Carbon Monoxide Therapy for Severe Pulmonary Arterial Hypertension (CO in PAH)
The purpose of this study is to examine the potential of carbon monoxide (CO) to decrease elevated blood pressure in the pulmonary artery. This symptom is seen in patients with pulmonary arterial hypertension, a rare disease that causes fatigue, dizziness, and shortness of breath because the blood vessels that supply the lungs narrow, forcing the heart to work harder to push blood through. Previous studies in the laboratory have shown that carbon monoxide has promise in treating these symptoms.
Subjects in this study are being asked to undergo a new type of treatment to improve pulmonary arterial hypertension by breathing CO gas. CO is a colorless, tasteless, odorless gas usually found in car exhaust or cigarette smoke. It is administered with a continuous flow of air. Subjects will undergo a screening process during which it will be determined if they are eligible for the study. After the screening process, if subjects meet eligibility criteria for the study, they will begin carbon monoxide treatment through a cushioned mask that is placed over the nose and mouth. This treatment will last for sixteen weeks.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Carbon Monoxide Therapy for Severe Pulmonary Arterial Hypertension|
- Evidence of a 20% decrease in pulmonary vascular resistance post-therapy when compared to pre-therapy value [ Time Frame: At baseline and after 16 weeks ] [ Designated as safety issue: No ]
- Effect of 16-weeks CO inhalation on other pulmonary and systemic hemodynamic parameters [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
- Effect of 16-weeks CO inhalation on functional capacity assessed by six-minute walk test [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
- Effect of 16-weeks CO inhalation on Brain Natriuretic Peptide levels [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
- Effect of 16-weeks CO inhalation on right ventricular echocardiographic parameters [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
- Effect of 16-weeks CO inhalation on acute pulmonary vasoreactivity [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||July 2012|
|Estimated Study Completion Date:||December 2015|
|Estimated Primary Completion Date:||December 2015 (Final data collection date for primary outcome measure)|
Experimental: Carbon Monoxide
Inhaled Carbon Monoxide therapy administered over 16 weeks
Drug: Carbon Monoxide
150 ppm x 3 hours once weekly (week 1) 150 ppm x 3 hours twice weekly (week 2) 150 ppm x 3 hours three times a week (week 3-16)
Pulmonary arterial hypertension (PAH) remains an uncommon debilitating and fatal disease, and is clinically marked by a progressive increase in pulmonary vascular resistance leading to right heart failure and ultimately death. Currently the treatment options available for those suffering from PAH target cellular dysfunction that leads to constriction of the vasculature. Although there is some evidence that available therapies have secondary effects on vascular remodeling there are currently no therapies that target abnormal cell proliferation in PAH.
Carbon monoxide (CO) is a gaseous molecule with known toxicity and lethality to living organisms when exposed to high concentrations for sustained periods. However, CO has shown promise in preclinical models of pulmonary hypertension. Recent studies have shown that mammalian cells have the ability to generate endogenous CO primarily through the catalysis of heme by the heme oxygenase enzymatic system and there is ample evidence demonstrating that CO behaves as a signaling molecule in cellular and biological processes. Furthermore, CO has been demonstrated to exert key physiological and protective functions in various models of tissue inflammation and injury.
This study will evaluate the safety and potential efficacy of inhaled CO in subjects with severe PAH. Over forty subjects with severe PAH despite best available therapy will be screened from the UIC pulmonary vascular disease clinic, of which twenty subjects will be recruited for participation in the trial. The trial will consist of an initial screening period to determine subjects' eligibility for the study. This will be based on a previous echocardiogram, a six minute walk test and right heart catheterization done as part of standard care for subjects with pulmonary arterial hypertension. Following the initial screening, the trial will last sixteen weeks, during which subjects will receive inhaled carbon monoxide up to three times weekly at the University of Illinois at Chicago.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01523548
|United States, Illinois|
|University of Illinois at Chicago Medical Center|
|Chicago, Illinois, United States, 60612|
|Principal Investigator:||Roberto F Machado, MD||University of Illinois at Chicago|