ClinicalTrials.gg
Sign In
CompletedNCT01214187Updated Jun 14, 2017Results posted

Study of Inhaled Carbon Monoxide to Treat Idiopathic Pulmonary Fibrosis

A Phase 2 interventional study of inhaled carbon monoxide and Oxygen in Idiopathic Pulmonary Fibrosis, sponsored by Brigham and Women's Hospital. Completed at 8 sites in United States. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2017-06-14.

Sponsored by Brigham and Women's Hospital · Phase 2, Interventional, and Treatment

Phase
Phase 2
Study type
Interventional
Enrollment
58
Allocation
Randomized
Ages
18 Years to 85 Years
Sex
All
01

Study summary

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

Read the 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.

02

Conditions studied

  • Idiopathic Pulmonary Fibrosis

Keywords

  • idiopathic pulmonary fibrosis
  • IPF
  • pulmonary fibrosis
  • carbon monoxide
03

In context

Idiopathic Pulmonary Fibrosis

565 studies on the registry are indexed under Idiopathic Pulmonary Fibrosis; 117 are open to participants now.

This study's enrollment of 58 is close to the median of 55 across 388 interventional studies indexed under Idiopathic Pulmonary Fibrosis.

Browse Idiopathic Pulmonary Fibrosis studies →

Lead sponsor

Brigham and Women's Hospital is the lead sponsor of 1,263 studies on the registry; 225 are open to participants now.

Of its 116 completed or terminated interventional studies of FDA-regulated products, 65 (56%) have results posted.

Browse Brigham and Women's Hospital studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years to 85 Years
Sexes eligible
All
Accepts healthy volunteers
No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

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
05

Study design

Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
Double (Participant, Care provider)
Enrollment
58 participants (actual)

Study arms

  • 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

  • Placebo comparator
    Oxygen 21%

    Other: Oxygen

Interventions

  • Druginhaled 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.

    Also known as: CO

  • OtherOxygen

    Room air oxygen concentrations will be administered as placebo

    Also known as: O2

06

What researchers measure

Primary outcomes

  1. 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.

    Time frame: Baseline to Week 12

Secondary outcomes

  1. 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

    Time frame: Baseline to Week 12

  2. 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

    Time frame: Baseline to Week 12

  3. 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

    Time frame: Baseline to Week 12

  4. 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.

    Time frame: Baseline to Week 12

07

Results

Posted Jun 14, 2017

Participant flow

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.

Participant flow — Overall Study
MilestoneCarbon Monoxide InhalationOxygen 21%
Started2929
Completed2223
Not completed76
Withdrew: Adverse event62
Withdrew: Death11
Withdrew: Withdrawal by subject03

Outcome measures

PrimarySerum 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.

Time frame:
Baseline to Week 12
Reported as:
Least squares mean · ng/ml
Serum MMP7 Level
ng/mlCarbon Monoxide InhalationOxygen 21%
Serum MMP7 Level-0.15 ± 0.580.88 ± 0.57
Statistical analysis
  • Carbon Monoxide Inhalation vs Oxygen 21% · ANOVA · p = 0.2072 · Mean difference (net): -1.04Difference = (Change from baseline to Week 12 for Carbon monoxide group) minus (Change from baseline to Week 12 for Placebo group)
SecondaryTotal 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

Time frame:
Baseline to Week 12
Reported as:
Least squares mean · % Predicted
Total Lung Capacity % Predicted Values (TLC)
% PredictedCarbon Monoxide InhalationOxygen 21%
Total Lung Capacity % Predicted Values (TLC)-2.29 ± 1.12-1.44 ± 1.10
Statistical analysis
  • Carbon Monoxide Inhalation vs Oxygen 21% · ANOVA · p = 0.5882 · Mean difference (net): -0.85Difference = (Change from baseline to week 12 for CO group) minus (Change from baseline to week 12 for placebo group)
SecondaryDiffusing 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

Time frame:
Baseline to Week 12
Reported as:
Least squares mean · % predicted
Diffusing Capacity for Carbon Monoxide (DLCO) % Predicted Values
% predictedCarbon Monoxide InhalationOxygen 21%
Diffusing Capacity for Carbon Monoxide (DLCO) % Predicted Values1.10 ± 1.410.46 ± 1.32
Statistical analysis
  • Carbon Monoxide Inhalation vs Oxygen 21% · ANOVA · p = 0.7401 · Mean difference (net): 0.64difference=(change from baseline to week 12 for CO group) minus (change from baseline to week 12 for placebo group)
SecondarySix 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

Time frame:
Baseline to Week 12
Reported as:
Least squares mean · meters
Six Minute Walk Distance
metersCarbon Monoxide InhalationOxygen 21%
Six Minute Walk Distance-35.54 ± 12.8312.92 ± 12.83
Statistical analysis
  • Carbon Monoxide Inhalation vs Oxygen 21% · ANOVA · p = 0.0099 · Mean difference (net): -48.46Difference=(Change from baseline to week 12 for CO group) minus (Change from baseline to week 12 for placebo group)
SecondarySt 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.

Time frame:
Baseline to Week 12
Reported as:
Least squares mean · Total Score
St George's Respiratory Questionnaire
Total ScoreCarbon Monoxide InhalationOxygen 21%
St George's Respiratory Questionnaire-2.12 ± 1.70-1.55 ± 1.72
Statistical analysis
  • Carbon Monoxide Inhalation vs Oxygen 21% · ANOVA · p = 0.8124 · Mean difference (net): -0.58Repeated measure ANOVA

Adverse events

Collected over Adverse Events were collected from the start of treatment through 28 days after discontinuation of the study.. Non-serious events are listed at a 5% frequency threshold.

Adverse event summary by group
GroupDeathsSeriousOther
Carbon Monoxide Inhalation—3/29 (10.3%)28/29 (96.6%)
Oxygen 21%—7/29 (24.1%)19/29 (65.5%)
Most frequent serious events
Showing 10 of 11
Most frequent serious events
EventCarbon Monoxide InhalationOxygen 21%
PneumoniaInfections and infestations0/292/29
IPF progressionRespiratory, thoracic and mediastinal disorders1/292/29
Acute pancreatitisGastrointestinal disorders0/291/29
Acute Coronary SyndromeCardiac disorders0/291/29
Worsening CirrhosisGastrointestinal disorders0/291/29
Colonic ObstructionGastrointestinal disorders1/290/29
Acute syndrome of innapropriate antidiuretic hormone (SIADH)Neoplasms benign, malignant and unspecified (incl cysts and polyps)1/290/29
PneumothoraxRespiratory, thoracic and mediastinal disorders1/290/29
Small Cell CancerNeoplasms benign, malignant and unspecified (incl cysts and polyps)1/290/29
Worsening of Shortness of BreathRespiratory, thoracic and mediastinal disorders1/291/29
Most frequent other events
Showing 10 of 11
Most frequent other events
EventCarbon Monoxide InhalationOxygen 21%
DyspneaRespiratory, thoracic and mediastinal disorders14/298/29
HeadacheNervous system disorders5/298/29
CoughRespiratory, thoracic and mediastinal disorders4/297/29
Productive CoughRespiratory, thoracic and mediastinal disorders5/293/29
Upper respiratory tract infectionInfections and infestations3/295/29
Nasal CongestionRespiratory, thoracic and mediastinal disorders3/294/29
DizzinessNervous system disorders3/293/29
Gastroesophageal reflux diseaseGastrointestinal disorders3/292/29
FatigueGeneral disorders0/293/29
DiarrheaGastrointestinal disorders2/292/29

Baseline characteristics

Age, Continuous
Age, Continuous(years)Carbon Monoxide InhalationOxygen 21%Total
Mean66.6 ± 6.168.6 ± 8.468 ± 7
Sex: Female, Male
Sex: Female, Male(Participants)Carbon Monoxide InhalationOxygen 21%Total
Female4711
Male252247
Ethnicity (NIH/OMB)
Ethnicity (NIH/OMB)(Participants)Carbon Monoxide InhalationOxygen 21%Total
Hispanic or Latino123
Not Hispanic or Latino282755
Unknown or Not Reported000
Region of Enrollment
Region of Enrollment(participants)Carbon Monoxide InhalationOxygen 21%Total
United States292958
08

Study locations

8 sites
  • University of California San Francisco
    San Francisco, California 94143, United States
  • University of Illinois Chicago
    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
09

References and documents

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. PubMed 29100885 ↗
10

Timeline

Tracking since Sep 25, 2026
Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Jul 2011, a primary completion of Oct 2014 and a completion of Apr 2015. It does not say whether these dates are actual or estimated.

Results were first posted in Jun 2017, 2 years 8 months after primary completion.

How these figures are worked out, and which studies are left out of them.

Registered
Sep 30, 2010
First posted
Oct 4, 2010
Start
Jul 2011
Primary completionActual
Oct 2014
CompletionActual
Apr 2015
Results first posted
Jun 14, 2017
Last update
Jun 14, 2017
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
No changes since tracking began. The registry record was last updated on Jun 14, 2017, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
11

Registry details

Key details

Study ID
NCT01214187
Lead 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
Responsible party
Ivan O. Rosas (Overall Principle Investigator, Brigham and Women's Hospital) — Principal investigator
First posted
Oct 4, 2010
Start date
Jul 2011
Primary completion
Oct 2014
Completion
Apr 2015
Results posted
Jun 14, 2017
Last update
Jun 14, 2017

Study contacts

Rosas O Ivan, MD
principal investigator · Brigham and Women's Hospital
Joe GN Garcia, MD
principal investigator · University of Illinois at Chicago

Oversight

Data monitoring committee
Yes
View the source record on ClinicalTrials.gov ↗

Not currently enrolling

This study is completed, as verified in May 2017. You cannot join it, but the record below documents what was studied.

Follow this study

Get an email when the registry record changes — status, dates, results — or when someone posts here.

Sign in to follow

Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.

Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drug tested here: Carbon Monoxide

Other studies in this condition

Idiopathic Pulmonary Fibrosis →

Other studies from this sponsor

Brigham and Women's Hospital →

Start the discussion