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

NCT ID: NCT00159380

Last Updated: 2019-07-10

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-09-30
• Study Completion Date: 2005-03-31

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.

Conditions

Asthma

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Healthy volunteers

8 non smokers non asthmatic

Group Type: EXPERIMENTAL

Placebos

Intervention Type: DRUG

2ml

Asthma volunteers

8 asthmatic mild

Group Type: EXPERIMENTAL

Aminoguanidine

Intervention Type: DRUG

500mg

Interventions

Aminoguanidine

500mg

Intervention Type: DRUG

Placebos

2ml

Intervention Type: DRUG

Other Intervention Names

Inhalation of aminoguanidine; Nebulase saline solution

Eligibility Criteria

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

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sergei A Kharitonov, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

Section of Airway Disease, Asthma Lab, Imperial College London, Royal Brompton Hospital

London, , United Kingdom

Countries

United Kingdom

References

Brindicci C, Ito K, Barnes PJ, Kharitonov SA. Effect of an inducible nitric oxide synthase inhibitor on differential flow-exhaled nitric oxide in asthmatic patients and healthy volunteers. Chest. 2007 Aug;132(2):581-8. doi: 10.1378/chest.06-3046. Epub 2007 Jun 5.

Reference Type: RESULT

PMID: 17550932 (View on PubMed)

Other Identifiers

2002AT033B

Identifier Type: -

Identifier Source: org_study_id