Carbon Monoxide Therapy for Severe Pulmonary Arterial Hypertension

NCT01523548 | Withdrawn Phase 1 DMC

• 2 other identifiers: 2010-06425K23HL098454
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Hypertension, Pulmonary

Keywords

Carbon Monoxide; Hypertension, Pulmonary

Outcome Measures

Primary Outcomes (1)

• Evidence of a 20% decrease in pulmonary vascular resistance post-therapy when compared to pre-therapy value

  At baseline and after 16 weeks

Secondary Outcomes (5)

• Effect of 16-weeks CO inhalation on other pulmonary and systemic hemodynamic parameters

  16 weeks

• Effect of 16-weeks CO inhalation on functional capacity assessed by six-minute walk test

  16 weeks

• Effect of 16-weeks CO inhalation on Brain Natriuretic Peptide levels

  16 weeks

• Effect of 16-weeks CO inhalation on right ventricular echocardiographic parameters

  16 weeks

• Effect of 16-weeks CO inhalation on acute pulmonary vasoreactivity

  16 weeks

Study Arms (1)

Carbon Monoxide

EXPERIMENTAL

Inhaled Carbon Monoxide therapy administered over 16 weeks

Drug: Carbon Monoxide

Interventions

Carbon Monoxide DRUG

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)

Carbon Monoxide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• male and female ≥ 18 years old , with Pulmonary Arterial Hypertension
• Right heart catheterization diagnosis of PAH:
• Mean Pulmonary Artery Pressure (mPAP)\> 25 mmHg at rest
• Pulmonary Capillary Occlusion Pressure (PCOP) or Left Ventricular End Diastolic Pressure (LVEDP) \< 15 mmHg
• Pulmonary Vascular Resistance (PVR) \> 3 mmHg/L/min
• Must be Class 1.1, 1.2, or 1.3 PAH (see Appendix A)
• Echocardiographic evidence of Right Ventricular Dysfunction
• On standard and stable PAH therapy (no dose changes in the 4 weeks prior to starting the study medication) including:
• A Prostacyclin (IV epoprostenol, IV or subcutaneous remodulin, inhaled iloprost or remodulin) unless willing or unable to tolerate therapy AND
• Phosphodiesterase type 5 inhibitor OR
• Endothelin Receptor Antagonist OR
• Any combination of a-c
• NYHA class III or IV despite 3 months of stable therapy as outlined above
• minute walk distance ≤ 380m
• Negative serum pregnancy test

You may not qualify if:

• History of malignancy in 2 years prior to enrollment
• Baseline cytopenia's:
• White blood cell count ≤ 3,000 i. Absolute Neutrophil Count (ANC) less than 1500 cells/mm3
• Hemoglobin ≤ 7
• Platelet ≤ 100,000
• Baseline Liver Disease:
• ALT/AST, ALk phos \> 2.5x ULN, INR \> 1.5
• Bilirubin \> 1.5 x ULN
• Coronary artery disease
• Any cause of pulmonary hypertension other than class 1.1, 1.2, or 1.3 PAH.
• Baseline Renal Disease: Cr ≥ 2
• Active Smoker
• Hypoxemia with SaO2 \< 95% on oxygen 2 L/min
• Baseline COHb \> 2%
• Pregnancy or lactation

Sponsors & Collaborators

• University of Illinois at Chicago: lead
• National Institutes of Health (NIH): collaborator
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

University of Illinois at Chicago Medical Center

Chicago, Illinois, 60612, United States

Location

MeSH Terms

Conditions

Hypertension, Pulmonary

Interventions

Carbon Monoxide

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Carbon Compounds, Inorganic; Inorganic Chemicals; Gases; Oxides; Oxygen Compounds

Study Officials

• Roberto F Machado, MD

  University of Illinois at Chicago

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pulmonary Medicine

Study Record Dates

• First Submitted: January 27, 2012
• First Posted: February 1, 2012
• Study Start: July 1, 2012
• Primary Completion: December 1, 2018
• Study Completion: December 1, 2018
• Last Updated: June 9, 2017

Record last verified: 2017-04

Locations

US (1)