Nicotinamide Riboside for Patients With Early-Stage Parkinson Disease: The NOPARK Randomized Clinical Trial

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• 95% CI

Importance Nicotinamide riboside, a nicotinamide adenine dinucleotide precursor, has been proposed as a potential disease-modifying therapy for Parkinson disease based on preclinical and early studies. Whether prolonged oral nicotinamide riboside improves clinical outcomes in Parkinson disease is unknown. Objective To determine whether nicotinamide riboside improves clinical outcomes in Parkinson disease compared with placebo. Design, setting, and participants Randomized, double-blind, placebo-controlled, phase 3 clinical trial conducted at 11 centers in Norway. Eligible participants were patients aged 35 years or older with Parkinson disease diagnosed within 2 years before enrollment, Hoehn and Yahr disease stage less than 3, abnormal dopamine transporter scintigraphy findings confirming dopaminergic nigrostriatal denervation, and stable dopaminergic treatment before enrollment. Of 537 screened individuals, 410 were randomized from May 6, 2020, to June 20, 2024, and 393 were included in the primary analysis. Final follow-up was completed on June 19, 2025. Interventions Patients were randomized to receive oral nicotinamide riboside, 500 mg twice daily (n = 206), or matching placebo (n = 204) for 52 weeks. Main outcomes and measures The primary outcome was change from baseline to week 52 in the Movement Disorder Society Unified Parkinson Disease Rating Scale total score (MDS-UPDRS parts I-III; range, 0-236, with higher scores indicating more severe disease; clinically important differences for improvement and worsening, 6.7 and 5.2 points, respectively), analyzed using a mixed model for repeated measures. The 5 key secondary outcomes were the individual parts I, II, and III of the MDS-UPDRS; dopamine transporter single-photon emission computed tomography brain imaging findings; and the Non-Motor Symptoms Scale score (NMSS; range, 0-360, with higher scores indicating greater nonmotor symptom burden). Results Among the 393 participants in the primary analysis, the mean age was 65.6 (SD, 9.4) years and 133 (34%) were female. At week 52, the total MDS-UPDRS score increased by 2.45 (95% CI, 0.80-4.10) points with nicotinamide riboside and decreased by 0.27 (95% CI, -1.95 to 1.40) points with placebo, yielding an adjusted mean difference of 2.72 points (95% CI, 0.47-4.98 points; P = .02), favoring placebo. Of the 5 prespecified key secondary outcomes, 4 showed no significant difference, but nonmotor symptom burden worsened more with nicotinamide riboside (NMSS score adjusted mean difference, 4.22 [95% CI, 1.07-7.37] points; P = .009). Serious adverse events occurred in 17 (8.3%) of 205 participants receiving nicotinamide riboside and 29 (14.1%) of 205 receiving placebo in the safety population. Conclusions and relevance Among patients with early Parkinson disease, nicotinamide riboside treatment for 52 weeks did not improve clinical outcomes and was associated with worse clinical outcomes than placebo. These findings do not support nicotinamide riboside as a disease-modifying treatment for Parkinson disease. Trial registration ClinicalTrials.gov Identifier: NCT03568968.

Brage Brakedal, Geir Olve Skeie, Carlotta Derad, Karl Bjørnar Alstadhaug, Ingunn Anundskås, Haakon Berven, Martin Biermann, Kari Anne Bjørnarå, Yamila N Torres Cleuren, Solveig E J Dalbro, David Eidelberg, Kjartan Foldnes, Gabriela Fortes, Kristoffer Haugarvoll, Karen Herlofson, Eldbjørg Hustad, Roelfien Ida HogenEsch, Gard Aasmund Skulstad Johanson, Stein Harald Johnsen, Krisztina Kunszt, Simon Kverneng, Aliaksei Labusau, Ingeborg Haugesag Lie, Hallvard Lilleng, Katarina Lundervold, Christofer Lundqvist, Yilong Ma, Adrian McCann, Tormund Haugland Njølstad, Lasse Pihlstrøm, et al.

Leverage2 / 5

Reusable within one subfield (a technique, dataset, or protocol a few groups will adopt).

10% of this desk’s rubric

Magnitude3 / 5

Large gain: roughly 2x, or a clear new state of the art on a hard, unsaturated problem.

20% of this desk’s rubric

Evidence5 / 5

Definitive: phase 3 randomized evidence on hard endpoints, multi-lab replication, or community verification at scale.

32% of this desk’s rubric

Novelty3 / 5

A genuinely new approach to an open problem.

8% of this desk’s rubric

Trajectory2 / 5

Some room to improve with obvious engineering.

5% of this desk’s rubric

Stakes2 / 5

Benefits a professional community (practitioners, clinicians, engineers).

25% of this desk’s rubric

• Citations0 (reference 20, via openalex, Oct 17, 2026, 06:17 UTC)

• Reviewed by heuristic-v7 on Oct 18, 2026, 06:17 UTC. Paper type: clinical.
• Categories: Journal Article
• BRIEF, No.1 in the Medicine edition of October 18, 2026.