A randomized pilot clinical trial of the safety of pioglitazone in treatment of patients with Alzheimer disease
Year of Publication 2011
Abstract
Objectives: To evaluate the safety of the peroxisome proliferator-activated receptor gamma agonist pioglitazone in nondiabetic patients with Alzheimer disease (AD) and to explore treatment effect sizes on clinical outcomes.; Design: Double-blind, placebo-controlled randomized controlled trial of 18-month duration.; Setting: Two academic medical center outpatient clinics.; Patients: Nondiabetic patients meeting research criteria for probable AD were enrolled. Twenty-five of 29 subjects completed the study; no withdrawals were attributable to adverse effects.; Intervention: Subjects received pioglitazone (Actos), titrated to 45 mg daily, or matching placebo, and 200 IU of vitamin E daily. Patients maintained treatment with cholinesterase inhibitors and could begin memantine therapy when it became available during the study.; Main Outcome Measures: The primary outcome was frequency of reported adverse effects (AEs). Secondary outcomes were measures of cognition, activities of daily living, neuropsychiatric symptoms, and global function.; Results: Peripheral edema was the principal AE occurring more frequently in subjects taking pioglitazone than placebo (28.6% vs 0%). This is consistent with the known AE profile of pioglitazone. No group differences in laboratory measures were identified. No significant treatment effect was observed on exploratory analysis of clinical efficacy.; Conclusions: Pioglitazone was generally well tolerated in this pilot study. There were no serious or unanticipated adverse events or clinical laboratory changes attributable to pioglitazone over a long-term exposure in nondiabetic patients with AD. The tolerability of pioglitazone in this population and peroxisome proliferator-activated receptor gamma effects in laboratory models of AD support further study of this drug class in earlier disease stages.; Trial Registration: clinicaltrials.gov Identifier: NCT00982202.;