Clinical trial NCT00787644: Pilot Study of Pioglitazone for the Treatment of Moderate to Severe Asthma in Obese Asthmatics (Glitz Asthma)
Official title: A Randomized, Placebo-Controlled Pilot Study of Pioglitazone for the Treatment of Moderate to Severe Asthma in Obese Asthmatics. (The GLITZ Asthma Study)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Asthma
Obesity
Keywords: Asthma
Adipose Tissue
Asthmatics
Pioglitazone
Actos
Obesity
Exacerbation
Fat
Overweight
Leptin
Adiponectin
Wheezing
Vermont
Pulmonary
Lung
Lead sponsor: University of Vermont
Sponsor class: OTHER
Collaborators: name: American Lung Association
name: University of Pittsburgh
First posted: 2008-11-07
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Asthmatics who are significantly overweight tend to have more severe symptoms, more flare ups, and are more likely to have poorly-controlled asthma when compared to other asthmatics.

Researchers believe this occurs because excess adipose tissue (fat) in the bosy can cause higher-than-normal levels of leptin and lower levels of adiponectin in the blood.

The researchers of this study are testing a medication called pioglitazone in overweight asthmatics because they believe it can help regulate leptin and adiponectin and that this may improve symptoms of asthma.

Detailed description: Participants in this study will be randomly assigned (like the flip of a coin) to pioglitazone or placebo (an inactive pill). They will be given study medication to take every day for 12 weeks (3 months).

Participants will complete a number of asthma-related questionnaires and a variety of pulmonary function tests. Participants will undergo physical exams, an electrocardiogram, and blood sampling to measure leptin, adiponectin, markers of inflammation, blood cell counts, glucose levels, BNP hormone levels, and liver function.

To monitor participants throughout the study, follow-up visits will be done at 2, 6, and 12 weeks after starting study drug. At these visits many of the pulmonary function tests and questionnaires will be repeated.

Eligibility criteria: Inclusion Criteria:

* Asthma diagnosed by a physician at least 1 year prior to study enrollment
* Poorly-controlled asthma at study enrollment
* Non smokers (stopped smoking at least 1 year ago) and limited lifetime history of smoking
* Body mass index 30-60
* Responds to methacholine challenge test with PC20 of \<16 mg/ml
* On a stable dose of inhaled corticosteroid for at least 4 weeks prior to study entry
* FEV1 \> 60% predicted
* Able to obtain weekly weights at home

Exclusion Criteria:

* Systemic steroids within the past 4 weeks
* Lung pathology other than asthma
* Other significant non-pulmonary co-morbidities such as: coronary artery disease, peripheral vascular disease, cerebrovascular disease, congestive heart failure with an ejection fraction \<50%, liver disease or elevated liver enzymes at baseline, malignancy (excluding non-melanoma skin cancers), AIDS, renal failure with serum creatinine \>3.0, or disorders requiring steroid treatment such as vasculitis, lupus, rheumatoid arthritis
* B-type natriuretic peptide (BNP) \>400pg/ml
* Pregnant or lactating
* Currently taking a beta blocker, a CYP2C8 inhibitor or inducer such as gemfibrozil or rifampin, a TZD (thiazolidinedione), or allergic to TZD
* Taking antioxidants (if taking a multivitamin must be on a stable regimen prior to enrollment)
* Illicit drug use within the past year
* Current/active upper respiratory infection (if active URI, wait until asymptomatic for 1 week to enroll)
* Asthma exacerbation within the past 4 weeks (includes ER, urgent care, or hospital visits due to asthma resulting in an increase in asthma-related medications)
* Undergoing evaluation for sleep apnea, or plans to institute treatment for sleep apnea (patients on a stable treatment regimen for sleep apnea for the last 3 months will be allowed to participate)
* Clinically significant abnormalities present on screening 12-lead electrocardiogram
* Women of childbearing potential using oral contraceptives who are not willing to use a second method of contraception during the study

Primary outcomes:
measure: PC20
timeFrame: 12 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Colchester
country: United States
facility: The Vermont Lung Center at the University of Vermont
state: Vermont
Study officials:
affiliation: The Vermont Lung Center at the University of Vermont
name: Anne E Dixon, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Hashimoto Y, Nakahara K. Improvement of asthma after administration of pioglitazone. Diabetes Care. 2002 Feb;25(2):401. doi: 10.2337/diacare.25.2.401. No abstract available.
citation: Lee KS, Kim SR, Park SJ, Park HS, Min KH, Jin SM, Lee MK, Kim UH, Lee YC. Peroxisome proliferator activated receptor-gamma modulates reactive oxygen species generation and activation of nuclear factor-kappaB and hypoxia-inducible factor 1alpha in allergic airway disease of mice. J Allergy Clin Immunol. 2006 Jul;118(1):120-7. doi: 10.1016/j.jaci.2006.03.021. Epub 2006 May 19.