Skip to content NADBrain: A PHARMACOKINETIC STUDY OF NAD REPLENISHMENT THERAPY
Recruiting: NO
ClinicalTrials.gov ID: NCT05698771
Type of study: phase I, interventional, non-randomized, open-label pharmacokinetic clinical trial
Single/multi-center: single-center
Participating countries: Norway
INCLUSION CRITERIA
FOR HEALTHY INDIVIDUALS
Age 30-85 years at the time of enrollment
Neurologically healthy at the time of enrollment
FOR PARTICIPANTS WITH PD
Age 30-85 years at the time of enrollment
Clinical diagnosis of idiopathic PD according to the MDS criteria
Hoehn and Yahr score <4 at time of enrollment (Goetz et al., 2004)
123I-Ioflupane dopamine transporter imaging (DAT-scan) confirming nigrostriatal degeneration
EXCLUSION CRITERIA
GENERAL
History of acute or chronic neurological disorder affecting the central nervous system (CNS). Medical history of migraine, cluster headache, and tension headache was allowed, but not active attacks on the day of the study visits
Any severe somatic illness that would make the individual unable to comply and participate in the study
Any psychiatric disorder that would interfere with compliance in the study
Impaired renal or hepatic function
Severe hematological disease
Mitochondrial disease
Use of high dose vitamin B3 supplementation within 30 days of enrolment
ADDITIONAL CRITERIA FOR PARTICIPANTS WITH PD
Dementia or other neurodegenerative disorders at baseline visit
Diagnosis of atypical parkinsonism (progressive supranuclear palsy, multiple system atrophy or corticobasal degeneration) or vascular parkinsonism
DESIGN
Healthy individuals and individuals with PD are recruited for a pharmacokinetic study of NAD replenishment therapy, using nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN) as biosynthetic precursors. In a first stage, 6 healthy participants (3 men and 3 women) are supplemented with 1200mg NR or NMN for 8 days, followed by a washout period for 11 days. Blood (spectroscopic assay) and brain (31P-MRS) NAD levels are monitored during the whole period. In a second stage, 6 healthy individuals (3 men and 3 women) and 6 individuals with PD (3 men and 3 women) are supplemented with 1200mg NR or NMN for 4 days, followed by a washout period for 3 days. Blood (spectroscopic assay) and brain (31P-MRS) NAD levels are monitored weekly during the whole period.
OBJECTIVES
PRIMARY OBJECTIVE: Determine the change in blood and cerebral NAD levels over time, following the administration of oral NAD replenishment therapy (NRT) with nicotinamide riboside (NR; 1200mg/day) for 8 days and 4 weeks.
SECONDARY OBJECTIVES:
1
Assess the optimal dosing intervals of NRT to maintain a stable increase in cerebral and blood NAD levels during treatment
2
Determine interindividual differences in the time course of change in the blood and cerebral NAD increase following administration of oral NRT
3
Assess sex-dependent differences in the time course of change in the blood NAD-metabolome and cerebral NAD increase following the administration of oral NRT
OUTCOMES
PRIMARY OUTCOME: The change of cerebral NAD levels (measured by 31P-MRS) and of blood NAD levels (measured by the NADMed assay) over time after the administration of oral NRT (8 days and 4 weeks) and during a subsequent washout period (11 days and 3 weeks, respectively).
SECONDARY OUTCOMES:
1. 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 and during the washout period.
2. Between-sex differences in the time course of change in the blood NAD-metabolome and cerebral NAD increase, following the administration of oral NRT.
