Pilot Study of Pioglitazone for the Treatment of Moderate to Severe Asthma in Obese Asthmatics

Participants in this study will be randomly assigned (like the flip of a coin) to
pioglitazone or a placebo (an inactive pill). They will be given study medication to take
everyday 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.

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 life-time 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) >400 pg/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 or nutritional supplements (stable dose of calcium, vitamin D, or
multivitamin is OK)

- 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