Modification of Chronic Inflammation by Inhaled Carbon Monoxide in Patients With Stable Chronic Obstructive Pulmonary Disease (COPD)

• ClinicalTrials.gov Identifier: NCT00122694
• Recruitment Status: Completed
• First Posted: July 22, 2005
• Last Update Posted: September 12, 2006
• Sponsor: Groningen Research Institute for Asthma and COPD
• Collaborator: Stichting Astma Bestrijding, The Netherlands
• Information provided by: Groningen Research Institute for Asthma and COPD

Tracking Information

• First Submitted Date: July 21, 2005
• First Posted Date: July 22, 2005
• Last Update Posted Date: September 12, 2006
• Study Start Date: January 2005
• Primary Completion Date: Not Provided
• Current Primary Outcome Measures (submitted: July 28, 2005): percentage of neutrophils in induced sputum
• Original Primary Outcome Measures (submitted: July 21, 2005):  neutrophils in induced sputum.

Current Secondary Outcome Measures (submitted: July 28, 2005)

• methacholine provocation threshold
• exhaled CO/NO
• FEV1, FVC, RAW, sgaw
• inflammatory parameters in sputum and blood
• 8-isoprostane in exhaled breath

Original Secondary Outcome Measures (submitted: July 21, 2005)

• metacholine provocation treshold
• exhaled CO/NO
• FEV1, FVC, RAW,sgaw
• inflammatory parameters in sputum and blood
• 8-isoprostane in exhaled breath

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Modification of Chronic Inflammation by Inhaled Carbon Monoxide in Patients With Stable Chronic Obstructive Pulmonary Disease (COPD)
• Official Title: Modification of Chronic Inflammation by Inhaled Carbon Monoxide in Patients With Stable COPD
• Brief Summary: The purpose of this study is to determine whether carbon monoxide is effective in the treatment of stable COPD.

Detailed Description

COPD is characterised by a chronic pulmonary inflammation and a shifted oxidant/antioxidant balance. The main cause of this inflammation is smoking. After smoking cessation, this inflammation and shifted oxidant/antioxidant balance continues. This causes an increased deterioration of lung function compared to healthy persons of matching age.

The ongoing inflammation appears to be relatively insensitive to corticosteroid therapy.

Until now, there is no therapy for this inflammation. Both in vitro and in vivo studies show that carbon monoxide has, besides an antioxidant capacity, anti-inflammatory properties. The aim of this trial is to study whether the inflammation can be reduced by inhalation of carbon monoxide.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: Double; Primary Purpose: Treatment
• Condition: Pulmonary Disease, Chronic Obstructive
• Intervention: Drug: carbon monoxide
• Study Arms: Not Provided
• Publications *: Bathoorn E, Slebos DJ, Postma DS, Koeter GH, van Oosterhout AJ, van der Toorn M, Boezen HM, Kerstjens HA. Anti-inflammatory effects of inhaled carbon monoxide in patients with COPD: a pilot study. Eur Respir J. 2007 Dec;30(6):1131-7. Epub 2007 Aug 22.

Recruitment Information

• Recruitment Status: Completed
• Enrollment (submitted: July 21, 2005): 20
• Original Enrollment: Same as current
• Study Completion Date: March 2006
• Primary Completion Date: Not Provided

Eligibility Criteria

Inclusion Criteria:

• Men and women, age > 40 years. Women must be post-menopausal (i.e. at least one year must have passed after the last menstruation), surgically sterile or using acceptable contraceptives, as judged by the investigator.
• A diagnosis of COPD according to the criteria of the American Thoracic Society (ATS); a disease state characterised by the presence of chronic airway obstruction due to chronic bronchitis (cough/sputum on most days a week for 3 months a year for at least two successive years); or emphysema.
• FEV1 > 0.7 litres
• FEV1/FVC ratio < 70% (equation retrieval system [ERS] equations)
• A smoking history of > 10 pack years
• Completely stopped smoking > 1 year ago
• No upper or lower respiratory tract infection in the last 4 weeks
• In a stable phase of COPD, as judged by the investigator
• Signed and dated informed consent obtained before any study related procedures (including withdrawal of concomitant medication) are conducted

Exclusion Criteria:

• Treatment with immune-modulating agents for any other disease
• History of asthma; former diagnosis of asthma
• Arterial oxygen tension (PaO2) < 8.0 kPa
• Any significant other pulmonary disease or disorder (e.g. alpha1-antitrypsin deficiency, bronchiectasies), as judged by the investigator
• Patients with other significant disease or disorder (like cardiovascular, gastrointestinal, liver, renal, neurological, musculoskeletal, endocrine, metabolic [including diagnosed diabetes], malignant, psychiatric, major physical impairment), which, in the opinion of the investigator may either put the patient at risk because of participation in the study; or may influence the results of the study, or the patient's ability to participate in the study.
• Patients unable to blow reproducable lung function measurements
• Patients using medicine with anti-oxidant character like n-acetyl-cysteine.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT00122694
• Other Study ID Numbers: METc2003.249; SAB 2004/024
• Has Data Monitoring Committee: Not Provided
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Not Provided
• Study Sponsor: Groningen Research Institute for Asthma and COPD
• Collaborators: Stichting Astma Bestrijding, The Netherlands

Investigators

• Principal Investigator: H AM Kerstjens, Prof., MD, PhD; University Medical Center Groningen, Department of Pulmonary Diseases

• PRS Account: Groningen Research Institute for Asthma and COPD
• Verification Date: July 2006