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

July 9, 2019 updated by: Imperial College London

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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 Type

Interventional

Enrollment (Actual)

16

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United Kingdom
      • London, United Kingdom, SW3 6LY
        • Section of Airway Disease, Asthma Lab, Imperial College London, Royal Brompton Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Bronchial exhale nitric oxide
Time Frame: 6 hours
Bronchial exhale nitric oxide (JNo) assessed by chemo luminescence
6 hours
Peripheral exhaled nitric oxide
Time Frame: 6 hours
Peripheral exhaled nitric oxide(CALV) assessed by chemo luminescence
6 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Imperial College London

Investigators

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

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 1, 2003

Primary Completion (Actual)

March 1, 2005

Study Completion (Actual)

March 1, 2005

Study Registration Dates

First Submitted

September 9, 2005

First Submitted That Met QC Criteria

September 9, 2005

First Posted (Estimate)

September 12, 2005

Study Record Updates

Last Update Posted (Actual)

July 10, 2019

Last Update Submitted That Met QC Criteria

July 9, 2019

Last Verified

July 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2002AT033B

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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