The Use of Rosiglitazone to Treat Asthma

NCT00614874 | Completed Phase 2 Results

• 1 other identifier: 07-14592
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Keywords

Asthma; Avandia

Outcome Measures

Primary Outcomes (1)

• 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%

  patients were assessed at baseline and at 12 weeks

Secondary Outcomes (3)

• Exhaled Nitric Oxide in Parts Per Billion (Ppb), Parts Per Billion

  patients were assessed at baseline and 12 weeks

• Forced Expiratory Volume in 1 Second (FEV1)

  patients were assessed at baseline and 12 weeks

• Forced Expiratory Volume in One Second (FEV1) Percent Predicted

  patients were assessed at baseline and 12 weeks

Study Arms (1)

1

EXPERIMENTAL

Subjects took rosiglitazone 2 mg for 4 weeks, then 4mg for 4 weeks, then 8 mg for 4 weeks

Drug: rosiglitazone

Interventions

rosiglitazone DRUG

2mg, 4mg, 8mg

1

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Creighton University: lead

Study Sites (1)

Creighton University Medical Center, Department of Pulmonology and Critical Care

Omaha, Nebraska, 68131, United States

Location

Related Publications (12)

• 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. doi: 10.1016/s0303-7207(98)00214-7.

  PMID: 10195695 BACKGROUND

• 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. doi: 10.1164/ajrccm.164.8.2101070.

  PMID: 11704601 BACKGROUND

• 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. doi: 10.1084/jem.20021384.

  PMID: 12900517 BACKGROUND

• 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. doi: 10.1016/j.jaci.2006.03.021. Epub 2006 May 19.

  PMID: 16815147 BACKGROUND

• Hammad H, de Heer HJ, Soullie 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. doi: 10.1016/s0002-9440(10)63116-1.

  PMID: 14695339 BACKGROUND

• 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. doi: 10.1124/mol.105.017160. Epub 2005 Sep 8.

  PMID: 16150927 BACKGROUND

• 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. doi: 10.1016/j.jaci.2004.02.036.

  PMID: 15131570 BACKGROUND

• 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. doi: 10.1038/sj.bjp.0705630. Epub 2004 Jan 12.

  PMID: 14718259 BACKGROUND

• 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. doi: 10.1165/ajrcmb.24.6.4376.

  PMID: 11415933 BACKGROUND

• Hashimoto Y, Nakahara K. Improvement of asthma after administration of pioglitazone. Diabetes Care. 2002 Feb;25(2):401. doi: 10.2337/diacare.25.2.401. No abstract available.

  PMID: 11815521 BACKGROUND

• 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. doi: 10.1183/09031936.03.00066903a.

  PMID: 12661997 BACKGROUND

• Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med. 2006 Nov 23;355(21):2226-35. doi: 10.1056/NEJMra054308. No abstract available.

  PMID: 17124020 BACKGROUND

MeSH Terms

Conditions

Asthma

Interventions

Rosiglitazone

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Limitations and Caveats

Small sample size. Lack of placebo control arm.

Results Point of Contact

• Title: Dr. Tammy Wichman
• Organization: Creighton University School of Medicine

wichman@creighton.edu

402-449-4486

Study Officials

• Tammy Wichman, MD

  Creighton University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: January 31, 2008
• First Posted: February 13, 2008
• Study Start: December 1, 2008
• Primary Completion: February 1, 2010
• Study Completion: March 1, 2010
• Last Updated: September 2, 2011
• Results First Posted: September 2, 2011

Record last verified: 2011-09

Locations

US (1)