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| ID | Type | Description | Link |
|---|---|---|---|
| 1U01HL105371 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Heart, Lung, and Blood Institute (NHLBI) | NIH |
| University of California, San Francisco | OTHER |
| University of Chicago | OTHER |
| University of Illinois at Chicago |
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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| carbon monoxide inhalation | Experimental | 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. |
|
| Oxygen 21% | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| inhaled carbon monoxide | Drug | 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. |
|
| 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 |
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Rosas O Ivan, MD | Brigham and Women's Hospital | Principal Investigator |
| Joe GN Garcia, MD | University of Illinois at Chicago | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of California San Francisco | San Francisco | California | 94143 | United States | ||
| University of Illinois Chicago |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 29100885 | Derived | 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. |
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Sixty-five subjects were screened, of which 7 subjects were screen failures. Reasons for screen failure included subjects who completed screening changed their mind about participation before visit 2, FEV1/FVC less than 70% predicted, and infection within 1 month before screening. The screening period up to 28 days from date of consent to Visit 2.
The enrollment period opened on 11/29/2011 and was closed on 1/10/2014 when the study reached its enrollment target of 58 subjects. Subjects were enrolled at 8 participating academic medical centers.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. 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. |
| FG001 | Oxygen 21% | Oxygen: Room air oxygen concentrations will be administered as placebo |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. 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. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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. | One subject randomized to placebo withdrew consent prior to the MMP7 blood draw at visit 2. This is missing data and the reason why we have n=28 for placebo group. | Posted | Least Squares Mean | Standard Error | ng/ml | Baseline to Week 12 |
|
Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. 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. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Ivan Rosas, MD | Brigham and Women's Hospital | 617-278-0434 | irosas@rics.bwh.harvard.edu |
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| ID | Term |
|---|---|
| D054990 | Idiopathic Pulmonary Fibrosis |
| D011658 | Pulmonary Fibrosis |
| ID | Term |
|---|---|
| D017563 | Lung Diseases, Interstitial |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D005355 | Fibrosis |
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| ID | Term |
|---|---|
| D010100 | Oxygen |
| ID | Term |
|---|---|
| D018011 | Chalcogens |
| D004602 | Elements |
| D007287 | Inorganic Chemicals |
| D005740 | Gases |
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| OTHER |
| University of Michigan | OTHER |
| Columbia University | OTHER |
| Tulane University | OTHER |
| University of Washington | OTHER |
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|
| Oxygen | Other | Room air oxygen concentrations will be administered as placebo |
|
|
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 |
| Chicago |
| Illinois |
| 60612 |
| United States |
| University of Chicago | Chicago | Illinois | 60637 | United States |
| Tulane University | New Orleans | Louisiana | 70112 | United States |
| Brigham and Women's Hospital | Boston | Massachusetts | 02115 | United States |
| University of Michigan | Ann Arbor | Michigan | 48109 | United States |
| Columbia University | New York | New York | 10032 | United States |
| University of Washington | Seattle | Washington | 98195 | United States |
| Withdrawal by Subject |
|
| BG001 |
| Oxygen 21% |
Oxygen: Room air oxygen concentrations will be administered as placebo |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 | Oxygen 21% | Oxygen: Room air oxygen concentrations will be administered as placebo |
|
|
|
| Secondary | 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 | Posted | Least Squares Mean | Standard Error | % Predicted | Baseline to Week 12 |
|
|
|
|
| Secondary | 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 | Posted | Least Squares Mean | Standard Error | % predicted | Baseline to Week 12 |
|
|
|
|
| Secondary | 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 | Posted | Least Squares Mean | Standard Error | meters | Baseline to Week 12 |
|
|
|
|
| Secondary | 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. | Posted | Least Squares Mean | Standard Error | Total Score | Baseline to Week 12 |
|
|
|
|
| 3 |
| 29 |
| 28 |
| 29 |
| EG001 | Oxygen 21% | Oxygen: Room air oxygen concentrations will be administered as placebo | 7 | 29 | 19 | 29 |
| IPF progression | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Acute pancreatitis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Acute Coronary Syndrome | Cardiac disorders | CTCAE (4.0) | Systematic Assessment |
|
| Worsening Cirrhosis | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Colonic Obstruction | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Acute syndrome of innapropriate antidiuretic hormone (SIADH) | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4.0) | Systematic Assessment |
|
| Pneumothorax | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Small Cell Cancer | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | CTCAE (4.0) | Systematic Assessment |
|
| Worsening of Shortness of Breath | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Pulmonary Fibrosis Related Death | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Diarrhea | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
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| Dizziness | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Dyspnea | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Gastroesophageal reflux disease | Gastrointestinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Fatigue | General disorders | CTCAE (4.0) | Systematic Assessment |
|
| Headache | Nervous system disorders | CTCAE (4.0) | Systematic Assessment |
|
| Nasal Congestion | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment | Common Cold symptom |
|
| Productive Cough | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | CTCAE (4.0) | Systematic Assessment |
|
| Wheezing | Respiratory, thoracic and mediastinal disorders | CTCAE (4.0) | Systematic Assessment |
|
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| D010335 |
| Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |