Study of Inhaled Carbon Monoxide to Treat Idiopathic Pulmonary Fibrosis

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

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

Study Overview

• Status: Completed
• Conditions: Idiopathic Pulmonary Fibrosis
• Intervention / Treatment: Drug: inhaled carbon monoxide; Other: Oxygen

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 Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California San Francisco
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago
    • Chicago, Illinois, United States, 60612
      • University of Illinois Chicago
  • Louisiana
    • New Orleans, Louisiana, United States, 70112
      • Tulane University
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Brigham and Women's Hospital
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • University of Michigan
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • Washington
    • Seattle, Washington, United States, 98195
      • University of Washington

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: CO
PLACEBO_COMPARATOR: Oxygen 21%	Other: Oxygen; Room air oxygen concentrations will be administered as placebo; Other Names: O2

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); University of Chicago; Columbia University; University of Michigan; University of Illinois at Chicago; University of Washington; Tulane University; University of California, San Francisco
• Investigators: Principal Investigator: Rosas O Ivan, MD, Brigham and Women's Hospital; Principal Investigator: Joe GN Garcia, MD, University of Illinois at Chicago

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: July 1, 2011
• Primary Completion (ACTUAL): October 1, 2014
• Study Completion (ACTUAL): April 1, 2015

Study Registration Dates

• First Submitted: September 30, 2010
• First Submitted That Met QC Criteria: October 1, 2010
• First Posted (ESTIMATE): October 4, 2010

Study Record Updates

• Last Update Posted (ACTUAL): June 14, 2017
• Last Update Submitted That Met QC Criteria: May 18, 2017
• Last Verified: May 1, 2017

More Information

Terms related to this study

• Keywords: idiopathic pulmonary fibrosis; IPF; pulmonary fibrosis; carbon monoxide
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Lung Diseases; Fibrosis; Pulmonary Fibrosis; Idiopathic Pulmonary Fibrosis; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Antimetabolites; Gasotransmitters; Carbon Monoxide
• Other Study ID Numbers: 1U01HL105371 (NIH)