The Use of Rosiglitazone to Treat Asthma - Full Text View

Sponsor:	Creighton University
Information provided by (Responsible Party):	Tammy Wichman, Creighton University
ClinicalTrials.gov Identifier:	NCT00614874

Purpose

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.

Condition	Intervention	Phase
Asthma	Drug: rosiglitazone	Phase II

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	The Effects of the PPARy Agonist Rosiglitazone on Airway Hyperreactivity

Resource links provided by NLM:

MedlinePlus related topics: Asthma

Drug Information available for: Rosiglitazone Rosiglitazone Maleate

U.S. FDA Resources

Further study details as provided by Creighton University:

Primary Outcome Measures:

Methacholine Responsiveness as Assessed by PC20, [ Time Frame: patients were assessed at baseline and at 12 weeks ] [ Designated as safety issue: No ]
PC20 is the concentration of methacholine at which patients had a decrease in Forced Expiratory Volume in one second (FEV1) of 20%

Secondary Outcome Measures:

Exhaled Nitric Oxide in Parts Per Billion (Ppb), Parts Per Billion [ Time Frame: patients were assessed at baseline and 12 weeks ] [ Designated as safety issue: No ]
Fraction Exhaled Nitric oxide was measured on each visit prior to bronchoprovocation by chemiluminescence using an analyzer.
Forced Expiratory Volume in 1 Second (FEV1) [ Time Frame: patients were assessed at baseline and 12 weeks ] [ Designated as safety issue: No ]
FEV1 in liters
Forced Expiratory Volume in One Second (FEV1) Percent Predicted [ Time Frame: patients were assessed at baseline and 12 weeks ] [ Designated as safety issue: No ]
Spirometry was performed on each visit according to American Thoracic Society guidelines. FEV1 percent predicted was measured.

Enrollment:	16
Study Start Date:	December 2008
Study Completion Date:	March 2010
Primary Completion Date:	February 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Subjects took rosiglitazone 2 mg for 4 weeks, then 4mg for 4 weeks, then 8 mg for 4 weeks	Drug: rosiglitazone 2mg, 4mg, 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.

Eligibility

Ages Eligible for Study:	19 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00614874

Locations

United States, Nebraska
Creighton University Medical Center, Department of Pulmonology and Critical Care
Omaha, Nebraska, United States, 68131

Sponsors and Collaborators

Creighton University

Investigators

Principal Investigator:

Tammy Wichman, MD

Creighton University Medical Center

More Information

Publications:

Matsuura H, Adachi H, Smart RC, Xu X, Arata J, Jetten AM. Correlation between expression of peroxisome proliferator-activated receptor beta and squamous differentiation in epidermal and tracheobronchial epithelial cells. Mol Cell Endocrinol. 1999 Jan 25;147(1-2):85-92.

Benayoun L, Letuve S, Druilhe A, Boczkowski J, Dombret MC, Mechighel P, Megret J, Leseche G, Aubier M, Pretolani M. Regulation of peroxisome proliferator-activated receptor gamma expression in human asthmatic airways: relationship with proliferation, apoptosis, and airway remodeling. Am J Respir Crit Care Med. 2001 Oct 15;164(8 Pt 1):1487-94.

Woerly G, Honda K, Loyens M, Papin JP, Auwerx J, Staels B, Capron M, Dombrowicz D. Peroxisome proliferator-activated receptors alpha and gamma down-regulate allergic inflammation and eosinophil activation. J Exp Med. 2003 Aug 4;198(3):411-21.

Lee KS, Kim SR, Park SJ, Park HS, Min KH, Jin SM, Lee MK, Kim UH, Lee YC. Peroxisome proliferator activated receptor-gamma modulates reactive oxygen species generation and activation of nuclear factor-kappaB and hypoxia-inducible factor 1alpha in allergic airway disease of mice. J Allergy Clin Immunol. 2006 Jul;118(1):120-7. Epub 2006 May 19.

Hammad H, de Heer HJ, Soullié T, Angeli V, Trottein F, Hoogsteden HC, Lambrecht BN. Activation of peroxisome proliferator-activated receptor-gamma in dendritic cells inhibits the development of eosinophilic airway inflammation in a mouse model of asthma. Am J Pathol. 2004 Jan;164(1):263-71.

Kim SR, Lee KS, Park HS, Park SJ, Min KH, Jin SM, Lee YC. Involvement of IL-10 in peroxisome proliferator-activated receptor gamma-mediated anti-inflammatory response in asthma. Mol Pharmacol. 2005 Dec;68(6):1568-75. Epub 2005 Sep 8.

Honda K, Marquillies P, Capron M, Dombrowicz D. Peroxisome proliferator-activated receptor gamma is expressed in airways and inhibits features of airway remodeling in a mouse asthma model. J Allergy Clin Immunol. 2004 May;113(5):882-8.

Ward JE, Gould H, Harris T, Bonacci JV, Stewart AG. PPAR gamma ligands, 15-deoxy-delta12,14-prostaglandin J2 and rosiglitazone regulate human cultured airway smooth muscle proliferation through different mechanisms. Br J Pharmacol. 2004 Feb;141(3):517-25. Epub 2004 Jan 12.

Wang AC, Dai X, Luu B, Conrad DJ. Peroxisome proliferator-activated receptor-gamma regulates airway epithelial cell activation. Am J Respir Cell Mol Biol. 2001 Jun;24(6):688-93.

Hashimoto Y, Nakahara K. Improvement of asthma after administration of pioglitazone. Diabetes Care. 2002 Feb;25(2):401. No abstract available.

Kharitonov SA, Gonio F, Kelly C, Meah S, Barnes PJ. Reproducibility of exhaled nitric oxide measurements in healthy and asthmatic adults and children. Eur Respir J. 2003 Mar;21(3):433-8.

Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med. 2006 Nov 23;355(21):2226-35. Review. No abstract available.

Responsible Party:	Tammy Wichman, Associate Professor of Medicine, Creighton University
ClinicalTrials.gov Identifier:	NCT00614874 History of Changes
Other Study ID Numbers:	07-14592
Study First Received:	January 31, 2008
Results First Received:	June 17, 2011
Last Updated:	September 1, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Creighton University:

Asthma
Avandia

Additional relevant MeSH terms:

Asthma
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate

Hypersensitivity
Immune System Diseases
Rosiglitazone
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on February 09, 2012