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

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.

Study Overview

• Status: Completed
• Conditions: Chronic Obstructive Pulmonary Disease
• Intervention / Treatment: Drug: Placebo; Drug: Inhaled iloprost 5.0 mcg

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 Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Louisiana
    • New Orleans, Louisiana, United States, 70125
      • LSU Health Sciences Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo; Nebulized normal saline. Single administration	Drug: Placebo; Single administration; Other Names: Nebulized normal saline
Experimental: Inhaled iloprost 5.0 mcg; Single administration	Drug: Inhaled iloprost 5.0 mcg; Single administration; Other Names: Ventavis

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Louisiana State University Health Sciences Center in New Orleans
• Investigators: Principal Investigator: Matthew R Lammi, MD, LSU Health Sciences Center

Study record dates

Study Major Dates

• Study Start: September 1, 2013
• Primary Completion (Actual): November 1, 2016
• Study Completion (Actual): November 1, 2016

Study Registration Dates

• First Submitted: September 9, 2013
• First Submitted That Met QC Criteria: September 9, 2013
• First Posted (Estimate): September 13, 2013

Study Record Updates

• Last Update Posted (Estimate): December 16, 2016
• Last Update Submitted That Met QC Criteria: December 15, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Keywords: Oxidative stress; Chronic obstructive pulmonary disease; Inhaled iloprost; Cardiopulmonary exercise testing; Dynamic hyperinflation; B-type natriuretic peptide; Pulmonary vasculature; Inhaled prostacyclin
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Lung Diseases; Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Vasodilator Agents; Platelet Aggregation Inhibitors; Iloprost
• Other Study ID Numbers: GM104940-50346-S