Study of Inhaled Carbon Monoxide to Treat Idiopathic Pulmonary Fibrosis

Phase 2

Completed

• Conditions: Idiopathic Pulmonary Fibrosis
• Interventions: Other: Oxygen; Drug: inhaled carbon monoxide

• Registration Number: NCT01214187
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

The purpose of this study is to determine whether low concentration inhaled carbon monoxide is effective in treating idiopathic pulmonary fibrosis.

Detailed Description

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by destruction of normal epithelial structure, proliferation of fibroblasts, and deposition of connective-tissue matrix proteins. There are currently no effective therapies for IPF. Over the past two decades, preclinical studies of inhaled low dose carbon monoxide (CO) have shown that this biologically active diatomic gas possesses properties that would make it a viable novel therapy for IPF. CO therapy has been well tolerated in Phase I and Phase II human trials to date. This phase II study is designed to investigate whether IPF patients show evidence of decreased peripheral blood levels of matrix metalloproteinase-7 (MMP7) and stability of secondary indicators of disease progression after 3 months of inhaled therapy.

Study Timeline

• Study First Submitted: 2010-09-30
• Study First Submitted QC: 2010-10-01
• Study First Posted: 2010-10-04
• Study Start: 2011-07
• Primary Completion: 2014-10
• Study Completion: 2015-04
• Results First Submitted: 2017-03-01
• Status Verified: 2017-05
• Results First Submitted QC: 2017-05-18
• Last Update Submitted: 2017-05-18
• Results First Posted: 2017-06-14
• Last Update Posted: 2017-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 58

Inclusion Criteria

• Adults above the age of 18 and equal to or below the age of 85
• Diagnosis of IPF by biopsy or
• American Thoracic Society (ATS)/European Respiratory Society (ERS)/ Latin American Thoracic Association (ALAT) Guidelines (Am J Respir Crit Care Med Vol 183. pp 788-824,2011)
• Forced vital capacity (FVC) greater than or equal to 50% predicted, greater than or equal to one month off all medications prescribed for IPF

Exclusion Criteria

• Evidence of active infection within the last month
• Significant obstructive respiratory defect
• Supplemental oxygen required to maintain an oxygen saturation over 88% at rest
• History of myocardial infarction within the last year, heart failure within the last 3 years or cardiac arrhythmia requiring drug therapy
• History of smoking within 4 weeks of screening
• Pregnancy or lactation
• Participation in another therapeutic clinical trial

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Oxygen 21%	Oxygen	-
carbon monoxide inhalation	inhaled carbon monoxide	The primary intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.

Primary Outcome Measures

Name	Time	Method
Serum MMP7 Level	Baseline to Week 12	The primary study endpoint was the change in MMP7 serum concentration (ng/ml) from baseline to 12 weeks. Serum MMP7 concentrations in peripheral blood are easily measureable and reflect changes in the alveolar microenvironment. Thus, we have chosen to study mean serum MMP7 concentrations after three months of CO treatment as a surrogate biomarker of the effect of inhaled CO administration on disease progression.

Secondary Outcome Measures

Name	Time	Method
Total Lung Capacity % Predicted Values (TLC)	Baseline to Week 12	Total lung capacity % predicted values (TLC) is a major clinical determinant of restrictive lung disease in practice, with TLC measurement below the 5th percentile of the predicted value indicative of a restrictive ventilatory defect
St George's Respiratory Questionnaire	Baseline to Week 12	St. George's Respiratory Questionnaire (SGRQ) is a validated self-reported instrument. In this instrument, scores range from 0 to 100, with higher scores reflective of worse quality of life.
Six Minute Walk Distance	Baseline to Week 12	The six minute walk distance is commonly used both in research studies and in clinical practice as a measure of functional capabilities, and changes in six minute walk distance and oxygen use during testing over time often reflect clinically relevant disease progression. We will measure the distance travelled during six minutes (meters) in accordance with published guidelines
Diffusing Capacity for Carbon Monoxide (DLCO) % Predicted Values	Baseline to Week 12	Interstitial changes associated with IPF can worsen diffusing capabilities across the alveolar-capillary membrane. As a result, diffusing capacity of carbon monoxide is an important outcome to assess architectural distortion and resultant decrements in diffusing capabilities

Trial Locations

Locations (8)

Columbia University; 🇺🇸 New York, New York, United States

University of Chicago; 🇺🇸 Chicago, Illinois, United States

University of Illinois Chicago; 🇺🇸 Chicago, Illinois, United States

University of California San Francisco; 🇺🇸 San Francisco, California, United States

Tulane University; 🇺🇸 New Orleans, Louisiana, United States

University of Washington; 🇺🇸 Seattle, Washington, United States

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States

University of Michigan; 🇺🇸 Ann Arbor, Michigan, United States