NO Donors and Inhibitors to Study Imbalance of Nitrogen Stress and Antioxidant Defense in COPD

Not Applicable

Completed

• Conditions: Chronic Obstructive Pulmonary Disease
• Interventions: Drug: Aminoguanidine; Drug: Placebos

• Registration Number: NCT00180635
• Lead Sponsor: Imperial College London

Brief Summary

The primary aim of this study is to investigate the effects of oral and inhaled administration of L-arginine and of inhaled aminoguanidine on bronchial and alveolar exhaled NO and NO metabolites in exhaled breath condensate, induced sputum, nasal lavage and mouth wash fluid in healthy non-smokers, current smokers and patients with COPD.

Detailed Description

Nitric oxide (NO) is produced by resident and inflammatory cells in the respiratory tract by the enzyme NO synthase (NOS), which exists in three isoforms: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS. NO production is increased in patients with COPD, and the production of NO under oxidative stress conditions generates reactive nitrogen species that may amplify the inflammatory response in COPD.

Study Timeline

• Study Start: 2003-10
• Study First Submitted: 2005-09-09
• Study First Submitted QC: 2005-09-09
• Study First Posted: 2005-09-16
• Primary Completion: 2006-07
• Study Completion: 2006-07
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-09
• Last Update Posted: 2019-07-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Healthy non-smokers

• Normal spirometry (FEV1 >90 % predicted; exhaled NO bigger than or equal to 10 ppb; flow 50 ml/s)

• At risk (current smokers)

  • Normal spirometry, with or without chronic symptoms (cough, sputum production)
  • FEV1 reversibility of <15% after inhaled beta2-agonists*

• Moderate COPD

  • FEV1 greater than or equal to 30% and < 80%
  • FEV1/FVC < 70% predicted
  • FEV1 reversibility of <15% after inhaled beta2-agonists
  • With or without chronic symptoms (cough, sputum production, dyspnea)

• Able to comprehend and grant a written informed consent

Exclusion Criteria

• Concomitant use or pre-treatment within the last 4 weeks with oral steroids
• Respiratory infection within 4 weeks prior to entry into the trial
• Females who are pregnant or lactating
• History of current or past drug or alcohol abuse

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Chronic Obstructive Pulmonary Disease COPD	Placebos	COPD diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease guidelines
Healthy volunteers smoker	Placebos	More than 10 pack-years
Healthy volunteers non smoker	Placebos	Control group
Healthy volunteers non smoker	Aminoguanidine	Control group
Healthy volunteers smoker	Aminoguanidine	More than 10 pack-years
Chronic Obstructive Pulmonary Disease COPD	Aminoguanidine	COPD diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease guidelines

Primary Outcome Measures

Name	Time	Method
Bronchial exhale nitric oxide (JNO)	24 hours	Bronchial exhale nitric oxide (JNO) as assessed by Chemo luminescence

Trial Locations

Locations (1)

Section of Airway Disease, Asthma Lab, Imperial College London, Royal Brompton Hospital; 🇬🇧 London, United Kingdom