Research in context
Evidence before this study
We searched PubMed for articles published in English before Jan 15, 2015, using the terms “Parkinson's disease”, “disease modification”, “clinical trials”, and “pioglitazone”. As of that date, no agents had proven to be disease-modifying agents (ie, to slow progression) in patients with Parkinson's disease and no studies had assessed the potential disease-modifying effects of pioglitazone.
Added value of this study
This is the first randomised controlled trial of pioglitazone, a peroxisome proliferator-activated receptor γ agonist, as a potential disease-modifying agent in patients with Parkinson's disease. The rationale for the choice of study agent was based on the robust preclinical data showing a neuroprotective effect in animal models at the doses approved for use in human beings. Although the findings of this trial do not warrant further testing of pioglitazone in patients with Parkinson's disease, the design of our study could guide that of other studies, as we have shown that this design is useful and efficient to exclude a compound unlikely to be successful in larger and more costly phase 3 trials.
Implications of all available evidence
These findings suggest that pioglitazone at the doses studied here is unlikely to modify progression in early Parkinson's disease. Further study of pioglitazone in a larger trial in Parkinson's disease is not recommended, although other peroxisome proliferator-activated receptor γ agonists might deserve further exploration as disease-modifying agents in Parkinson's disease.