NCT00094406

Carbon Monoxide to Prevent Lung Inflammation

Completed Phase 1 Last updated 17 December 2019

What this trial tests

Phase 1 trial testing Bronchoscopy in Respiratory Distress Syndrome, Adult in 35 participants. Completed in 11 March 2010.

Timeline

13 October 2004

Primary endpoint
11 March 2010

11 March 2010

Quick facts

Lead sponsor	National Institutes of Health Clinical Center (CC)
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Primary purpose	treatment
Enrollment	35
Start date	13 October 2004
Primary completion	11 March 2010
Estimated completion	11 March 2010
Sites	1 location across United States

Drugs / interventions tested

• Bronchoscopy
• Bronchoalveolar lavage — full drug profile →
• Endotoxin — full drug profile →
• Carbon Monoxide — full drug profile →

Conditions studied

• Respiratory Distress Syndrome, Adult — all drugs for Respiratory Distress Syndrome, Adult →

Sponsor

National Institutes of Health Clinical Center (CC)

Who can join

Adults 18 to 40, any sex, with Respiratory Distress Syndrome, Adult. Patients with the condition only — healthy volunteers not accepted.

Sponsor's own description

This study will examine in healthy volunteers how breathing carbon monoxide (CO) affects lung inflammation. Severe lung inflammation sometimes develops in patients with pneumonia or patients who develop serious blood stream infections. Studies in the laboratory and in animals show that CO can decrease lung inflammation.

Healthy volunteers between 18 and 40 years of age who do not smoke, are not taking any medications, do not have asthma, are not allergic to sulfa- and penicillin-based drugs, and are not pregnant may be eligible for this study. Candidates are screened with a medical history and physical examination, blood and urine tests, electrocardiogram (EKG), and chest x-ray. Subjects are enrolled in either a pilot study or the main study.

Participants undergo bronchoscopy and bronchoalveolar lavage to study the effects of endotoxin (a component of bacteria that causes inflammation similar to that in patients with lung infections) on lung function. Before the procedure, a small plastic tube (catheter) is placed in a vein to collect blood samples and another is placed in an artery to check blood pressure. For the bronchoscopy, the mouth and nasal airways are numbed with lidocaine, and a bronchoscope (thin flexible tube) is passed through the nose into the airways of the lung. A small amount of salt water is squirted through the bronchoscope into one lung and then salt water containing endotoxin is squirted into the other lung.

Following the bronchoscopy, subjects are treated with either CO or room air (placebo) for 6 hours. (Subjects in the pilot study receive treatment for only 3 hours). The gas is delivered through a cushioned mask placed over the nose and mouth. The amount of exhaled CO is measured before, during, and after inhalation of the gas. For this measurement, subjects take a deep breath to fill up their lungs and slowly exhale into a mouthpiece connected to a measuring device until they feel their lungs are empty.

After the CO treatment, a second bronchoscopy is done to examine how the lung responded to the CO or room air. This is studied in two ways. To sample the air, a large needle is used to withdraw air through the bronchoscope over about 3 seconds. Then the areas of the lung that were squirted with salt water alone and with endotoxin and salt water and are rinsed (lavage) and cells and secretions are collected.

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Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Heme Oxygenases in Cardiovascular Health and Disease.
   Ayer A, Zarjou A, Agarwal A, Stocker R. · · 2016 · cited 179× · PMID 27604527 · DOI 10.1152/physrev.00003.2016
2. New insights into intracellular locations and functions of heme oxygenase-1.
   Dunn LL, Midwinter RG, Ni J, Hamid HA, et al · · 2014 · cited 138× · PMID 24180287 · DOI 10.1089/ars.2013.5675
3. Evolution of novel small-molecule therapeutics targeting sickle cell vasculopathy.
   Kato GJ, Gladwin MT. · · 2008 · cited 59× · PMID 19066384 · DOI 10.1001/jama.2008.598
4. Carbon Monoxide: from Poison to Clinical Trials.
   Siracusa R, Schaufler A, Calabrese V, Fuller PM, et al · · 2021 · cited 57× · PMID 33781582 · DOI 10.1016/j.tips.2021.02.003
5. Proximal tubule-targeted heme oxygenase-1 in cisplatin-induced acute kidney injury.
   Bolisetty S, Traylor A, Joseph R, Zarjou A, et al · · 2016 · cited 56× · PMID 26672618 · DOI 10.1152/ajprenal.00335.2015
6. Therapeutic Aspects of Carbon Monoxide in Cardiovascular Disease.
   Kim HH, Choi S. · · 2018 · cited 55× · PMID 30104479 · DOI 10.3390/ijms19082381
7. Reduced caveolin-1 promotes hyperinflammation due to abnormal heme oxygenase-1 localization in lipopolysaccharide-challenged macrophages with dysfunctional cystic fibrosis transmembrane conductance regulator.
   Zhang PX, Murray TS, Villella VR, Ferrari E, et al · · 2013 · cited 43× · PMID 23606537 · DOI 10.4049/jimmunol.1201607
8. The carbon monoxide releasing molecule CORM-2 attenuates Pseudomonas aeruginosa biofilm formation.
   Murray TS, Okegbe C, Gao Y, Kazmierczak BI, et al · · 2012 · cited 40× · PMID 22563385 · DOI 10.1371/journal.pone.0035499