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

Study Overview
=================
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.

Official Title
-----------------
A Double Blind, Crossover Placebo-controlled Study to Evaluate the Effect of L-arginine and Aminoguanidine on Bronchial and Alveolar Nitric Oxide and Nitric Oxide Metabolites

Conditions
-----------------
Chronic Obstructive Pulmonary Disease

Intervention / Treatment
-----------------
* Drug: Aminoguanidine
* Drug: Placebos


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy volunteers non smoker<br>Control group | Drug: Aminoguanidine<br>* 500mg<br>* Other names: Nebulased Aminoguanidine;Drug: Placebos<br>* 2ml<br>* Other names: Nebulase saline solution;|
| Experimental: Healthy volunteers smoker<br>More than 10 pack-years | Drug: Aminoguanidine<br>* 500mg<br>* Other names: Nebulased Aminoguanidine;Drug: Placebos<br>* 2ml<br>* Other names: Nebulase saline solution;|
| Experimental: Chronic Obstructive Pulmonary Disease COPD<br>COPD diagnosed according to the Global Initiative for Chronic Obstructive Lung Disease guidelines | Drug: Aminoguanidine<br>* 500mg<br>* Other names: Nebulased Aminoguanidine;Drug: Placebos<br>* 2ml<br>* Other names: Nebulase saline solution;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bronchial exhale nitric oxide (JNO) | Bronchial exhale nitric oxide (JNO) as assessed by Chemo luminescence | 24 hours | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
COPD, Aminoguanidine, Nitric oxide