NAD-brain: a Pharmacokinetic Study of NAD Replenishment Therapy

Haukeland University Hospital

Status and phase: Completed; Phase 1

Conditions: Healthy

Treatments: Dietary Supplement: nicotinamide mononucleotide; Dietary Supplement: Nicotinamide Riboside (NR)

Study type: Interventional

Funder types: Other

Identifiers

NCT05698771

2023-496197

Details and patient eligibility

About

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).

Full 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.

Enrollment: 12 patients

Sex: All

Ages: 35 to 85 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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12 participants in 4 patient groups

NR Stage-1 Healthy

Experimental group

Description:

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.

Treatment:

Dietary Supplement: Nicotinamide Riboside (NR)

Dietary Supplement: Nicotinamide Riboside (NR)

Dietary Supplement: Nicotinamide Riboside (NR)

NMN Stage-1 Healthy

Experimental group

Description:

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.

Treatment:

Dietary Supplement: nicotinamide mononucleotide

NR Stage 2 Healthy

Experimental group

Description:

A total of 6 healthy individuals (3 men and 3 women) will receive NR 1200 mg daily (600 mg x 2) for for 4 weeks, followed by 3 weeks of washout (total period of follow-up is 7 weeks).

Treatment:

Dietary Supplement: Nicotinamide Riboside (NR)

Dietary Supplement: Nicotinamide Riboside (NR)

Dietary Supplement: Nicotinamide Riboside (NR)

NR Stage-2 Parkinson's disease

Experimental group

Description:

A total of 6 with Parkinson's disease (3 men and 3 women) will receive NR 1200 mg daily (600 mg x 2) for for 4 weeks, followed by 3 weeks of washout (total period of follow-up is 7 weeks).

Treatment:

Dietary Supplement: Nicotinamide Riboside (NR)

Dietary Supplement: Nicotinamide Riboside (NR)

Dietary Supplement: Nicotinamide Riboside (NR)