NAD-brain: a Pharmacokinetic Study of NAD Replenishment Therapy

Phase 1

Completed

• Conditions: Healthy
• Interventions: Dietary Supplement: nicotinamide riboside; Dietary Supplement: nicotinamide mononucleotide

• Registration Number: NCT05698771
• Lead Sponsor: Haukeland University Hospital

Brief Summary

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).

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 healthy individuals (3 men and 3 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.

Moreover, a total of 6 healthy individuals (3 men and 3 women) and 6 individuals with Parkinson's disease (3 men and 3 women) will receive NR 1200 mg daily (600 mg x 2) for 4 weeks, with a total measurement/assessment period of 7 weeks, and undergo repeated blood sampling and 31P-MRS brain scans once per week during this time.

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 Timeline

• Study Start: 2022-09-17
• Study First Submitted: 2023-01-16
• Study First Submitted QC: 2023-01-16
• Study First Posted: 2023-01-26
• Primary Completion: 2024-03-04
• Study Completion: 2024-03-04
• Status Verified: 2024-09
• Last Update Submitted: 2025-01-16
• Last Update Posted: 2025-01-17

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
NR	nicotinamide riboside	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.
NMN	nicotinamide mononucleotide	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.

Primary Outcome Measures

Name	Time	Method
NAD metabolism	For Stage-1: 20 days for NR and 20 days for NMN comprising 8 days treatment, and 11 days washout. For Stage-2 (NR): 7 weeks comprising 4 weeks of treatment and 3 weeks washout	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.

Secondary Outcome Measures

Name	Time	Method
Interindividual differences	For Stage-1: 20 days for NR and 20 days for NMN comprising 8 days treatment, and 11 days washout. For Stage-2 (NR): 7 weeks comprising 4 weeks of treatment and 3 weeks washout	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.
Between-sex differences	For Stage-1: 20 days for NR and 20 days for NMN comprising 8 days treatment, and 11 days washout. For Stage-2 (NR): 7 weeks comprising 4 weeks of treatment and 3 weeks washout	Between-sex differences in the time course of change in the blood NAD-metabolome and cerebral NAD increase, following the administration of oral NRT.

Trial Locations

Locations (1)

Haukeland University Hospital; 🇳🇴 Bergen, Vestland, Norway