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

Phase 2

Completed

• Conditions: Chronic Obstructive Pulmonary Disease
• Interventions: Drug: Placebo; Drug: Inhaled iloprost 5.0 mcg

• Registration Number: NCT01941225
• Lead Sponsor: Louisiana State University Health Sciences Center in New Orleans

Brief Summary

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

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

Study Timeline

• Study Start: 2013-09
• Study First Submitted: 2013-09-09
• Study First Submitted QC: 2013-09-09
• Study First Posted: 2013-09-13
• Primary Completion: 2016-11
• Study Completion: 2016-11
• Status Verified: 2016-12
• Last Update Submitted: 2016-12-15
• Last Update Posted: 2016-12-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 24

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Nebulized normal saline. Single administration
Inhaled iloprost 5.0 mcg	Inhaled iloprost 5.0 mcg	Single administration

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

LSU Health Sciences Center; 🇺🇸 New Orleans, Louisiana, United States