Clinical trial NCT00122694: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Pulmonary Disease, Chronic Obstructive
Keywords: carbon monoxide
COPD
inflammation
sputum induction
stable COPD
Lead sponsor: Groningen Research Institute for Asthma and COPD
Sponsor class: OTHER
Collaborators: name: Stichting Astma Bestrijding, The Netherlands
First posted: 2005-07-22
Enrollment: 20
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: percentage of neutrophils in induced sputum
Secondary outcomes:
measure: methacholine provocation threshold
measure: exhaled CO/NO
measure: FEV1, FVC, RAW, sgaw
measure: inflammatory parameters in sputum and blood
measure: 8-isoprostane in exhaled breath
Other outcomes:
Locations:
city: Groningen
country: Netherlands
facility: University Medical Center Groningen, Department of Pulmonary Diseases
Study officials:
affiliation: University Medical Center Groningen, Department of Pulmonary Diseases
name: H AM Kerstjens, Prof., MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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. doi: 10.1183/09031936.00163206. Epub 2007 Aug 22.