ATP/AMP Challenge in Healthy Non-smokers, Smokers, Patients With Asthma, and Patients With Chronic Obstructive Pulmonary Disease (COPD)

April 3, 2024 updated by: Imperial College London

Adenosine 5'-Triphosphate (ATP) Challenge in Healthy Non-smokers, Current Smokers and Patients With Mild Asthma and Chronic Obstructive Pulmonary Disease (COPD)

In this randomised, cross-over, controlled study, a total of 84 subjects will be included: 12 healthy non-smoking volunteers; 12 current smokers; 30 patients with mild steroid-naïve asthma; and 30 patients with mild-moderate COPD.

Each subject will have 1 screening visit (if necessary) and 2 study visits. At visits 2 and 3 the effects of adenosine 5'-triphosphate (ATP) or adenosine 5'-monophosphate (AMP) challenge, given in a random order, will be tested.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Background: Extracellular adenosine 5'-triphosphate (ATP) stimulates vagal C and Aδ fibers in the lung, resulting in pronounced bronchoconstriction and cough mediated by P2X2/3 receptors located on vagal sensory nerve terminals. We investigated the effects of nebulized ATP on cough and symptoms in control subjects, healthy smokers, and patients with COPD and compared these responses to the effects of inhaled adenosine, the metabolite of ATP.

Methods: We studied the effects of inhaled ATP and adenosine monophosphate (AMP) on airway caliber, perception of dyspnea assessed by the Borg score, cough sensitivity, and ATP in exhaled breath condensate in healthy nonsmokers (n = 10), healthy smokers (n = 14), and patients with COPD (n = 7).

Results: In comparison with healthy subjects, ATP induced more dyspnea, cough, and throat irritation in smokers and patients with COPD, and the effects of ATP were more pronounced than those of AMP. The concentration of ATP in the exhaled breath condensate of patients with COPD was elevated compared with that of healthy subjects.

Conclusions: Smokers and patients with COPD manifest hypersensitivity to extracellular ATP, which may play a mechanistic role in COPD.

Study Type

Interventional

Enrollment (Actual)

31

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 85 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Healthy non-smokers (n=12)

    • Normal spirometry
    • Forced expiratory volume in 1 second (FEV1) reversibility of < 15% after inhaled beta2-agonists*

  2. At risk (current smokers) (n=12)*

    • Normal spirometry, chronic symptoms (cough, sputum production)
    • FEV1 reversibility of < 15% after inhaled beta2-agonists* (* = Global Strategy for the Diagnosis, Management, and Prevention of COPD)

  3. Mild steroid-naïve asthma (n=30)

    • FEV1 more than or equal to 80%

  4. Mild-moderate COPD (n=30)

    • FEV1 50-80%

Exclusion Criteria:

  1. Pregnancy, breast-feeding, or planned pregnancy during the study.
  2. Fertile women not using acceptable contraceptive measures, as judged by the investigator
  3. Upper respiratory infection within the last 4 weeks
  4. Subjects who have received research medication within the previous one month
  5. Subjects unable to give informed consent
  6. Any psychiatric condition rendering the patient unable to understand the nature, scope, and possible consequences of the study.

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

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Nebulised ATP
Procedure: Inhalation Challenge with ATP
Procedure: Inhalation Challenge with AMP
Active Comparator: Inhaled Adenosine
Procedure: Inhalation Challenge with ATP
Procedure: Inhalation Challenge with AMP

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
PC20 of ATP and AMP
Time Frame: On administration
PC20 of ATP and AMP
On administration
Lung function
Time Frame: On administration
Spirometry
On administration
Borg score
Time Frame: On administration
Measurement of DYSPNEA
On administration
Impulse oscillometry (IOS)
Time Frame: On administration
Small airway function
On administration

Collaborators and Investigators

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

Sponsor

Imperial College London

Collaborators

Duska Scientific Co.

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)

October 1, 2002

Primary Completion (Actual)

October 1, 2004

Study Completion (Actual)

October 1, 2004

Study Registration Dates

First Submitted

September 8, 2005

First Submitted That Met QC Criteria

September 8, 2005

First Posted (Estimated)

September 12, 2005

Study Record Updates

Last Update Posted (Actual)

April 4, 2024

Last Update Submitted That Met QC Criteria

April 3, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • DHTABPT0336

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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