Inhaled Iloprost, Dynamic Hyperinflation, and Oxidative Stress in COPD Patients

Study Overview
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Brief Summary
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The purpose of this study is to investigate the role of the pulmonary vasculature in the development and progression of chronic obstructive pulmonary disease (COPD). To accomplish this, an inhaled prostacyclin (iloprost) will be given to patients with COPD and changes in oxidative stress and lung volumes during exercise will be measured.

Detailed Description
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Chronic obstructive pulmonary disease (COPD), the 3rd leading cause of death in the US, is a progressive disorder for which new treatments are urgently needed, as existing therapies are focused primarily on symptom relief. Oxidative stress, in part arising from inducible nitric oxide synthase (iNOS) released by the pulmonary vasculature, is critical for the development and progression of COPD; a treatment strategy focused on the pulmonary vasculature is hypothesized to be beneficial in COPD patients. This will be studied with the use of an inhaled prostacyclin analogue, iloprost, which has been approved for pulmonary hypertension and investigated in small studies of COPD patients. Potential mechanisms include reductions in dynamic hyperinflation during exercise in COPD patients or improvements in oxidative stress

Official Title
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Inhaled Iloprost, Dynamic Hyperinflation, and Oxidative Stress in COPD Patients

Conditions
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Chronic Obstructive Pulmonary Disease

Intervention / Treatment
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* Drug: Inhaled iloprost 5.0 mcg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 40 years old or older Physician diagnosis of chronic obstructive pulmonary disease 10 or more pack-year smoking history FEV1/FVC <0.70 FEV1 35-80% of predicted Exclusion Criteria: Acute exacerbation of COPD within the last 30 days Pregnant or breast-feeding Contraindications to cardiopulmonary exercise testing Known intolerance or allergy to iloprost On oral corticosteroids (may be included if off for 7 days prior to testing) Supplemental oxygen need Known inflammatory disease other than COPD Active solid organ/hematologic malignancy

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Nebulized normal saline. Single administration | Drug: Placebo<br>* Single administration<br>* Other names: Nebulized normal saline;|
| Experimental: Inhaled iloprost 5.0 mcg<br>Single administration | Drug: Inhaled iloprost 5.0 mcg<br>* Single administration<br>* Other names: Ventavis;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dynamic hyperinflation during maximal cardiopulmonary exercise test | Dynamic hyperinflation will be measured as EELV/TLC ratio (end-expiratory lung volume/total lung capacity ratio) during exercise | Acute response (exercise testing performed 30 minutes after study drug administration) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood markers of oxidative stress | 8-isoprostane, superoxide dismutase, catalase, nitrite, malondialdehyde | Acute response (measured 10 minutes, 30 minutes, 40 minutes, and 100 minutes after study drug administration) | 
| Blood markers of inflammation | IL-1 beta, IL-6, IL-8, IL-10, IL-13, IL-18, TNF-alpha | Acute response (measured 10 minutes, 30 minutes, 40 minutes, and 100 minutes after study drug administration) | 
| Dead space fraction |  | Acute response (measured every 2 minutes during exercise, starting 30 minutes after study drug administration) | 
| B-type natriuretic peptide |  | Acute response (measured 30 and 40 minutes after study drug administration) | 
| Partial pressure of oxygen |  | Acute response (measured 30 minutes after study drug administration and every 2 minutes during exercise) | 
| Metabolic and gas exchange parameters during cardiopulmonary exercise test |  | Acute response (throughout exercise, starting 30 minutes after study drug administration) | 
| Blood cyclic AMP levels |  | Acute response (measured 10 minutes, 30 minutes, 40 minutes, and 100 minutes after study drug administration) | 
| Blood iloprost levels |  | Acute response (measured 10 minutes, 30 minutes, 40 minutes, and 100 minutes after study drug administration) | 
| Exercise time and external work performed |  | measured during exercise test 30 minutes after study drug administration | 
| Borg dyspnea and leg scores |  | During exericse (starting 30 minutes after study drug administration) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic obstructive pulmonary disease, Pulmonary vasculature, Inhaled iloprost, Inhaled prostacyclin, Dynamic hyperinflation, Oxidative stress, Cardiopulmonary exercise testing, B-type natriuretic peptide