NAD-brain: a Pharmacokinetic Study of NAD Replenishment Therapy

Sponsor

Haukeland University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05698771

Collaborator

(none)

Enrollment

Location

Arms

1.5

Anticipated Duration (Months)

3.9

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Healthy	Dietary Supplement: nicotinamide riboside Dietary Supplement: nicotinamide mononucleotide	N/A

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 Design

Study Type:

Interventional

Anticipated Enrollment :

6 participants

Allocation:

Non-Randomized

Intervention Model:

Sequential Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

NAD-brain: a Pharmacokinetic Study of NAD Replenishment Therapy

Anticipated Study Start Date :

Jan 29, 2023

Anticipated Primary Completion Date :

Mar 17, 2023

Anticipated Study Completion Date :

Mar 17, 2023

Arms and Interventions

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.

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.

Outcome Measures

Primary Outcome Measures

NAD metabolism [20 days for NR and 20 days for NMN]
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

Interindividual differences [20 days for NR and 20 days for NMN]
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 [20 days for NR and 20 days for NMN]
Between-sex differences in the time course of change in the blood NAD-metabolome and cerebral NAD increase, following the administration of oral NRT.

Eligibility Criteria

Criteria

Ages Eligible for Study:

35 Years to 85 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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.