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

Sponsor
Imperial College London (Other)
Overall Status
Completed
CT.gov ID
NCT00159380
Collaborator
(none)
16
Enrollment
1
Location
2
Arms
18
Actual Duration (Months)
0.9
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
N/A

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 Design

Study Type:
Interventional
Actual Enrollment :
16 participants
Allocation:
Randomized
Intervention Model:
Crossover Assignment
Masking:
Double (Participant, Investigator)
Primary Purpose:
Treatment
Official Title:
A Double Blind, Crossover Placebo-controlled Study to Evaluate the Effect of L-arginine and Aminoguanidine on Bronchial, Alveolar and Nasal NO and NO Metabolites
Actual Study Start Date :
Sep 1, 2003
Actual Primary Completion Date :
Mar 1, 2005
Actual Study Completion Date :
Mar 1, 2005

Arms and Interventions

Arm Intervention/Treatment
Experimental: Healthy volunteers

8 non smokers non asthmatic

Drug: Placebos
2ml
Other Names:
  • Nebulase saline solution

    		•
    Experimental: Asthma volunteers

    8 asthmatic mild

    Drug: Aminoguanidine
    500mg
    Other Names:
  • Inhalation of aminoguanidine

    		•

    Outcome Measures

    Primary Outcome Measures

    1. Bronchial exhale nitric oxide [6 hours]

      Bronchial exhale nitric oxide (JNo) assessed by chemo luminescence

    2. Peripheral exhaled nitric oxide [6 hours]

      Peripheral exhaled nitric oxide(CALV) assessed by chemo luminescence

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    21 Years to 60 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    Yes
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Section of Airway Disease, Asthma Lab, Imperial College London, Royal Brompton Hospital London United Kingdom SW3 6LY

    Sponsors and Collaborators

    • Imperial College London

    Investigators

    • Principal Investigator: Sergei A Kharitonov, MD, PhD, Imperial College London

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Imperial College London
    ClinicalTrials.gov Identifier:
    NCT00159380
    Other Study ID Numbers:
    • 2002AT033B
    First Posted:
    Sep 12, 2005
    Last Update Posted:
    Jul 10, 2019
    Last Verified:
    Jul 1, 2019
    Individual Participant Data (IPD) Sharing Statement:
    No
    Plan to Share IPD:
    No
    Keywords provided by Imperial College London
    Asthma
    Additional relevant MeSH terms:
    Asthma
    Pimagedine

    Study Results

    No Results Posted as of Jul 10, 2019