The Use of Rosiglitazone to Treat Asthma

• Sponsor: Creighton University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00614874
• Collaborator: (none)
• Enrollment: 16
• Location: 1
• Arm: 1
• Duration (Months): 14.9
• Patients Per Site Per Month: 1.1

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: rosiglitazone	Phase 2

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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 16 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: The Effects of the PPARy Agonist Rosiglitazone on Airway Hyperreactivity
• Study Start Date: Dec 1, 2008
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
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

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. Forced Expiratory Volume in 1 Second (FEV1) [patients were assessed at baseline and 12 weeks]

   FEV1 in liters

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 19 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	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

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• Eder W, Ege MJ, von Mutius E. The asthma epidemic. N Engl J Med. 2006 Nov 23;355(21):2226-35. Review.
• 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.
• Hashimoto Y, Nakahara K. Improvement of asthma after administration of pioglitazone. Diabetes Care. 2002 Feb;25(2):401.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.

• Responsible Party: Tammy Wichman, Associate Professor of Medicine, Creighton University
• ClinicalTrials.gov Identifier: NCT00614874
• Other Study ID Numbers: 07-14592
• First Posted: Feb 13, 2008
• Last Update Posted: Sep 2, 2011
• Last Verified: Sep 1, 2011

• Keywords provided by Tammy Wichman, Associate Professor of Medicine, Creighton University: Asthma; Avandia
• Additional relevant MeSH terms: Asthma; Rosiglitazone

Study Results

Participant Flow

Recruitment Details	Recruitment was through pulmonary and allergy/immunology clinics from September 2008 to November 2009.
Pre-assignment Detail	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.

Arm/Group Title	Rosiglitazone
Arm/Group Description	Subjects will take rosiglitazone 2 mg for 4 weeks, then 4mg for 4 weeks, then 8 mg for 4 weeks
Period Title: Overall Study
STARTED	16
COMPLETED	14
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Rosiglitazone
Arm/Group Description	Subjects will take rosiglitazone 2 mg for 4 weeks, then 4mg for 4 weeks, then 8 mg for 4 weeks
Overall Participants	16
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	16 100%
>=65 years	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	34 (24)
Sex: Female, Male (Count of Participants)
Female	10 62.5%
Male	6 37.5%
Region of Enrollment (participants) [Number]
United States	16 100%

Outcome Measures

1. Primary Outcome

Title	Methacholine Responsiveness as Assessed by PC20,
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	Rosiglitazone
Arm/Group Description	Subjects will take rosiglitazone 2 mg for 4 weeks, then 4mg for 4 weeks, then 8 mg for 4 weeks
Measure Participants	13
Baseline	3.27 (2.34)
Week 12	8.71 (7.77)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rosiglitazone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.048
	Comments	Comparison is between baseline and week 12
	Method	ANOVA
	Comments

2. Secondary Outcome

Title	Exhaled Nitric Oxide in Parts Per Billion (Ppb), Parts Per Billion
Description	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

Outcome Measure Data

Analysis Population Description

2 patients withdrew from the study in visit 3

Arm/Group Title	Rosiglitazone
Arm/Group Description	Subjects will take rosiglitazone 2 mg for 4 weeks, then 4mg for 4 weeks, then 8 mg for 4 weeks
Measure Participants	14
Baseline	48 (32)
12 weeks	41 (35)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rosiglitazone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.183
	Comments	comparison was at baseline and week 12
	Method	Friedman
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	7
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 35
	Estimation Comments

3. Secondary Outcome

Title	Forced Expiratory Volume in 1 Second (FEV1)
Description	FEV1 in liters
Time Frame	patients were assessed at baseline and 12 weeks

Outcome Measure Data

Analysis Population Description

Two subjects withdrew from the study in visit 3

Arm/Group Title	Rosiglitazone
Arm/Group Description	Subjects will take rosiglitazone 2 mg for 4 weeks, then 4mg for 4 weeks, then 8 mg for 4 weeks
Measure Participants	14
Baseline	2.95 (0.89)
Week 12	3.04 (0.95)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Rosiglitazone
	Comments
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.398
	Comments	Comparison was at baseline and week 12
	Method	Friedman
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.09
	Confidence Interval	() 95%; to
	Parameter Dispersion	Type: Standard Deviation; Value: 0.95
	Estimation Comments

4. Secondary Outcome

Title	Forced Expiratory Volume in One Second (FEV1) Percent Predicted
Description	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

Outcome Measure Data

Analysis Population Description

Two subjects withdrew from the study in visit 3

Arm/Group Title	Rosiglitazone
Arm/Group Description	Subjects will take rosiglitazone 2 mg for 4 weeks, then 4mg for 4 weeks, then 8 mg for 4 weeks
Measure Participants	14
Baseline	82 (12)
Week 12	85 (15)

Adverse Events

Arm/Group Title	Rosiglitazone
Arm/Group Description	Subjects will take rosiglitazone 2 mg for 4 weeks, then 4mg for 4 weeks, then 8 mg for 4 weeks
All Cause Mortality
	Rosiglitazone
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Rosiglitazone
	Affected / at Risk (%)	# Events
Total	0/16 (0%)
Other (Not Including Serious) Adverse Events
	Rosiglitazone
	Affected / at Risk (%)	# Events
Total	0/16 (0%)

Limitations/Caveats

Small sample size. Lack of placebo control arm.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.