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

Phase 2

Completed

Conditions: Asthma

Interventions: Drug: placebo
Drug: pioglitazone

Registration Number: NCT00634036

Lead Sponsor: Fernando Holguin

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 body can cause higher-than-normal levels of leptin and lower-than-normal 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 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 23

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
2	placebo	-
1	pioglitazone	-

Primary Outcome Measures

Name	Time	Method
Airway Reactivity	12 weeks	Presence and degree of airway hyperresponsiveness assessed by methacholine challenge test. PC20= Methacholine dose at wich the FEV1 deops by \> 20% from pre-methacholine baseline values.

Secondary Outcome Measures

Name	Time	Method
Juniper Asthma Control Questionnaire	12 weeks	The Juniper Asthma Control Questionnaire is a validated scale ranging from 0 to 6. Higher scores represent poorer asthma control. Values \> 1.5 are compatible with poorly controlled asthma
FEV1 % Predicted	12 weeks
Exhaled Nitric Oxide Ppb	12 weeks