NOPARK: nicotinamide riboside did not help early Parkinson disease and scored worse than placebo

Design

Phase 3, randomised, double-blind, placebo-controlled, 11 centres in Norway

Population

393 analysed adults with early Parkinson disease (diagnosed within 2 years)

Primary outcome

Change in MDS-UPDRS total score (parts I to III) at 52 weeks

Effect

Adjusted mean difference 2.72 points (95% CI 0.47 to 4.98), favouring placebo; non-motor score difference 4.22 (1.07 to 7.37)

NOPARK was a randomised, double-blind, placebo-controlled phase 3 trial at 11 centres in Norway. It enrolled people aged 35 or over with Parkinson disease diagnosed within 2 years, Hoehn and Yahr stage below 3 and abnormal dopamine transporter imaging, on stable dopaminergic treatment. Of 410 randomised, 393 were analysed. They received nicotinamide riboside 500 mg twice daily or placebo for 52 weeks.

The MDS-UPDRS total score (parts I to III) rose by 2.45 points with nicotinamide riboside and fell by 0.27 with placebo, an adjusted difference of 2.72 points (95% CI 0.47 to 4.98; P=0.02) favouring placebo. Four of five key secondary outcomes did not differ, but non-motor symptom burden worsened more with nicotinamide riboside (4.22 points, 1.07 to 7.37).

The 2.72-point difference sits below the trial's stated thresholds for a clinically important change (5.2 points for worsening), so the harm signal is modest. The clear message is absence of benefit.

• Patients asking about this supplement can be told that a 52-week phase 3 trial found no improvement and slightly worse scores.
• Ask patients with Parkinson disease about supplements and over-the-counter products at each review.
• Do not offer nicotinamide riboside as disease-modifying therapy; the authors state the findings do not support it.
• Non-motor symptoms were worse in the supplement group, so enquire about them if a patient has been taking it.

Why it matters

It is a reminder that a plausible mechanism and promising early data do not guarantee benefit in a properly powered trial.

Don't overread it

A modest difference favouring placebo is more likely to show no effect than to show real harm, and the trial ran for 52 weeks in people with early disease.

The statistics, in plain English

The difference of 2.72 points has an interval of 0.47 to 4.98, so it only just excludes zero. The trial's own thresholds for a clinically important worsening was 5.2 points, so the statistically significant gap is smaller than what would matter to a patient.

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