Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial

Leroyer, Christophe and Anderson, J.R. and Mortimer, K. and Pang, L. and Smith, K.M. and Bailey, H. and Hodgson, D.B. and Shaw, Dominick E. and Knox, A.J. and Harrison, Timothy W. (2016) Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial. PLoS ONE, 11 (8). e0160257. ISSN 1932-6203

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Abstract

Background

Peroxisome proliferator-activated receptor gamma (PPAR-γ) is a nuclear receptor that modulates inflammation in models of asthma. To determine whether pioglitazone improves measures of asthma control and airway inflammation, we performed a single-center randomized, double-blind, placebo-controlled, parallel-group trial.

Methods

Sixty-eight participants with mild asthma were randomized to 12 weeks pioglitazone (30 mg for 4 weeks, then 45 mg for 8 weeks) or placebo. The primary outcome was the adjusted mean forced expiratory volume in one second (FEV1) at 12 weeks. The secondary outcomes were mean peak expiratory flow (PEF), scores on the Juniper Asthma Control Questionnaire (ACQ) and Asthma Quality of Life Questionnaire (AQLQ), fractional exhaled nitric oxide (FeNO), bronchial hyperresponsiveness (PD20), induced sputum counts, and sputum supernatant interferon gamma-inducible protein-10 (IP-10), vascular endothelial growth factor (VEGF), monocyte chemotactic protein-1 (MCP-1), and eosinophil cationic protein (ECP) levels. Study recruitment was closed early after considering the European Medicines Agency’s reports of a potential increased risk of bladder cancer with pioglitazone treatment. Fifty-five cases were included in the full analysis (FA) and 52 in the per-protocol (PP) analysis.

Results

There was no difference in the adjusted FEV1 at 12 weeks (-0.014 L, 95% confidence interval [CI] -0.15 to 0.12, p = 0.84) or in any of the secondary outcomes in the FA. The PP analysis replicated the FA, with the exception of a lower evening PEF in the pioglitazone group (-21 L/min, 95% CI -39 to -4, p = 0.02).

Conclusions

We found no evidence that treatment with 12 weeks of pioglitazone improved asthma control or airway inflammation in mild asthma.

Item Type: Article
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Respiratory Medicine
Identification Number: https://doi.org/10.1371/journal.pone.0160257
Depositing User: Eprints, Support
Date Deposited: 20 Oct 2016 13:34
Last Modified: 27 Jan 2017 19:25
URI: http://eprints.nottingham.ac.uk/id/eprint/37796

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