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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| 1 | Experimental | Subjects took rosiglitazone 2 mg for 4 weeks, then 4mg for 4 weeks, then 8 mg for 4 weeks |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| rosiglitazone | Drug | 2mg, 4mg, 8mg |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Exhaled Nitric Oxide in Parts Per Billion (Ppb), Parts Per Billion | Fraction Exhaled Nitric oxide was measured on each visit prior to bronchoprovocation by chemiluminescence using an analyzer. | patients were assessed at baseline and 12 weeks |
| Forced Expiratory Volume in 1 Second (FEV1) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Tammy Wichman, MD | Creighton University Medical Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Creighton University Medical Center, Department of Pulmonology and Critical Care | Omaha | Nebraska | 68131 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 10195695 | Background | 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. | |
| 11704601 | Background |
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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.
Recruitment was through pulmonary and allergy/immunology clinics from September 2008 to November 2009.
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| ID | Title | Description |
|---|---|---|
| FG000 | Rosiglitazone | Subjects will take rosiglitazone 2 mg for 4 weeks, then 4mg for 4 weeks, then 8 mg for 4 weeks |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Rosiglitazone | Subjects will take rosiglitazone 2 mg for 4 weeks, then 4mg for 4 weeks, then 8 mg for 4 weeks |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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% | 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. | Posted | Mean | Standard Deviation | mg/mL | patients were assessed at baseline and at 12 weeks |
|
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Rosiglitazone | Subjects will take rosiglitazone 2 mg for 4 weeks, then 4mg for 4 weeks, then 8 mg for 4 weeks |
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Small sample size. Lack of placebo control arm.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Tammy Wichman | Creighton University School of Medicine | 402-449-4486 | wichman@creighton.edu |
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| ID | Term |
|---|---|
| D001249 | Asthma |
| ID | Term |
|---|---|
| D001982 | Bronchial Diseases |
| D012140 | Respiratory Tract Diseases |
| D008173 | Lung Diseases, Obstructive |
| D008171 | Lung Diseases |
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| ID | Term |
|---|---|
| D000077154 | Rosiglitazone |
| ID | Term |
|---|---|
| D045162 | Thiazolidinediones |
| D013844 | Thiazoles |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
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FEV1 in liters |
| patients were assessed at baseline and 12 weeks |
| Forced Expiratory Volume in One Second (FEV1) Percent Predicted | Spirometry was performed on each visit according to American Thoracic Society guidelines. FEV1 percent predicted was measured. | patients were assessed at baseline and 12 weeks |
| 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. |
| 12900517 | 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. |
| 16815147 | 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. |
| 14695339 | 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. |
| 16150927 | 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. |
| 15131570 | 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. |
| 14718259 | 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. |
| 11415933 | 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. |
| 11815521 | 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. |
| 12661997 | 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. |
| 17124020 | 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. |
| Participants |
|
| Age Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Participants |
|
|
|
| Secondary | Exhaled Nitric Oxide in Parts Per Billion (Ppb), Parts Per Billion | Fraction Exhaled Nitric oxide was measured on each visit prior to bronchoprovocation by chemiluminescence using an analyzer. | 2 patients withdrew from the study in visit 3 | Posted | Mean | Standard Deviation | parts per billion | patients were assessed at baseline and 12 weeks |
|
|
|
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| Secondary | Forced Expiratory Volume in 1 Second (FEV1) | FEV1 in liters | Two subjects withdrew from the study in visit 3 | Posted | Mean | Standard Deviation | Liters | patients were assessed at baseline and 12 weeks |
|
|
|
|
| Secondary | Forced Expiratory Volume in One Second (FEV1) Percent Predicted | Spirometry was performed on each visit according to American Thoracic Society guidelines. FEV1 percent predicted was measured. | Two subjects withdrew from the study in visit 3 | Posted | Mean | Standard Deviation | percent predicted | patients were assessed at baseline and 12 weeks |
|
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| 0 |
| 16 |
| 0 |
| 16 |
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| D012130 |
| Respiratory Hypersensitivity |
| D006969 | Hypersensitivity, Immediate |
| D006967 | Hypersensitivity |
| D007154 | Immune System Diseases |
| D001393 |
| Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |