Clinical trial NCT03568968: A Randomized Controlled Trial of Nicotinamide Riboside Supplementation in Early Parkinson's Disease
Official title: A Randomized Controlled Trial of Nicotinamide Riboside Supplementation in Early Parkinson's Disease: the NOPARK Study
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE3
Conditions: Parkinson Disease
Keywords: Parkinson's Disease
NAD metabolism
Mitochondria
Nicotinamide Riboside
Lead sponsor: Haukeland University Hospital
Sponsor class: OTHER
First posted: 2018-06-26
Enrollment: 400
Sex: ALL
Minimum age (years): 35
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized double-blinded study. N = 400 participants are randomized in a 1:1 ratio to either nicotinamide riboside (500 mg x 2 per day) or placebo.
Primary purpose: TREATMENT

Brief summary: NOPARK is a double-blinded randomized controlled phase II trial, with the aim to assess the efficacy of nicotinamide adenine dinucleotide (NAD)-replenishment therapy in the form of oral nicotinamide riboside (NR) in delaying the progression of early Parkinson's disease (PD). A total of 400 persons with early stage Parkinson's disease will be enrolled, randomized on nicotinamide riboside (NR) 500mg x 2 per day or placebo, and followed for 52 weeks.

Detailed description: NOPARK is a multi-center, double-blinded randomized controlled trial, with the aim to assess the efficacy of NAD-replenishment therapy in the form of oral nicotinamide riboside (NR) in delaying the progression of early Parkinson's disease (PD). Individuals with PD (n = 400) will be recruited from multiple centers across Norway. Eligible participants must have been diagnosed with PD within 2 years of study enrollment and meet the trial's inclusion criteria. All participants will be given a standard PD-treatment regimen comprising selegiline 10 mg/day and oral levodopa (Sinemet or Madopar) at a dose of 100mg x 3, 150mg x3, or 200mg x 3 per day. The PD-treatment regimen will be frozen at baseline and remain stable throughout the duration of the study. At baseline, participants will be randomized on a 1:1 ratio on either nicotinamide riboside (NR) 500mg x 2 per day or placebo. Both the participants and the investigators will be blinded. The trial duration will be 52 weeks, during which participants will be assessed at baseline, 13, 26, 39 and 52 weeks. Measures include clinical evaluation using established scales for motor and non-motor dysfunction, as well as quality of life, 123I-N-ω-fluoropropyl-2β-carbomethoxy-3β-(4-iodophenyl) nortropane (\[¹²³I\]FP-CIT) single photon emission tomography (DaTscan), magnetic resonance imaging (MRI) of the brain, blood safety tests, and blood sampling for metabolomics, transcriptomics, and other exploratory analyses. The primary outcome of the study is the total score of the Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS).

Eligibility criteria: Inclusion Criteria:

* Have a clinical diagnosis of idiopathic PD according to the MDS clinical diagnostic criteria for Parkinson's disease
* \[¹²³I\]FP-CIT single photon emission CT (DaTscan) confirming nigrostriatal degeneration
* Diagnosed with PD within 2 years from enrolment
* Hoehn and Yahr score \< 3 at enrolment
* Optimal symptomatic therapy, not requiring adjustments, for at least 1 month.
* Age equal to or greater than 35 years at time of enrolment.

Exclusion Criteria:

* Dementia or other neurodegenerative disorder at baseline visit
* Diagnosed with atypical parkinsonism or vascular parkinsonism
* 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.
* Use of high dose vitamin B3 supplementation within 30 days of enrolment
* Metabolic, neoplastic, or other physically or mentally debilitating disorder at baseline visit.
* Genetically confirmed mitochondrial disease

Primary outcomes:
measure: Disease severity assessed by the total MDS-UPDRS (Movement Disorder Society Unified Parkinson's Disease rating Scale) subsections I-III
timeFrame: 52 weeks
Secondary outcomes:
measure: Change in the severity of nigrostriatal degeneration assessed by [¹²³I]FP-CIT single photon emission CT (DaTscan)
timeFrame: 52 weeks
measure: Change in the clinical severity of non-motor symptoms assessed by the Non-Motor Symptoms Assessment Scale
timeFrame: 52 weeks
measure: Change in the clinical severity of cognitive decline assessed by the Montreal Cognitive Assessment (MoCA) scale
timeFrame: 52 weeks
measure: Change in quality of life assessed by the EuroQuality of Life Five Dimensions (EQ-5D-5L) questionnaire.
timeFrame: 52 weeks
Other outcomes:
Locations:
city: Arendal
country: Norway
facility: Arendal Hospital
city: Bergen
country: Norway
facility: Haukeland University Hospital
city: Drammen
country: Norway
facility: Vestre Viken Hospital
city: Førde
country: Norway
facility: Førde sykehus
city: Haugesund
country: Norway
facility: Haugesund Hospital
city: Molde
country: Norway
facility: Molde sjukehus
city: Oslo
country: Norway
facility: Akershus university hospital
city: Oslo
country: Norway
facility: Oslo University Hospital
Study officials:
affiliation: Haukeland University Hospital
name: Charalampos Tzoulis, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: