Nicotinamide riboside of no benefit in Parkinson's disease

In the treatment of patients with Parkinson disease (PD), nicotinamide riboside does not appear to confer beneficial effects and is even associated with worse clinical outcomes compared with placebo, according to a phase III trial.

Researchers enrolled ≥35-year-old patients with PD diagnosed within 2 years before screening, Hoehn and Yahr disease stage <3, abnormal dopamine transporter scintigraphy findings confirming dopaminergic nigrostriatal denervation, and stable dopaminergic treatment before enrolment.

The patients were randomly assigned to receive nicotinamide riboside at 500 mg (n=206) or matching placebo (n=204). Treatment was administered orally twice daily for 52 weeks.

The primary outcome was change 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 in MDS-UPDRS were 6.7 and 5.2 points, respectively. The five key secondary outcomes included the individual parts I, II, and III of the MDS-UPDRS, dopamine transporter single-photon emission CT brain imaging findings, and the Non-Motor Symptoms Scale score (NMSS; range, 0–360, with higher scores indicating greater nonmotor symptom burden).

A total of 393 patients (mean age 65.6 years, 34 percent female) were included in the primary analysis. At week 52, the total MDS-UPDRS score increased by 2.45 points with nicotinamide riboside and decreased by 0.27 points with placebo, with an adjusted mean difference of 2.72 points (95 percent confidence interval [CI], 0.47–4.98; p=0.02) favouring placebo.

Of the five key secondary outcomes, four did not significantly differ between the two treatment groups. Meanwhile, nonmotor symptom burden further increased with nicotinamide riboside vs placebo, with an adjusted mean difference in NMSS score of 4.22 points (95 percent CI, 1.07–7.37; p=0.009).

Serious adverse events occurred in 8.3 percent of patients in the nicotinamide riboside group vs 14.1 percent in the placebo group.