The Use of Rosiglitazone to Treat Asthma

Condition(s) targeted: Asthma

Intervention: rosiglitazone (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Creighton University

Official(s) and/or principal investigator(s):
Tammy Wichman, MD, Principal Investigator, Affiliation: Creighton University Medical Center

Overall contact:
Lori Mahon, RN, Phone: 402-280-5968, Email: lmahon@creighton.edu

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.

Official title: The Effects of the PPARy Agonist Rosiglitazone on Airway Hyperreactivity

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

Primary outcome: To examine whether rosiglitazone changes airway hyperreactivity in steroid naive asthmatics by measuring methacholine responsiveness

Secondary outcome:

To examine whether rosiglitazone changes inflammation in asthmatics by measuring the level of exhaled nitric oxide

To examine whether or not it changes pulmonary function in asthmatics by measuring spirometry and impulse oscillometry.

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 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.

Minimum age: 19 Years. Maximum age: N/A. Gender(s): Both.

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

Lori Mahon, RN, Phone: 402-280-5968, Email: lmahon@creighton.edu

Creighton University Medical Center, Department of Pulmonology and Critical Care, Omaha, Nebraska 68131, United States; Recruiting
Tammy Wichman, MD, Principal Investigator

Related 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.

Starting date: December 2007
Ending date: December 2010
Last updated: September 1, 2009