Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial
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...
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Published: |
Public Library of Science
2016
|
| Online Access: | https://eprints.nottingham.ac.uk/37796/ |
| _version_ | 1848795536380919808 |
|---|---|
| author | Leroyer, Christophe Anderson, J.R. Mortimer, K. Pang, L. Smith, K.M. Bailey, H. Hodgson, D.B. Shaw, Dominick E. Knox, A.J. Harrison, Timothy W. |
| author_facet | Leroyer, Christophe Anderson, J.R. Mortimer, K. Pang, L. Smith, K.M. Bailey, H. Hodgson, D.B. Shaw, Dominick E. Knox, A.J. Harrison, Timothy W. |
| author_sort | Leroyer, Christophe |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | 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. |
| first_indexed | 2025-11-14T19:33:39Z |
| format | Article |
| id | nottingham-37796 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:33:39Z |
| publishDate | 2016 |
| publisher | Public Library of Science |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-377962020-05-04T18:05:47Z https://eprints.nottingham.ac.uk/37796/ Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial Leroyer, Christophe Anderson, J.R. Mortimer, K. Pang, L. Smith, K.M. Bailey, H. Hodgson, D.B. Shaw, Dominick E. Knox, A.J. Harrison, Timothy W. 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. Public Library of Science 2016-08-25 Article PeerReviewed Leroyer, Christophe, Anderson, J.R., Mortimer, K., Pang, L., Smith, K.M., Bailey, H., Hodgson, D.B., Shaw, Dominick E., 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 http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0160257 doi:10.1371/journal.pone.0160257 doi:10.1371/journal.pone.0160257 |
| spellingShingle | Leroyer, Christophe Anderson, J.R. Mortimer, K. Pang, L. Smith, K.M. Bailey, H. Hodgson, D.B. Shaw, Dominick E. Knox, A.J. Harrison, Timothy W. Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial |
| title | Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial |
| title_full | Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial |
| title_fullStr | Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial |
| title_full_unstemmed | Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial |
| title_short | Evaluation of the PPAR-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial |
| title_sort | evaluation of the ppar-γ agonist pioglitazone in mild asthma: a double-blind randomized controlled trial |
| url | https://eprints.nottingham.ac.uk/37796/ https://eprints.nottingham.ac.uk/37796/ https://eprints.nottingham.ac.uk/37796/ |