Peroxisome proliferator-activated receptor gamma (PPAR-gamma): a novel therapeutic target for asthma?

ISRCTN	ISRCTN80109258
DOI	https://doi.org/10.1186/ISRCTN80109258
ClinicalTrials.gov number	NCT01134835
Secondary identifying numbers	33100; EME 08/246/02

Submission date: 29/01/2010
Registration date: 16/04/2010
Last edited: 11/04/2017

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Respiratory

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Tim Harrison
Scientific

University of Nottingham
Respiratory Division
Clinical Sciences Building
Nottingham City Hospital
Nottingham
NG5 1PB
United Kingdom

Phone	+44 (0)115 823 1725
Email	tim.harrison@nottingham.ac.uk

Study information

Study design	Randomised double-blind placebo-controlled two parallel group clinical trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	Peroxisome proliferator-activated receptor gamma (PPAR-gamma): a novel therapeutic target for asthma? A randomised double-blind placebo-controlled clinical trial.
Study objectives	To test the hypothesis that stimulation of peroxisome proliferator-activated receptor gamma (PPAR-gamma) receptors has a therapeutic role in the treatment of asthma. Link to EME project website: http://www.eme.ac.uk/projectfiles/0824602info.pdf Link to protocol: http://www.eme.ac.uk/projectfiles/0824602info.pdf
Ethics approval(s)	Nottingham Research and Ethics Committee 2, 08/08/2008, ref: 08/H0408/120
Health condition(s) or problem(s) studied	Asthma
Intervention	Participants are required for a total of 18 weeks. Follow up and investigation is identical in both arms. The run-in period is 2 weeks. Participants are randomised to either active or placebo arms for 12 weeks: 1. Pioglitazone 30 mg daily by mouth for 4 weeks then 45 mg daily for 8 weeks 2. Placebo 30 mg daily by mouth for 4 weeks then 45 mg daily for 8 weeks The participants are followed up at weeks 4, 8 and 12. A final observation visit occurs at week 16 when the participants are no longer taking the IMP.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Pioglitazone
Primary outcome measure	FEV1 after 12 weeks
Secondary outcome measures	Change over 12 weeks in: 1. Daily asthma symptoms 2. Mean morning and evening peak flow 3. Juniper asthma control questionnaire and asthma quality of life scores 4. Exhaled nitric oxide level 5. Bronchial hyper-responsiveness 6. Induced sputum cell counts 7. Mechanistic analysis. This includes assay of histone acetyltransferase (HAT) and histone deacetylase (HDAC) levels, PPAR-gamma activation and measurement of chemokines (eotaxin, monocyte chemotactic protein-1 [MCP-1], IP10), growth factors (vascular endothelial growth factor [VEGF]) and effector mediators (cyst-leukotrienes, histamine and eosinophilic cationic protein).
Overall study start date	01/01/2010
Completion date	01/01/2012

Eligibility

Participant type(s)	Patient
Age group	Adult
Lower age limit	18 Years
Sex	Both
Target number of participants	100
Key inclusion criteria	1. Aged 18 - 75 years, of either sex, with a clinical diagnosis of asthma 2. Forced expiratory volume in one second (FEV1) greater than or equal to 60% predicted and an increase in forced expiratory volume in one second (FEV1) of greater than 12% following inhaled salbutamol 400 µg or peak flow variability greater than 12% during run in 3. Permitted medication, 0 - 800 µg inhaled beclomethasone diproprionate or equivalent and a short acting beta-2-agonist as required
Key exclusion criteria	1. Inability to produce a sputum sample on induction 2. Currently smoking 3. Greater than 10 pack years smoking history 4. Treatment with leukotriene antagonists 5. Long-acting beta agonists or theophylline 6. Liver or cardiovascular disease 7. Oral steroid treatment or exacerbation within 6 weeks 8. Females who are pregnant, lactating or not using adequate contraception 9. Any contra-indication to pioglitazone (hypersensitivity to pioglitazone, cardiac failure, history of cardiac failure, hepatic impairment, diabetic ketoacidosis) 10. Oral or insulin treatment for diabetes 11. Treatment with gemfibrozol or rifampicin
Date of first enrolment	01/01/2010
Date of final enrolment	01/01/2012

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

University of Nottingham

Nottingham
NG5 1PB
United Kingdom

Sponsor information

University of Nottingham (UK)
University/education

c/o Paul Cartledge
Research Innovation Services
King's Meadow Campus
Lenton Lane
Nottingham
NG7 2NR
England
United Kingdom

Phone	+44 (0)115 951 5679
Email	paul.cartledge@nottingham.ac.uk
Website	http://www.nottingham.ac.uk/
"ROR"	https://ror.org/01ee9ar58

Funders

Funder type

Government

Medical Research Council
Government organisation / National government

Alternative name(s): Medical Research Council (United Kingdom), UK Medical Research Council, MRC
Location: United Kingdom

Nottingham Respiratory Biomedical Research Unit (UK)

No information available

Efficacy and Mechanism Evaluation Programme
Government organisation / National government

Alternative name(s): NIHR Efficacy and Mechanism Evaluation Programme, EME
Location: United Kingdom

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Results article	results	25/08/2016		Yes	No

Editorial Notes

11/04/2017: Publication reference added.