Official Title: “The Effects of the PPARy Agonist Rosiglitazone on Airway Hyperreactivity”

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 12mg.

Study Type: Interventional

Study Design: Treatment, Non-Randomized, Open Label, Active Control, Single Group Assignment, Safety/Efficacy Study

Study Primary Completion Date: August 2009

The current standard-of-care utilizes corticosteroids to down-regulate the inflammatory state in patients with asthma. However, corticosteroids have many side effects are 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 studies in 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.

Intervention(s) in this Clinical Trial

• Drug: rosiglitazone
  • Each patient will take 2mg rosiglitazone daily.
• Drug: rosiglitazone
  • Each patient will take 4mg rosiglitazone daily.
• Drug: rosiglitazone
  • Each patient will take 8mg rosiglitazone daily.

Arms, Groups and Cohorts in this Clinical Trial

• Active Comparator: 1
  • Each patient will take 2mg rosiglitazone daily. Outcome measurements will be taken after 4 weeks of treatment and dose will be increased.
• Active Comparator: 2
  • Each patient will take 4mg rosiglitazone daily. Outcome measurements will be taken after 4 weeks and dosage will be increased.
• Active Comparator: 3
  • Each patient will take 8mg rosiglitazone daily. Outcome measurements will be taken after 4 weeks and medication will be stopped. No further testing.

Primary Measures

• To examine whether rosiglitazone changes airway hyperreactivity in steroid naive asthmatics by measuring methacholine responsiveness
  • Time Frame: patients are assessed every 4 weeks for a 12 week period
    Safety Issue?: No

Secondary Measures

• To examine whether rosiglitazone changes inflammation in asthmatics by measuring the level of exhaled nitric oxide
  • Time Frame: patients will be reassessed every 4 weeks for a 12 week period
    Safety Issue?: No
• To examine whether or not it changes pulmonary function in asthmatics by measuring spirometry and impulse oscillometry.
  • Time Frame: patients will be reassessed every 4 weeks for a 12 week period
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 19 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: Creighton University

Overall Clinical Trial Officials and Contacts

Tammy Wichman, MD Principal Investigator Creighton University Medical Center  

Overall Contact: Amy Keyes, RRT 402-449-4533 amy.keyes@creighton.edu

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00614874

Study ID Number: 07-14592

ClinicalTrials.gov Identifier: NCT00614874

Health Authority: United States: Institutional Review Board