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

Imperial College London

Status: Completed

Conditions: Chronic Obstructive Pulmonary Disease

Treatments: Drug: Placebos; Drug: Aminoguanidine

Study type: Interventional

Funder types: Other

Identifiers

NCT00180635

02-104-170903

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 21 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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30 participants in 3 patient groups

Healthy volunteers non smoker

Experimental group

Description:

Control group

Treatment:

Drug: Aminoguanidine

Drug: Placebos

Healthy volunteers smoker

Experimental group

Description:

More than 10 pack-years

Treatment:

Drug: Aminoguanidine

Drug: Placebos

Chronic Obstructive Pulmonary Disease COPD

Experimental group

Description:

COPD diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease guidelines

Treatment:

Drug: Aminoguanidine

Drug: Placebos