Carbon Monoxide to Prevent Lung Inflammation

NCT00094406 | Completed Phase 1

• 2 other identifiers: 05001205-CC-0012
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

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. ...

Conditions

Respiratory Distress Syndrome, Adult

Keywords

Lung Permeability; Endotoxin Tolerance; Bronchoscopy; Carbon Monoxide Inhalation

Interventions

Bronchoscopy PROCEDURE

Bronchoalveolar lavage PROCEDURE

Endotoxin DRUG

Carbon Monoxide DRUG

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may not qualify if:

• Normal screening examination including:
• medical history and physical examination, nonsmoker, no concurrent medications including aspirin or nonsteroidal anti-inflammatory drugs, no active medical problems
• complete blood count with differential and platelet counts
• serum chemistries including creatinine, blood urea nitrogen, glucose, liver enzymes and function tests, electrolytes, prothrombin time, partial thromboplastin time, carboxyhemoglobin measured by venous co-oxymetry.
• urinalysis
• female subjects must have negative urine pregnancy test within one week of participation (this will be repeated immediately prior to beginning the screening procedures due to radiation exposure from the chest x-ray)
• electrocardiogram
• chest radiograph
• Sexually active females not using contraceptive methods will be instructed to abstain from sexual activity or use barrier contraception methods from the time of last negative pregnancy test to 24 hours after completion of the study.
• active tobacco use
• baseline caroxyhemoglobin greater than 2%
• pregnancy
• lactation
• medical history of recent clinically significant asthma allergy to both sulfa- and penicillin-based drugs
• Allergy to both sulfa- and penicillin-based drugs.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (4)

• Hudson LD, Milberg JA, Anardi D, Maunder RJ. Clinical risks for development of the acute respiratory distress syndrome. Am J Respir Crit Care Med. 1995 Feb;151(2 Pt 1):293-301. doi: 10.1164/ajrccm.151.2.7842182.

  PMID: 7842182 BACKGROUND

• Baumann WR, Jung RC, Koss M, Boylen CT, Navarro L, Sharma OP. Incidence and mortality of adult respiratory distress syndrome: a prospective analysis from a large metropolitan hospital. Crit Care Med. 1986 Jan;14(1):1-4. doi: 10.1097/00003246-198601000-00001.

  PMID: 3484443 BACKGROUND

• Milberg JA, Davis DR, Steinberg KP, Hudson LD. Improved survival of patients with acute respiratory distress syndrome (ARDS): 1983-1993. JAMA. 1995 Jan 25;273(4):306-9.

  PMID: 7815658 BACKGROUND

• Zhang T, Zhang G, Chen X, Chen Z, Tan AY, Lin A, Zhang C, Torres LK, Bajrami S, Zhang T, Zhang G, Xiang JZ, Hissong EM, Chen YT, Li Y, Du YN. Low-dose carbon monoxide suppresses metastatic progression of disseminated cancer cells. Cancer Lett. 2022 Oct 10;546:215831. doi: 10.1016/j.canlet.2022.215831. Epub 2022 Jul 19.

  PMID: 35868533 DERIVED

MeSH Terms

Conditions

Respiratory Distress Syndrome

Interventions

Bronchoscopy; Bronchoalveolar Lavage; Endotoxins; Carbon Monoxide

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures; Therapeutic Irrigation; Investigative Techniques; Bacterial Toxins; Toxins, Biological; Biological Factors; Carbon Compounds, Inorganic; Inorganic Chemicals; Gases; Oxides; Oxygen Compounds

Study Officials

• Anthony F Suffredini, M.D.

  National Institutes of Health Clinical Center (CC)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 16, 2004
• First Posted: October 18, 2004
• Study Start: October 13, 2004
• Primary Completion: March 11, 2010
• Study Completion: March 11, 2010
• Last Updated: December 17, 2019

Record last verified: 2016-04-19

Locations

US (1)