Study of Inhaled Carbon Monoxide to Treat Idiopathic Pulmonary Fibrosis

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

Detailed Description
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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.

Official Title
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Phase II Study of Inhaled CO for the Treatment of Idiopathic Pulmonary Fibrosis

Conditions
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Idiopathic Pulmonary Fibrosis

Intervention / Treatment
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* Drug: inhaled carbon monoxide
* Other: Oxygen


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: carbon monoxide inhalation<br>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. | Drug: inhaled carbon monoxide<br>* The intervention will be inhaled CO at 100-200 ppm administered two times weekly for two hours per dose to complete 12 weeks of treatment.<br>* Other names: CO;|
| Placebo Comparator: Oxygen 21%<br> | Other: Oxygen<br>* Room air oxygen concentrations will be administered as placebo<br>* Other names: O2;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum MMP7 Level | 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. | Baseline to Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total Lung Capacity % Predicted Values (TLC) | 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 | Baseline to Week 12 | 
| Diffusing Capacity for Carbon Monoxide (DLCO) % Predicted Values | 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 | Baseline to Week 12 | 
| Six Minute Walk Distance | 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 | Baseline to Week 12 | 
| St George's Respiratory Questionnaire | 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. | Baseline to Week 12 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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idiopathic pulmonary fibrosis, IPF, pulmonary fibrosis, carbon monoxide