ClinicalTrials.gov
ClinicalTrials.gov Menu

Study of Inhaled Carbon Monoxide to Treat Idiopathic Pulmonary Fibrosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
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:
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 Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Double (Participant, Care Provider);   Primary Purpose: Treatment
Condition Idiopathic Pulmonary Fibrosis
Interventions Drug: inhaled carbon monoxide
Other: Oxygen
Enrollment 58
Recruitment Details 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.
Pre-assignment Details 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.
Arm/Group Title Carbon Monoxide Inhalation Oxygen 21%
Hide Arm/Group Description

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.

Oxygen: Room air oxygen concentrations will be administered as placebo
Period Title: Overall Study
Started 29 29
Completed 22 23
Not Completed 7 6
Reason Not Completed
Adverse Event             6             2
Death             1             1
Withdrawal by Subject             0             3
Arm/Group Title Carbon Monoxide Inhalation Oxygen 21% Total
Hide Arm/Group Description

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.

Oxygen: Room air oxygen concentrations will be administered as placebo Total of all reporting groups
Overall Number of Baseline Participants 29 29 58
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 29 participants 29 participants 58 participants
66.6  (6.1) 68.6  (8.4) 68  (7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 29 participants 58 participants
Female
4
  13.8%
7
  24.1%
11
  19.0%
Male
25
  86.2%
22
  75.9%
47
  81.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 29 participants 29 participants 58 participants
Hispanic or Latino
1
   3.4%
2
   6.9%
3
   5.2%
Not Hispanic or Latino
28
  96.6%
27
  93.1%
55
  94.8%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 29 participants 29 participants 58 participants
29 29 58
1.Primary Outcome
Title Serum MMP7 Level
Hide Description 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.
Time Frame Baseline to Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
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.
Arm/Group Title Carbon Monoxide Inhalation Oxygen 21%
Hide Arm/Group Description:

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.

Oxygen: Room air oxygen concentrations will be administered as placebo
Overall Number of Participants Analyzed 29 28
Least Squares Mean (Standard Error)
Unit of Measure: ng/ml
-0.15  (0.58) 0.88  (0.57)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Carbon Monoxide Inhalation, Oxygen 21%
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.2072
Comments [Not Specified]
Method ANOVA
Comments Repeated measure ANOVA
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -1.04
Parameter Dispersion
Type: Standard Error of the Mean
Value: 0.81
Estimation Comments Difference = (Change from baseline to Week 12 for Carbon monoxide group) minus (Change from baseline to Week 12 for Placebo group)
2.Secondary Outcome
Title Total Lung Capacity % Predicted Values (TLC)
Hide Description 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
Time Frame Baseline to Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Carbon Monoxide Inhalation Oxygen 21%
Hide Arm/Group Description:

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.

Oxygen: Room air oxygen concentrations will be administered as placebo
Overall Number of Participants Analyzed 29 29
Least Squares Mean (Standard Error)
Unit of Measure: % Predicted
-2.29  (1.12) -1.44  (1.10)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Carbon Monoxide Inhalation, Oxygen 21%
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.5882
Comments [Not Specified]
Method ANOVA
Comments Repeated Measure ANOVA
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.85
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.57
Estimation Comments Difference = (Change from baseline to week 12 for CO group) minus (Change from baseline to week 12 for placebo group)
3.Secondary Outcome
Title Diffusing Capacity for Carbon Monoxide (DLCO) % Predicted Values
Hide Description 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
Time Frame Baseline to Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Carbon Monoxide Inhalation Oxygen 21%
Hide Arm/Group Description:

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.

Oxygen: Room air oxygen concentrations will be administered as placebo
Overall Number of Participants Analyzed 29 29
Least Squares Mean (Standard Error)
Unit of Measure: % predicted
1.10  (1.41) 0.46  (1.32)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Carbon Monoxide Inhalation, Oxygen 21%
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.7401
Comments [Not Specified]
Method ANOVA
Comments Repeated Measure ANOVA
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value 0.64
Parameter Dispersion
Type: Standard Error of the Mean
Value: 1.93
Estimation Comments difference=(change from baseline to week 12 for CO group) minus (change from baseline to week 12 for placebo group)
4.Secondary Outcome
Title Six Minute Walk Distance
Hide Description 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
Time Frame Baseline to Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Carbon Monoxide Inhalation Oxygen 21%
Hide Arm/Group Description:

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.

Oxygen: Room air oxygen concentrations will be administered as placebo
Overall Number of Participants Analyzed 29 29
Least Squares Mean (Standard Error)
Unit of Measure: meters
-35.54  (12.83) 12.92  (12.83)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Carbon Monoxide Inhalation, Oxygen 21%
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.0099
Comments [Not Specified]
Method ANOVA
Comments Repeated measure ANOVA
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -48.46
Parameter Dispersion
Type: Standard Error of the Mean
Value: 18.14
Estimation Comments Difference=(Change from baseline to week 12 for CO group) minus (Change from baseline to week 12 for placebo group)
5.Secondary Outcome
Title St George's Respiratory Questionnaire
Hide Description 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.
Time Frame Baseline to Week 12
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Carbon Monoxide Inhalation Oxygen 21%
Hide Arm/Group Description:

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.

Oxygen: Room air oxygen concentrations will be administered as placebo
Overall Number of Participants Analyzed 29 29
Least Squares Mean (Standard Error)
Unit of Measure: Total Score
-2.12  (1.70) -1.55  (1.72)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Carbon Monoxide Inhalation, Oxygen 21%
Comments [Not Specified]
Type of Statistical Test Superiority
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.8124
Comments [Not Specified]
Method ANOVA
Comments Repeated measure ANOVA
Method of Estimation Estimation Parameter Mean Difference (Net)
Estimated Value -0.58
Parameter Dispersion
Type: Standard Error of the Mean
Value: 2.42
Estimation Comments [Not Specified]
Time Frame Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Carbon Monoxide Inhalation Oxygen 21%
Hide Arm/Group Description

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.

Oxygen: Room air oxygen concentrations will be administered as placebo
All-Cause Mortality
Carbon Monoxide Inhalation Oxygen 21%
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Carbon Monoxide Inhalation Oxygen 21%
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   3/29 (10.34%)      7/29 (24.14%)    
Cardiac disorders     
Acute Coronary Syndrome  1  0/29 (0.00%)  0 1/29 (3.45%)  1
Gastrointestinal disorders     
Acute pancreatitis  1  0/29 (0.00%)  0 1/29 (3.45%)  2
Worsening Cirrhosis  1  0/29 (0.00%)  0 1/29 (3.45%)  1
Colonic Obstruction  1  1/29 (3.45%)  1 0/29 (0.00%)  0
Infections and infestations     
Pneumonia  1  0/29 (0.00%)  0 2/29 (6.90%)  2
Neoplasms benign, malignant and unspecified (incl cysts and polyps)     
Acute syndrome of innapropriate antidiuretic hormone (SIADH)  1  1/29 (3.45%)  2 0/29 (0.00%)  0
Small Cell Cancer  1  1/29 (3.45%)  1 0/29 (0.00%)  0
Respiratory, thoracic and mediastinal disorders     
IPF progression  1  1/29 (3.45%)  1 2/29 (6.90%)  2
Pneumothorax  1  1/29 (3.45%)  1 0/29 (0.00%)  0
Worsening of Shortness of Breath  1  1/29 (3.45%)  1 1/29 (3.45%)  1
Pulmonary Fibrosis Related Death  1  0/29 (0.00%)  0 1/29 (3.45%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Carbon Monoxide Inhalation Oxygen 21%
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   28/29 (96.55%)      19/29 (65.52%)    
Gastrointestinal disorders     
Diarrhea  1  2/29 (6.90%)  4 2/29 (6.90%)  3
Gastroesophageal reflux disease  1  3/29 (10.34%)  4 2/29 (6.90%)  3
General disorders     
Fatigue  1  0/29 (0.00%)  0 3/29 (10.34%)  3
Infections and infestations     
Upper respiratory tract infection  1  3/29 (10.34%)  4 5/29 (17.24%)  5
Nervous system disorders     
Dizziness  1  3/29 (10.34%)  3 3/29 (10.34%)  3
Headache  1  5/29 (17.24%)  6 8/29 (27.59%)  9
Respiratory, thoracic and mediastinal disorders     
Cough  1  4/29 (13.79%)  4 7/29 (24.14%)  9
Dyspnea  1  14/29 (48.28%)  16 8/29 (27.59%)  10
Nasal Congestion  1 [1]  3/29 (10.34%)  5 4/29 (13.79%)  5
Productive Cough  1  5/29 (17.24%)  5 3/29 (10.34%)  5
Wheezing  1  0/29 (0.00%)  0 2/29 (6.90%)  3
Indicates events were collected by systematic assessment
1
Term from vocabulary, CTCAE (4.0)
[1]
Common Cold symptom
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Ivan Rosas, MD
Organization: Brigham and Women's Hospital
Phone: 617-278-0434
Responsible Party: Ivan O. Rosas, Brigham and Women's Hospital
ClinicalTrials.gov Identifier: NCT01214187     History of Changes
Other Study ID Numbers: 1U01HL105371 ( U.S. NIH Grant/Contract )
1U01HL105371 ( U.S. NIH Grant/Contract )
First Submitted: September 30, 2010
First Posted: October 4, 2010
Results First Submitted: March 1, 2017
Results First Posted: June 14, 2017
Last Update Posted: June 14, 2017