Caffeine as symptomatic treatment for Parkinson disease (Café-PD): A randomized trial

Abstract

Objective: To assess effects of caffeine on Parkinson disease (PD).

Methods: In this multicenter parallel-group controlled trial, patients with PD with 1-8 years disease duration, Hoehn & Yahr stages I-III, on stable symptomatic therapy were randomized to caffeine 200 mg BID vs matching placebo capsules for 6-18 months. The primary research question was whether objective motor scores would differ at 6 months (Movement Disorder Society-sponsored Unified Parkinson's Disease Rating Scale [MDS-UPDRS]-III, Class I evidence). Secondary outcomes included safety and tolerability, motor symptoms (MDS-UPDRS-II), motor fluctuations, sleep, nonmotor symptoms (MDS-UPDRS-I), cognition (Montreal Cognitive Assessment), and quality of life.

Results: Sixty patients received caffeine and 61 placebo. Caffeine was well-tolerated with similar prevalence of side effects as placebo. There was no improvement in motor parkinsonism (the primary outcome) with caffeine treatment compared to placebo (difference between groups -0.48 [95% confidence interval -3.21 to 2.25] points on MDS-UPDRS-III). Similarly, on secondary outcomes, there was no change in motor signs or motor symptoms (MDS-UPDRS-II) at any time point, and no difference on quality of life. There was a slight improvement in somnolence over the first 6 months, which attenuated over time. There was a slight increase in dyskinesia with caffeine (MDS-UPDRS-4.1+4.2 = 0.25 points higher), and caffeine was associated with worse cognitive testing scores (average Montreal Cognitive Assessment = 0.66 [0.01, 1.32] worse than placebo).

Conclusion: Caffeine did not provide clinically important improvement of motor manifestations of PD (Class I evidence). Epidemiologic links between caffeine and lower PD risk do not appear to be explained by symptomatic effects.

Clinicaltrialsgov identifier: NCT01738178.

Classification of evidence: This study provides Class I evidence that for patients with PD, caffeine does not significantly improve motor manifestations.

Figure 1. Patient flow throughout the course of the study

BDI = Beck Depression Inventory.

Figure 2. Change from baseline in selected Parkinson disease measures in caffeine vs placebo

(A) Change in Movement Disorder Society–sponsored Unified Parkinson's Disease Rating Scale (MDS-UPDRS) III, (B) change in MDS-UPDRS 1.8 (daytime sleepiness), (C) change in MDS-UPDRS II, (D) change in Scales for Outcomes in PD (SCOPA) (daytime), (E) change in MDS-UPDRS IV (dyskinesia), (F) change in Montreal Cognitive Assessment. Note that the primary outcome is at 6 months; only a proportion of patients continued follow-up into 12 months (73%) and 18 months (55%). Error bars indicate standard error. The asterisk indicates a statistically significant difference between caffeine and placebo (p < 0.05).