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This phase 3 randomized, double-blind, placebo-controlled trial investigated whether nicotinamide riboside, a precursor of nicotinamide adenine dinucleotide (NAD), could improve clinical outcomes in early-stage Parkinson disease. A total of 410 participants were randomized to oral nicotinamide riboside 500 mg twice daily (n = 206) or placebo (n = 204) for 52 weeks; 393 participants were included in the primary analysis. The primary outcome was change in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score, with higher scores indicating greater impairment. At week 52, the score increased by 2.45 points (95% CI, 0.80–4.10) in the nicotinamide riboside group and decreased by 0.27 points (95% CI, −1.95 to 1.40) with placebo. The adjusted between-group difference was 2.72 points (95% CI, 0.47–4.98; P = 0.02), favouring placebo. Nonmotor symptom burden also worsened more with nicotinamide riboside (adjusted mean difference, 4.22; 95% CI, 1.07–7.37; P = 0.009). Serious adverse events occurred in 8.3% of participants receiving nicotinamide riboside and 14.1% receiving placebo. Conclusion: Nicotinamide riboside did not improve clinical outcomes and was associated with modestly greater worsening than placebo. The findings do not support its use as a disease-modifying or symptomatic treatment for Parkinson disease.
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This phase 3 randomized, double-blind, placebo-controlled trial investigated whether nicotinamide riboside, a precursor of nicotinamide adenine dinucleotide (NAD), could improve clinical outcomes in early-stage Parkinson disease. A total of 410 participants were randomized to oral nicotinamide riboside 500 mg twice daily (n = 206) or placebo (n = 204) for 52 weeks; 393 participants were included in the primary analysis. The primary outcome was change in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) total score, with higher scores indicating greater impairment. At week 52, the score increased by 2.45 points (95% CI, 0.80–4.10) in the nicotinamide riboside group and decreased by 0.27 points (95% CI, −1.95 to 1.40) with placebo. The adjusted between-group difference was 2.72 points (95% CI, 0.47–4.98; P = 0.02), favouring placebo. Nonmotor symptom burden also worsened more with nicotinamide riboside (adjusted mean difference, 4.22; 95% CI, 1.07–7.37; P = 0.009). Serious adverse events occurred in 8.3% of participants receiving nicotinamide riboside and 14.1% receiving placebo. Conclusion: Nicotinamide riboside did not improve clinical outcomes and was associated with modestly greater worsening than placebo. The findings do not support its use as a disease-modifying or symptomatic treatment for Parkinson disease.
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