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

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

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.

Study Overview

• Status: Completed
• Conditions: Parkinson Disease
• Intervention / Treatment: Dietary supplement: Nicotinamide Riboside; Other: Placebo

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).

• Study Type: Interventional
• Enrollment (Actual): 410
• Phase: Phase 3

Contacts and Locations

Study Locations

• Norway
  • Arendal, Norway
    • Arendal Hospital
  • Bergen, Norway
    • Haukeland University Hospital
  • Drammen, Norway
    • Vestre Viken Hospital
  • Førde, Norway
    • Førde sykehus
  • Haugesund, Norway
    • Haugesund Hospital
  • Molde, Norway
    • Molde Sjukehus
  • Oslo, Norway
    • Oslo University Hospital
  • Oslo, Norway
    • Akershus University Hospital
  • Tromsø, Norway
    • University Hospital of North Norway
  • Nordland
    • Bodø, Nordland, Norway
      • Bodø Hospital
  • Østland
    • Fredrikstad, Østland, Norway
      • Østfold Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Nicotinamide Riboside; nicotinamide riboside, 1000mg daily for the duration of the trial (52 weeks). Dosage form is capsules.	Dietary supplement: Nicotinamide Riboside; Nicotinamide Riboside 500mg administered two times a day. Given as capsules. Duration of the trial; 52 weeks.; Other Names: NR, NAD, TruNiagen
Placebo Comparator: Placebo Comparator; Placebo capsules, no active ingredients.	Other: Placebo; Placebo drug, administered two times a day. Given as capsules. Duration of the trial; 52 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Disease severity assessed by the total MDS-UPDRS (Movement Disorder Society Unified Parkinson's Disease rating Scale): sum of subsections I, II, and III	The Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) assesses motor and non-motor symptoms of PD through four parts, with individual items rated on a 0-4 scale. Subscores are summed to provide a total score ranging from 0 to 260, with higher scores indicating greater disability. The primary outcome will be the MDS-UPDRS Total Score (sum of parts I, II, and III).	From baseline to the end of treatment at 52 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of motor symptoms in PD.	Change from baseline in the MDS-UPDRS Part III in the ON-medication state.	From baseline to the end of treatment at 52 weeks
Severity of dopaminergic nigrostriatal denervation, assessed by [¹²³I]FP-CIT single photon emission CT (DaTscan)	Change from baseline in the mean striatal binding ratio (SBR) of the putamen, bilaterally, as measured [¹²³I]FP-CIT Single-Photon Emission Computed Tomography (SPECT) Imaging of the Dopamine Transporter (DaT, DaTscan).	From baseline to the end of treatment at 52 weeks
Severiy of non-motor symptoms in daily living in PD	Change from baseline in the MDS-UPDRS Part I in the ON-medication state	From baseline to the end of treatment at 52 weeks
Severity of motor aspects of experiences of daily living in PD.	Change from baseline in the MDS-UPDRS Part II	From baseline to the end of treatment at 52 weeks
Severity of non-motor symptoms of PD assessed by the Non-Motor Symptoms Assessment Scale	Change from baseline in the NMSS Score in the ON-medication state. Non-Motor Symptoms Scale (NMSS) has 30 items, score range is 0-360 with higher scores indicating a worse outcome.	From baseline to the end of treatment at 52 weeks
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.	From baseline to the end of treatment at 52 weeks
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).	From baseline to the end of treatment at 52 weeks
Hoehn and Yahr stage of PD	Hoehn and Yahr scale distinguishes between five stages in PD: Stage 1: Unilateral disease; Stage 2: Bilateral disease without impairment of balance; Stage 3: Bilateral disease with postural instability but physically independent; Stage 4: Severe disability; still able to walk or stand unassisted; Stage 5: Confinement to bed or wheelchair unless aided.	From baseline to the end of treatment at 52 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
brain nicotinamide adenine dinucleotide (NAD) levels	Change from baseline in brain NAD/ATP-α ratio measured by 31 Phosphorus magnetic resonance spectroscopy (31P-MRS) in the posterior brain (encompassing the occipital, parietooccipital and posterior parts of the temporal cortex).	From baseline to the end of treatment at 52 weeks
systemic nicotinamide adenine dinucleotide (NAD) metabolism	Change from baseline in the NAD metabolome in whole blood or PBMC, measured by liquid chromatography mass spectrometry (LC-MS): Nicotinamide adenine dinucleotide oxidized (NAD+), Nicotinamide adenine dinucleotide reduced (NADH), NAD+/NADH ratio, total NAD (sum of NAD+ and NADH), Nicotinamide adenine dinucleotide phosphate oxidized (NADP+), Nicotinamide adenine dinucleotide phosphate reduced (NADPH), NADP+/NADPH ratio, total NADP (sum of NADP+ and NADPH, 1-methyl nicotinamide (Me-Nam), nicotinic acid-adenine dinucleotide (NAAD), N1-methyl-2-pyridone-5-carboxamide (Me-2-PY), Nicotinamide (Nam), Nicotinamide N-oxide (Nam N-oxide), ADP-ribose (ADPR), Nicotinic acid riboside (NAR), Nicotinamide riboside (NR), Nicotinamide mononucleotide (NMN), Nicotinic acid (NA).	From baseline to the end of treatment at 52 weeks
neurofilament light-chain (NfL) levels	Change from baseline in serum neurofilament light-chain (NfL) levels, measured by Simoa analysis.	From baseline to the end of treatment at 52 weeks
Safety and tolerablity	Report of all Adverse Events (AE) of moderate or severe intensity and Serious Adverse Events (SAE).	From baseline to the end of treatment at 52 weeks

Collaborators and Investigators

• Sponsor: Haukeland University Hospital
• Collaborators: Oslo University Hospital; Ostfold Hospital Trust; Sorlandet Hospital HF; Helse Fonna; University Hospital, Akershus; Molde Hospital; Drammen sykehus; Bodø sykehus; University Hospital of Northern Norway, Tromsø, Norway; Førde Hospital Trust
• Investigators: Principal Investigator: Charalampos Tzoulis, MD, PhD, Haukeland University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2020
• Primary Completion (Actual): June 17, 2025
• Study Completion (Actual): June 17, 2025

Study Registration Dates

• First Submitted: June 14, 2018
• First Submitted That Met QC Criteria: June 14, 2018
• First Posted (Actual): June 26, 2018

Study Record Updates

• Last Update Posted (Estimated): September 26, 2025
• Last Update Submitted That Met QC Criteria: September 23, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Parkinson's Disease; Mitochondria; Nicotinamide Riboside; NAD metabolism
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Nucleic Acids, Nucleotides, and Nucleosides; Enzymes and Coenzymes; Purines; Coenzymes; Ribonucleotides; Nucleotides; Adenine Nucleotides; Purine Nucleotides; nicotinamide-beta-riboside; NAD
• Other Study ID Numbers: 2017/2083

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No