In models of dopaminergic neuronal loss, the dopamine agonist pramipexole has exhibited neuroprotective properties. The Pramipexole On Underlying Disease (PROUD) study was designed to identify whether early versus delayed pramipexole initiation has clinical and neuroimaging benefits in patients with Parkinson's disease (PD). Of 535 patients, 261 were randomly assigned to receive pramipexole and 274 to receive placebo. The primary endpoint was the 15-month change from baseline in total score on the unified Parkinson’s disease rating scale (UPDRS). At 15 months (n=411), adjusted mean change in UPDRS total score showed no significant difference between early and delayed pramipexole (−0•4 points, 95% CI −2•2 to 1•4, p=0•65).
An accompanying editorial discusses the delayed-start study design. Delayed-start studies are designed to assess disease modification while avoiding the confounding of symptomatic effects. Patients entering the trial are randomly assigned either to receive active drug for the entire study (i.e. early start) or to receive placebo for period 1 and active drug for period 2 (i.e. delayed start). Assuming period 2 is sufficiently long, both groups should experience the full symptomatic benefit of the treatment and any difference at the end of the trial should be attributable to disease modification that accrued to the early-start group in period 1 and was not available to the delayed-start group. The author of the editorial stated that the study was a well executed trial but delayed-start studies can only provide a signal of disease modification; long-term trials are necessary to define the scope and magnitude of the clinical benefit. This study demonstrated no slowing of disease progression with pramipexole.