Asthma
Conditions
Keywords
Asthma, Avandia
Brief summary
Asthma is a common chronic disease characterized by airway inflammation and bronchoconstriction. This study utilizes the drug rosiglitazone (Avandia)to treat the effects of airway inflammation in patients with asthma. The study will be conducted on 14 adult steroid naive patients with asthma. Patients with qualifying pulmonary function testing values will be eligible for enrollment. Enrolled subjects will be treated with rosiglitazone orally at 2mg dose for 4 weeks. Patients will be reassessed and dosing will increase in 4 week increments up to 8mg.
Detailed description
The current standard-of-care utilizes corticosteroids to down-regulate the inflammatory state in patients with asthma. However, corticosteroids have many side effects and are not universally effective. New safe anti-inflammatory agents are needed to help modulate the disease. Peroxisome proliferator-activated receptor agonists are widely used to manage diabetes mellitus, another common chronic disease. These agents have been study models and have been shown to have anti-inflammatory effects in lung tissue. Case reports have noted improvement in asthma symptoms in patients being treated with these agents. These agents are ideally placed for human research given their long record of safe use in the treatment of type 2 diabetes.
Interventions
DRUGrosiglitazone
2mg, 4mg, 8mg
Sponsors
Creighton University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Able to comprehend and grant a witnessed, written informed consent * Must be greater than 19 years old * Must be able to swallow a tablet * Female participants must have a negative urine pregnancy test at visit 1 and throughout duration of the study * Must have a history of physician diagnosed asthma * Must have a baseline FEV1 \>60% predicted * Must be able to perform pulmonary function testing * Must have methacholine-induced decrease in FEV1 of 20% * Must be capable of withholding medications that may affect the methacholine challenge test * Must be able to withstand a 30 day washout period for all inhaled corticosteroids * Must be able to attend all office visits, 4 weeks apart for 12 weeks. Each visit will last approximately 2-3 hours
Exclusion criteria
* Age 18 or younger * FEV1 \<60% predicted value * History or presence of significant renal, hepatic,neurologic, cardiovascular, hematologic, cerebrovascular, respiratory, endocrine, gastrointestinal, or collagen vascular disorder that in the Investigator's opinion could interfere with the study or require medical attention that would interfere with the study. * History of cancer other than basal cell skin cancer * History of hypoglycemia * Current smokers, greater than 10 pack year history, or patients quitting less than 1 year prior to screening * History within the past year of excessive alcohol intake or drug addiction * History of respiratory infection requiring treatment with an antibiotic within 2 week prior to visit 1 * Chronic intermittent use of inhaled, oral, intra-muscular, topical or intravenous corticosteroids within 4 weeks of visit 1 * Inability to perform consistent spirometry or nitric oxide exhalation * Treatment with an experimental, non-approved drug, or investigational drug within the past 30 days * Known hypersensitivity to rosiglitazone * History of noncompliance to medical regimens and participants who are considered to be potentially unreliable
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Methacholine Responsiveness as Assessed by PC20, | patients were assessed at baseline and at 12 weeks | PC20 is the concentration of methacholine at which patients had a decrease in Forced Expiratory Volume in one second (FEV1) of 20% |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Exhaled Nitric Oxide in Parts Per Billion (Ppb), Parts Per Billion | patients were assessed at baseline and 12 weeks | Fraction Exhaled Nitric oxide was measured on each visit prior to bronchoprovocation by chemiluminescence using an analyzer. |
| Forced Expiratory Volume in 1 Second (FEV1) | patients were assessed at baseline and 12 weeks | FEV1 in liters |
| Forced Expiratory Volume in One Second (FEV1) Percent Predicted | patients were assessed at baseline and 12 weeks | Spirometry was performed on each visit according to American Thoracic Society guidelines. FEV1 percent predicted was measured. |
Countries
United States
Participant flow
Recruitment details
Recruitment was through pulmonary and allergy/immunology clinics from September 2008 to November 2009.
Pre-assignment details
32 patients assessed for eligibility. 16 did not meet inclusion criteria. None of the 16 participants allocated to treatment were excluded before the study began.
Participants by arm
| Arm | Count |
|---|---|
| Rosiglitazone Subjects will take rosiglitazone 2 mg for 4 weeks, then 4mg for 4 weeks, then 8 mg for 4 weeks | 16 |
| Total | 16 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Protocol Violation | 1 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Rosiglitazone |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 16 Participants |
| Age Continuous | 34 years STANDARD_DEVIATION 24 |
| Region of Enrollment United States | 16 participants |
| Sex: Female, Male Female | 10 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 |
Outcome results
Primary
Methacholine Responsiveness as Assessed by PC20,
PC20 is the concentration of methacholine at which patients had a decrease in Forced Expiratory Volume in one second (FEV1) of 20%
Time frame: patients were assessed at baseline and at 12 weeks
Population: 3 subjects were not included in the final analysis due to missing data. Two subjects withdrew by visit 3. 1 had missing data at visit 2 due to equipment failure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rosiglitazone | Methacholine Responsiveness as Assessed by PC20, | Baseline | 3.27 mg/mL | Standard Deviation 2.34 |
| Rosiglitazone | Methacholine Responsiveness as Assessed by PC20, | Week 12 | 8.71 mg/mL | Standard Deviation 7.77 |
p-value: 0.048ANOVA
Secondary
Exhaled Nitric Oxide in Parts Per Billion (Ppb), Parts Per Billion
Fraction Exhaled Nitric oxide was measured on each visit prior to bronchoprovocation by chemiluminescence using an analyzer.
Time frame: patients were assessed at baseline and 12 weeks
Population: 2 patients withdrew from the study in visit 3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rosiglitazone | Exhaled Nitric Oxide in Parts Per Billion (Ppb), Parts Per Billion | Baseline | 48 parts per billion | Standard Deviation 32 |
| Rosiglitazone | Exhaled Nitric Oxide in Parts Per Billion (Ppb), Parts Per Billion | 12 weeks | 41 parts per billion | Standard Deviation 35 |
p-value: 0.183Friedman
Secondary
Forced Expiratory Volume in 1 Second (FEV1)
FEV1 in liters
Time frame: patients were assessed at baseline and 12 weeks
Population: Two subjects withdrew from the study in visit 3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rosiglitazone | Forced Expiratory Volume in 1 Second (FEV1) | Baseline | 2.95 Liters | Standard Deviation 0.89 |
| Rosiglitazone | Forced Expiratory Volume in 1 Second (FEV1) | Week 12 | 3.04 Liters | Standard Deviation 0.95 |
p-value: 0.398Friedman
Secondary
Forced Expiratory Volume in One Second (FEV1) Percent Predicted
Spirometry was performed on each visit according to American Thoracic Society guidelines. FEV1 percent predicted was measured.
Time frame: patients were assessed at baseline and 12 weeks
Population: Two subjects withdrew from the study in visit 3
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Rosiglitazone | Forced Expiratory Volume in One Second (FEV1) Percent Predicted | Baseline | 82 percent predicted | Standard Deviation 12 |
| Rosiglitazone | Forced Expiratory Volume in One Second (FEV1) Percent Predicted | Week 12 | 85 percent predicted | Standard Deviation 15 |