Nitric Oxide (NO) Donors and Inhibitors Study: Study to Evaluate L-Arginine and Aminoguanidine in Asthmatic Subjects

Not Applicable

Completed

• Conditions: Asthma
• Interventions: Drug: Placebos; Drug: Aminoguanidine

• Registration Number: NCT00159380
• 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, saliva and nasal lavage fluid in normal and asthmatic subjects.

Detailed Description

Nitric oxide (NO) is produced by a variety of cells within the respiratory tract, particularly airway epithelial cells, and its increased concentration in asthma is likely to derive from inducible NO synthase (iNOS) expressed in inflamed airways. To evaluate whether an increased bronchial flux of NO (ie, airway wall NO flux \[Jno\] in picoliters per second) produced in the large airways is due to an enzyme overexpression, we administered a relatively selective iNOS inhibitor, aminoguanidine, by nebulization in a double-blind, placebo-controlled manner in asthmatic and healthy subjects and also investigated whether the same concentration of inhibitor has any effect on NO produced in the peripheral lungs (ie, alveolar NO concentration \[Calv\] in parts per billion \[ppb\]) or on the diffusing capacity of NO (Dno) \[in picoliters per second-1 per ppb-1) in the airways. Aminoguanidine administration resulted in a significant reduction in Jno compared with administration of the saline solution control in eight healthy subjects and in eight patients with asthma but caused no significant changes in Calv or in Dno in either group.

Study Timeline

• Study Start: 2003-09
• Primary Completion: 2005-03
• Study Completion: 2005-03
• Study First Submitted: 2005-09-09
• Study First Submitted QC: 2005-09-09
• Study First Posted: 2005-09-12
• Status Verified: 2019-07
• Last Update Submitted: 2019-07-09
• Last Update Posted: 2019-07-10

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 16

Inclusion Criteria

Healthy non-smokers (n=10):

• Nonatopic subjects (exhaled NO greater than or equal to 10 ppb; flow 50 ml/s)
• Normal spirometry
• Able to comprehend and grant a written informed consent

Asthmatic subjects (n=15):

• Forced expiratory volume in one second (FEV1) of no less than 70% of predicted (exhaled NO greater than or equal to 15 ppb; flow 50 ml/s)
• Clinically stable (steroid-naïve or taking no > 600 mcg/day of inhaled steroids)
• Able to comprehend and grant a written informed consent

Exclusion Criteria

• Currently smoking
• Any lung disease other than asthma which may interfere with the study
• 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
Healthy volunteers	Placebos	8 non smokers non asthmatic
Asthma volunteers	Aminoguanidine	8 asthmatic mild

Primary Outcome Measures

Name	Time	Method
Bronchial exhale nitric oxide	6 hours	Bronchial exhale nitric oxide (JNo) assessed by chemo luminescence
Peripheral exhaled nitric oxide	6 hours	Peripheral exhaled nitric oxide(CALV) assessed by chemo luminescence

Trial Locations

Locations (1)

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