Study of Inhaled Carbon Monoxide to Treat Idiopathic Pulmonary Fibrosis

• ClinicalTrials.gov Identifier: NCT01214187
• Recruitment Status: Completed
• First Posted: October 4, 2010
• Results First Posted: June 14, 2017
• Last Update Posted: June 14, 2017
• Sponsor: Brigham and Women's Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); University of California, San Francisco; University of Chicago; University of Illinois at Chicago; University of Michigan; Columbia University; Tulane University; University of Washington
• Information provided by (Responsible Party): Ivan O. Rosas, Brigham and Women's Hospital

Study Description

Brief Summary:

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

Condition or disease	Intervention/treatment	Phase
Idiopathic Pulmonary Fibrosis	Drug: inhaled carbon monoxide; Other: Oxygen	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 58 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Care Provider)
• Primary Purpose: Treatment
• Official Title: Phase II Study of Inhaled CO for the Treatment of Idiopathic Pulmonary Fibrosis
• Study Start Date: July 2011
• Actual Primary Completion Date: October 2014
• Actual Study Completion Date: April 2015

Arms and Interventions

Arm	Intervention/treatment
Experimental: carbon monoxide inhalation; 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; 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.; Other Name: CO
Placebo Comparator: Oxygen 21%	Other: Oxygen; Room air oxygen concentrations will be administered as placebo; Other Name: O2

Outcome Measures

Primary Outcome Measures :

1. Serum MMP7 Level [ Time Frame: 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 :

1. Total Lung Capacity % Predicted Values (TLC) [ Time Frame: 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
2. Diffusing Capacity for Carbon Monoxide (DLCO) % Predicted Values [ Time Frame: 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
3. Six Minute Walk Distance [ Time Frame: 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
4. St George's Respiratory Questionnaire [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 85 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Locations

United States, California

University of California San Francisco

San Francisco, California, United States, 94143

United States, Illinois

University of Illinois Chicago

Chicago, Illinois, United States, 60612

University of Chicago

Chicago, Illinois, United States, 60637

United States, Louisiana

Tulane University

New Orleans, Louisiana, United States, 70112

United States, Massachusetts

Brigham and Women's Hospital

Boston, Massachusetts, United States, 02115

United States, Michigan

University of Michigan

Ann Arbor, Michigan, United States, 48109

United States, New York

Columbia University

New York, New York, United States, 10032

United States, Washington

University of Washington

Seattle, Washington, United States, 98195

Sponsors and Collaborators

Brigham and Women's Hospital

National Heart, Lung, and Blood Institute (NHLBI)

University of California, San Francisco

University of Chicago

University of Illinois at Chicago

University of Michigan

Columbia University

Tulane University

University of Washington

Investigators

• Principal Investigator: Rosas O Ivan, MD; Brigham and Women's Hospital
• Principal Investigator: Joe GN Garcia, MD; University of Illinois at Chicago

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Rosas IO, Goldberg HJ, Collard HR, El-Chemaly S, Flaherty K, Hunninghake GM, Lasky JA, Lederer DJ, Machado R, Martinez FJ, Maurer R, Teller D, Noth I, Peters E, Raghu G, Garcia JGN, Choi AMK. A Phase II Clinical Trial of Low-Dose Inhaled Carbon Monoxide in Idiopathic Pulmonary Fibrosis. Chest. 2018 Jan;153(1):94-104. doi: 10.1016/j.chest.2017.09.052. Epub 2017 Oct 31.

• Responsible Party: Ivan O. Rosas, Overall Principle Investigator, Brigham and Women's Hospital
• ClinicalTrials.gov Identifier: NCT01214187
• Other Study ID Numbers: 1U01HL105371 ( U.S. NIH Grant/Contract ); 1U01HL105371 ( U.S. NIH Grant/Contract )
• First Posted: October 4, 2010
• Results First Posted: June 14, 2017
• Last Update Posted: June 14, 2017
• Last Verified: May 2017

Keywords provided by Ivan O. Rosas, Brigham and Women's Hospital:

idiopathic pulmonary fibrosis; IPF; pulmonary fibrosis; carbon monoxide

Additional relevant MeSH terms:

Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Fibrosis; Pathologic Processes; Lung Diseases; Respiratory Tract Diseases; Carbon Monoxide; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Gasotransmitters; Neurotransmitter Agents; Physiological Effects of Drugs