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).
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 Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
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. Blood will be analyzed for NAD-metabolites using spectroscopic assays. 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.
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. Blood will be analyzed for NAD-metabolites using spectroscopic assays. 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.
Haukeland University Hospital
Bergen, Vestland, Norway
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.
Time frame: 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
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.
Time frame: 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
Between-sex differences in the time course of change in the blood NAD-metabolome and cerebral NAD increase, following the administration of oral NRT.
Time frame: 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
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A total of n=6 healthy individuals (3 men and 3 women) will receive NR 1200 mg per day for 4 weeks, followed by 3 weeks of washout. The individuals will undergo repeated blood sampling and 31P-MRS brain scans once per week during the 7 weeks period, Blood will be analyzed for NAD-metabolites using spectroscopic assays.
A total of n=6 individuals with Parkinson's disease (3 men and 3 women) will receive NR 1200 mg per day for 4 weeks, followed by 3 weeks of washout. The individuals will undergo repeated blood sampling and 31P-MRS brain scans once per week during the 7 weeks period, Blood will be analyzed for NAD-metabolites using spectroscopic assays.