Clinical trial NCT05698771: NAD-brain: a Pharmacokinetic Study of NAD Replenishment Therapy
Official title: NAD-brain: a Pharmacokinetic Study of NAD Replenishment Therapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Keywords: nicotinamide adenine dinucleotide
NAD
NAD+
pharmacokinetics
nicotinamide riboside
nicotinamide mononucleotide
brain kinetics
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
First posted: 2023-01-26
Enrollment: 12
Sex: ALL
Minimum age (years): 35
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: NAD metabolism
timeFrame: 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
Secondary outcomes:
measure: Interindividual differences
timeFrame: 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
measure: Between-sex differences
timeFrame: 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
Other outcomes:
Locations:
city: Bergen
country: Norway
facility: Haukeland University Hospital
state: Vestland
Study officials:
affiliation: Haukeland University Hospital
name: Charalampos Tzoulis, MD, PhD
role: STUDY_DIRECTOR
References: