Asthma
Conditions
Keywords
Asthma, obesity, exacerbation, asthmatics, fat, overweight, adipose tissue, leptin, adiponectin, pioglitazone, Actos, wheezing, Pittsburgh, Pennsylvania, 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 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.
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
Takeda
University of Vermont
Fernando Holguin
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 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| FEV1 % Predicted | 12 weeks | — |
| 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 |
| Exhaled Nitric Oxide Ppb | 12 weeks | — |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pioglitazone pioglitazone: pioglitazone tablets: 30 mg/day for 2 weeks; then increased to 45 mg/day until week 12 (approximately 3 months) | 12 |
| 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 | Total | Pioglitazone | Placebo |
|---|---|---|---|
| Age asthma onset | 18 years STANDARD_DEVIATION 14.95 | 15 years STANDARD_DEVIATION 11 | 21 years STANDARD_DEVIATION 18.9 |
| 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 | 23 Participants | 12 Participants | 11 Participants |
| Age, Continuous | 40.2 years STANDARD_DEVIATION 12.05 | 39.4 years STANDARD_DEVIATION 10 | 41 years STANDARD_DEVIATION 14.1 |
| Asthma exacerbation in last 12 months No reported exacerbation | 10 participants | 6 participants | 4 participants |
| Asthma exacerbation in last 12 months Reported an exacerbation | 13 participants | 6 participants | 7 participants |
| Body Mass Index | 41.15 kg/m^2 STANDARD_DEVIATION 7.3 | 38.8 kg/m^2 STANDARD_DEVIATION 6.8 | 43.5 kg/m^2 STANDARD_DEVIATION 7.8 |
| Depression Participants reporting Depression | 13 participants | 7 participants | 6 participants |
| Depression Participants without Depression | 10 participants | 5 participants | 5 participants |
| Exhaled Nitric Oxide | 29.2 ppb STANDARD_DEVIATION 28.1 | 27.6 ppb STANDARD_DEVIATION 27.8 | 30.8 ppb STANDARD_DEVIATION 28.4 |
| FEV1/FVC (% predicted after bronchodilator use) | 94.35 % predicted STANDARD_DEVIATION 19.51 | 90.9 % predicted STANDARD_DEVIATION 31.2 | 97.8 % predicted STANDARD_DEVIATION 7.82 |
| FEV1/FVC (% predicted before bronchodilator use) | 95.1 % predicted STANDARD_DEVIATION 11.16 | 95.3 % predicted STANDARD_DEVIATION 11.2 | 94.9 % predicted STANDARD_DEVIATION 11.12 |
| FEV1 (% predicted after bronchodilator use) | 82.7 % predicted STANDARD_DEVIATION 14.85 | 77.3 % predicted STANDARD_DEVIATION 25.1 | 88.1 % predicted STANDARD_DEVIATION 4.6 |
| FEV1 (% predicted before bronchodilator use) | 81.9 % predicted STANDARD_DEVIATION 13.65 | 82.3 % predicted STANDARD_DEVIATION 12.1 | 81.5 % predicted STANDARD_DEVIATION 15.2 |
| FVC (% predicted after bronchodilator use) | 83.9 % predicted STANDARD_DEVIATION 21.95 | 79.5 % predicted STANDARD_DEVIATION 27.6 | 88.3 % predicted STANDARD_DEVIATION 16.3 |
| FVC (% predicted before bronchodilator use) | 86.05 % predicted STANDARD_DEVIATION 14.95 | 86.8 % predicted STANDARD_DEVIATION 13.7 | 85.3 % predicted STANDARD_DEVIATION 16.2 |
| Gastroesophageal Reflux Disease (GERD) Participants with GERD | 12 participants | 7 participants | 5 participants |
| Gastroesophageal Reflux Disease (GERD) Participants without GERD | 11 participants | 5 participants | 6 participants |
| Immunoglobulin E | 433.1 IU/ml STANDARD_DEVIATION 428.95 | 291.2 IU/ml STANDARD_DEVIATION 313.2 | 575 IU/ml STANDARD_DEVIATION 544.7 |
| Inhaled corticosteroid High dose | 9 participants | 4 participants | 5 participants |
| Inhaled corticosteroid Low dose | 2 participants | 0 participants | 2 participants |
| Inhaled corticosteroid Medium dose | 12 participants | 8 participants | 4 participants |
| Juniper Asthma Control | 2.115 scores on a scale STANDARD_DEVIATION 0.965 | 1.75 scores on a scale STANDARD_DEVIATION 0.63 | 2.48 scores on a scale STANDARD_DEVIATION 1.3 |
| Long acting beta agonist Did not use long acting beta agonist | 4 participants | 2 participants | 2 participants |
| Long acting beta agonist Used long acting beta agonist | 19 participants | 10 participants | 9 participants |
| Oral steroids in last 12 months Did not use oral steroids | 12 participants | 5 participants | 7 participants |
| Oral steroids in last 12 months Used oral steroids | 11 participants | 7 participants | 4 participants |
| 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 | 6 Participants | 4 Participants | 2 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 | 17 Participants | 8 Participants | 9 Participants |
| Region of Enrollment United States | 23 participants | 12 participants | 11 participants |
| Seasonal allergies Non-allergic | 3 participants | 2 participants | 1 participants |
| Seasonal allergies Reported allergies | 20 participants | 10 participants | 10 participants |
| Sex: Female, Male Female | 15 Participants | 7 Participants | 8 Participants |
| Sex: Female, Male Male | 8 Participants | 5 Participants | 3 Participants |
| Short acting beta agonist Did not use short acting beta agonist | 1 participants | 1 participants | 0 participants |
| Short acting beta agonist Used short acting beta agonist | 22 participants | 11 participants | 11 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 12 / 12 | 11 / 11 |
| serious Total, serious adverse events | 0 / 12 | 0 / 11 |
Outcome results
Primary
Airway Reactivity
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.
Time frame: 12 weeks
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Pioglitazone | Airway Reactivity | 5.08 mg/ml |
| Placebo | Airway Reactivity | 2.37 mg/ml |
Secondary
Exhaled Nitric Oxide Ppb
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | Exhaled Nitric Oxide Ppb | 27.6 ppb | Standard Deviation 27.8 |
| Placebo | Exhaled Nitric Oxide Ppb | 30.8 ppb | Standard Deviation 28.4 |
Secondary
FEV1 % Predicted
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | FEV1 % Predicted | 80.3 % predicted | Standard Deviation 15 |
| Placebo | FEV1 % Predicted | 85.2 % predicted | Standard Deviation 12 |
Secondary
Juniper Asthma Control Questionnaire
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
Time frame: 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Pioglitazone | Juniper Asthma Control Questionnaire | 1.62 Scores on a scale | Standard Deviation 0.6 |
| Placebo | Juniper Asthma Control Questionnaire | 1.82 Scores on a scale | Standard Deviation 1 |