NAD-brain: a Pharmacokinetic Study of NAD Replenishment Therapy

Study Overview
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Brief Summary
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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
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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.

Official Title
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NAD-brain: a Pharmacokinetic Study of NAD Replenishment Therapy

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: nicotinamide riboside
* Dietary Supplement: nicotinamide mononucleotide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 35 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NR<br>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<br>* 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.<br>|
| Experimental: NMN<br>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<br>* 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.<br>|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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NAD, nicotinamide adenine dinucleotide, NAD+, pharmacokinetics, nicotinamide riboside, nicotinamide mononucleotide, brain kinetics