A Randomized Controlled Trial of Nicotinamide Riboside Supplementation in Early Parkinson's Disease

Parkinson Disease Clinical Trial

— NOPARK  

Official title:

A Randomized Controlled Trial of Nicotinamide Riboside Supplementation in Early Parkinson's Disease: the NOPARK Study

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT03568968
• Other study ID #: 2017/2083
• Status: Recruiting
• Phase: Phase 3
• Start date: May 15, 2020
• Est. completion date: April 30, 2025

Study information

• Verified date: April 2024
• Source: Haukeland University Hospital
• Contact: Charalampos Tzoulis, MD, PhD
• Phone: 94392305
• Email: charalampos.tzoulis[@]helse-bergen.no
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 400
• Est. completion date: April 30, 2025
• Est. primary completion date: December 31, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 35 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Parkinson Disease

Intervention

Dietary Supplement:
• Nicotinamide Riboside
Nicotinamide Riboside 500mg administered two times a day. Given as capsules. Duration of the trial; 52 weeks.

Other:
• Placebo
Placebo drug, administered two times a day. Given as capsules. Duration of the trial; 52 weeks.

Locations

Country	Name	City	State
Norway	Arendal Hospital	Arendal
Norway	Haukeland University Hospital	Bergen
Norway	Vestre Viken Hospital	Drammen
Norway	Førde sykehus	Førde
Norway	Haugesund Hospital	Haugesund
Norway	Molde sjukehus	Molde
Norway	Akershus university hospital	Oslo
Norway	Oslo University Hospital	Oslo

Sponsors (1)

Lead Sponsor	Collaborator
Haukeland University Hospital

Country where clinical trial is conducted

Norway, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Disease severity assessed by the total MDS-UPDRS (Movement Disorder Society Unified Parkinson's Disease rating Scale) subsections I-III	The Movement Disorder Society Unified Parkinson's Disease rating Scale (MDS-UPDRS) measures multiple clinical disabilities, each on a scale of 1-4. The subscores are summed providing a total score for MDS-UPDRS. The total score ranges from 0 to 260. Higher score indicates worse outcome. Here, the total score of MDS-UPDRS sections 1-3 will be used.	52 weeks
Secondary	Change in the severity of nigrostriatal degeneration assessed by [¹²³I]FP-CIT single photon emission CT (DaTscan)	[¹²³I]FP-CIT single photon emission CT (DaTscan)	52 weeks
Secondary	Change in the clinical severity of non-motor symptoms assessed by the Non-Motor Symptoms Assessment Scale	Non-Motor Symptoms Scale (NMSS) has 30 items, score range is 0-360 with higher scores indicating a worse outcome.	52 weeks
Secondary	Change in the clinical severity of cognitive decline assessed by the Montreal Cognitive Assessment (MoCA) scale	Montreal Cognitive Assessment (MoCA), score range is 0-30 with lower scores indicating a worse outcome.	52 weeks
Secondary	Change in quality of life assessed by the EuroQuality of Life Five Dimensions (EQ-5D-5L) questionnaire.	Quality of Life assessment (EuroQuality of Life Five Dimensions - EQ-5D-5L).	52 weeks