmacokinetics in the blood and brain of healthy human subjects . A total of 6-10 healthy individuals (3-5 men and 3-5 women) will undergo repeated blood sampling and 31P-MRS brain scans during two 20-day periods, each of which will start with 8 days of daily intake of Nicotinamide Riboside (NR) 600mg x 2, or Nicotinamide Mononucleotide (NMN) 600mg x 2. The two 20-day periods will be 14 days apart to allow for washout of the previous compound. Blood will be analyzed for NAD-metabolites using HPLC-MS. By this approach we will measure the simultaneous change in NAD-metabolism over time in blood and brain and establish blood and brain pharmacokinetics for NRT in humans. Based on these results we will determine the optimal dosing frequency of NRT in healthy individuals.
Experimental: NMN; A total of 6 individuals comprising 3 males and 3 females will receive NMN 1200 mg daily (600 mg x 2) for 8 days, with a total measurement/assessment period of 20 days. These will be the same individuals as in the NR-arm. The individuals will enter the two arms sequentially and with a washout period of 14 days.	Dietary supplement: nicotinamide mononucleotide; The NAD-brain study will perform a parallel assessment of NAD replenishment therapy (NRT) pharmacokinetics in the blood and brain of healthy human subjects . A total of 6-10 healthy individuals (3-5 men and 3-5 women) will undergo repeated blood sampling and 31P-MRS brain scans during two 20-day periods, each of which will start with 8 days of daily intake of Nicotinamide Riboside (NR) 600mg x 2, or Nicotinamide Mononucleotide (NMN) 600mg x 2. The two 20-day periods will be 14 days apart to allow for washout of the previous compound. Blood will be analyzed for NAD-metabolites using HPLC-MS. By this approach we will measure the simultaneous change in NAD-metabolism over time in blood and brain and establish blood and brain pharmacokinetics for NRT in humans. Based on these results we will determine the optimal dosing frequency of NRT in healthy individuals.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NAD metabolism	The change of cerebral NAD levels (measured by 31P-MRS) and of blood NAD-metabolites (measured by HPLC-MS), over time (20 days), after the administration of oral NRT with the following NAD precursors: NR 600mg x 2 daily, NMN 600mg x 2 daily.	20 days for NR and 20 days for NMN

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Interindividual differences	Descriptive analyses of interindividual differences in the time course of change in the blood NAD-metabolome and cerebral NAD increase, following the administration of oral NRT.	20 days for NR and 20 days for NMN
Between-sex differences	Between-sex differences in the time course of change in the blood NAD-metabolome and cerebral NAD increase, following the administration of oral NRT.	20 days for NR and 20 days for NMN

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Investigators: Study Director: Charalampos Tzoulis, MD, PhD, Haukeland University Hospital

Study record dates

Study Major Dates

• Study Start (Anticipated): January 29, 2023
• Primary Completion (Anticipated): March 17, 2023
• Study Completion (Anticipated): March 17, 2023

Study Registration Dates

• First Submitted: January 16, 2023
• First Submitted That Met QC Criteria: January 16, 2023
• First Posted (Actual): January 26, 2023

Study Record Updates

• Last Update Posted (Actual): January 27, 2023
• Last Update Submitted That Met QC Criteria: January 25, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: pharmacokinetics; NAD+; NAD; nicotinamide riboside; nicotinamide adenine dinucleotide; nicotinamide mononucleotide; brain kinetics
• 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: 2023-496197

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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