Asthma, Obesity
Conditions
Keywords
Asthma, Adipose Tissue, Asthmatics, Pioglitazone, Actos, Obesity, Exacerbation, Fat, Overweight, Leptin, Adiponectin, Wheezing, Vermont, Pulmonary, Lung
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.
Interventions
DRUGPioglitazone
Pioglitazone tablets; 30 mg/day for 2 weeks; then increased to 45 mg/day until week 12 (approximately 3 months)
DRUGPlacebo
Matching placebo (inert tablet)
Sponsors
American Lung Association
University of Pittsburgh
University of Vermont
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PC20 | 12 weeks | Airway reactivity will be measured with methacholine challenge testing following ATS guidelines. This is the concentration of methacholine that produces a 20% decrease in lung function (measured by forced expiratory volume in 1 second) |
Countries
United States
Participant flow
Pre-assignment details
5 participants did not qualify for randomization as they had a negative methacholine.
Participants by arm
| Arm | Count |
|---|---|
| 1. Pioglitazone Pioglitazone: Pioglitazone tablets; 30 mg/day for 2 weeks; then increased to 45 mg/day until week 12 (approximately 3 months) | 12 |
| 2. Placebo Placebo: Matching placebo (inert tablet) | 11 |
| Total | 23 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | 1. Pioglitazone | 2. Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 11 Participants | 23 Participants |
| PC20 | 1.60 mg/ml STANDARD_DEVIATION 5.91 | 1.99 mg/ml STANDARD_DEVIATION 3.08 | 1.90 mg/ml STANDARD_DEVIATION 3.08 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants | 2 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 8 Participants | 9 Participants | 17 Participants |
| Region of Enrollment United States | 12 participants | 11 participants | 23 participants |
| Sex: Female, Male Female | 7 Participants | 8 Participants | 15 Participants |
| Sex: Female, Male Male | 5 Participants | 3 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 12 | 0 / 11 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 |
Outcome results
Primary
PC20
Airway reactivity will be measured with methacholine challenge testing following ATS guidelines. This is the concentration of methacholine that produces a 20% decrease in lung function (measured by forced expiratory volume in 1 second)
Time frame: 12 weeks
| Arm | Measure | Value (MEDIAN) | Dispersion |
|---|---|---|---|
| 1. Pioglitazone | PC20 | 5.08 mg/ml | Standard Deviation 7.42 |
| 2. Placebo | PC20 | 2.37 mg/ml | Standard Deviation 15.22 |