ATP and P2X3 Receptor in Chronic Cough
Neuroinflammatory Interactions of ATP and P2X3 Receptor in the Airways of Chronic Cough Patients: an Exploratory Study
1 other identifier
interventional
20
0 countries
N/A
Brief Summary
This is a laboratory-based study that will be performed at the Clinical Research Centre at the Royal Brompton Hospital,London. The objectives are:
- 1.Determine whether adenosine triphosphate (ATP) is present or released in airways of idiopathic chronic cough patients
- 2.Determine whether there is an increase in cough sensitivity and laryngeal sensitivity to exogenous ATP
- 3.Examine the effects of exogenous ATP on the inflammatory response in the upper and lower airways.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable
Started Feb 2023
Health score is calculated from publicly available data and should be used for screening purposes only.
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Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
January 12, 2023
CompletedFirst Posted
Study publicly available on registry
February 6, 2023
CompletedStudy Start
First participant enrolled
February 28, 2023
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 28, 2024
CompletedStudy Completion
Last participant's last visit for all outcomes
August 31, 2024
CompletedFebruary 6, 2023
January 1, 2023
1.1 years
January 12, 2023
January 26, 2023
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Does ATP inhalation compared to that of saline inhalation change capsaicin cough sensitivity and laryngeal sensitivity?
Capsaicin cough sensitivity will be measured as the concentration of capsaicin causing 2 or 5 coughs, ie C2 or C5 concentrations in micromolar units. Laryngeal sensitivity will be measured as the change in the area of the glottic aperture between expiration and inspiration maneouvre.
18 months
Compare the levels of ATP in bronchoalveolar lavage fluid and in exhaled breath condensate from chronic cough patients to those of non-coughing healthy subjects
This will be done by measurement of ATP concentration in nanomolar units using an off-line luminometer in broncholaveolar lavage fluid and exhaled breath condensate by a paired analysis.
18 months
Secondary Outcomes (2)
Determine the number of coughs and cough frequency after ATP and saline inhalation in chronic cough and in non-coughing participants.
18 months
Does ATP inflammation induce granulocytic inflammation after inhalation of ATP?
18 months.
Study Arms (2)
Effect of saline
PLACEBO COMPARATORSaline will be inhaled from a nebuliser
Effect of ATP
ACTIVE COMPARATORATP solution will be inhaled from a nebuliser
Interventions
ATP and 0.9% saline solution will be inhaled from a nebuliser on separate days, and their effects will be examined.
Coughs are counted for one minute after single-breath inhalations of 0.9% sodium chloride and capsaicin solutions of increasing concentrations (0.98-500 μm) generated from a dosimeter (P.K. Morgan Ltd, Gillingham, UK) set at a dosing period of 1 s. The concentration that caused more than 2 or 5 coughs was recorded as C2 and C5, and the data is analysed as log10 C2 or C5.
All enrolled study participants will be provided with a dedicated Android phone or watch loaded with the Hyfe Research application to monitor and record their cough sounds. The participant will be provided with a carrying case to ensure the phone stays within five feet of their mouth. They will be asked to "wear" the phone for the duration of 3 weeks, and keep the phone within five feet of their mouth over nights - keeping it, i.e., on a bedside table. Hyfe is a research use only tool which does not provide clinical diagnosis. Cough collection within this study will not lead to specific medical interventions or differential clinical management. Hyfe records only short snippets (\<0.5 seconds). As such, the recordings will not be identifiable. Conversations or acoustic environments are not recorded. The informed consent form will explicitly describe exactly what is recorded.
EBC will be collected by asking the subject to breathe normally onto a handheld breath collection apparatus from Respire Diagnostics, Imperial College, that will cool the exhaled breath to allow for condensation of the exhaled air. The subject will breathe for 2 periods of 5 minutes each separated by a 3-4 min rest to allow the collection of up to 500 uL of liquid. The liquid will be stored for later analysis.
Continuous laryngoscopy testing is performed based on previous methodology. Continuous laryngoscopy testing is performed by placing a fibreoptic nasendoscope in the posterior nasopharynx and securing it using specialist headgear. A small quantity of lubricating jelly is used to ease passage of the scope. Video images of the laryngeal inlet are, thereafter, continuously recorded whilst a subject performs various manoeuvres including respiratory movements and cough. These movements will be observed and recorded before and following the various aspects of the challenge protocol and thus allow us to evaluate laryngeal movement abnormalities and for example position of the vocal folds. The size and change in size of the glottic aperture will be evaluated.
Sputum is induced by inhalation of an aerosol of sterile 3% saline solution and subsequently increasing to 4% and 5% during 3 periods of 5 minutes each. Particular care is taken to avoid contamination with saliva and post-nasal drip by instructing subjects to rinse orally with water and to blow their nose after each inhalation. Sputum samples are collected into sterile pots. Peak flow measurements are made after each inhalation. If there is a fall in peak flow of 20% or more or if symptoms occurred during the procedure, the induction is stopped. Sputum plugs are selected and one portion is used to perform differential cell counts. To perform differential cell counts, dithiothreitol is added to the sputum plug and mixed vigorously on a plate shaker to solubilize the sputum. Cytospins are then prepared, and differential cell counts obtained.
Spirometry (FEV1 and forced vital capacity, FVC) is measured using a dry wedge spirometer (Vitalograph, Buckinghamshire, UK).
Venous blood (30 cc) will be taken from a vein in the forearm. This test causes a transient discomfort as a needle is used to obtain the blood sample. The blood sample will be used for measuring various proteins and for getting white blood cells to obtain some types of stem cells.
Eligibility Criteria
You may qualify if:
- For Normal non-smoking subject:
- Healthy individuals, free of significant disease No history of asthma/rhinitis, No therapies, Baseline FEV1 ≥80% predicted with FEV1/FVC ratio \>70% Non-smoker for at least the past 12 months with a pack history of ≤5 pack-years
- For chronic cough participants:
- History of chronic cough of at least 8 weeks' duration and should have been followed in the Cough Clinic for at least 6 months.
- Undergone a protocol with a diagnostic pathway as recommended by the ERS guidelines for management of cough.
- Would have either an identifiable cause for their cough that have failed therapies targeted towards the identified cause or classed as having chronic idiopathic cough where no identifiable cause has been found.
- Give written informed consent prior to participation in the study including all of its procedures.
- Comply with the requirements and restrictions listed in the consent form. Male or female subject aged between 30 and 70 years old at screening. Able to complete the study and all measurements. Able to read, comprehend, and write at a sufficient level to complete study related materials.
You may not qualify if:
- Subjects will not be eligible if any of the following apply: -
- As a result of medical interview, physical examination or screening investigation the investigators consider the subject unfit either because of risk to the subject due to the study or the influence this may have on the study results.
- A history of recreational drug use or allergy which in the opinion of the investigators contra-indicates their participation.
- Female who is pregnant or lactating or up to 6 weeks post-partum or 6 weeks cessation of breast feeding at any point in the study.
- Any participants who are involved in current research or have recently been involved in any research prior to recruitment.
- Those, in the opinion of the investigator, who may prove non-compliant with study procedures.
- History of an upper or lower respiratory infection (including coryza) within 3 weeks of baseline assessments (assessments and entry could be deferred).
- Persons who might not adequately understand verbal explanations or written information given in English, or who have special communication needs.
- Subjects who are currently involved in other research.
- Subjects who are current smokers or ex-smokers with a greater than 10 pack-year history of smoking
- Subjects with significant presence of airflow obstruction with an FEV1 of \<70% of predicted for age and gender.
- Significant vocal cord disorder (VCD).
- Long term antibiotic treatment or receipt of a course within 4 weeks of bronchoscopy.
- Diagnosis of Allergic bronchopulmonary aspergillosis (ABPA), Churg-Strauss, rheumatoid arthritis, connective tissue disorders; Angiotensin-converting enzyme inhibitor and beta-blockers treatment.
- Morbid obesity (BMI\>35).
- +1 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Imperial College Londonlead
- Merck Sharp & Dohme LLCcollaborator
MeSH Terms
Conditions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Kian Fan Chung, MD
Imperial College London
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- DOUBLE
- Who Masked
- PARTICIPANT, INVESTIGATOR
- Masking Details
- Participant and Investigator will be blinded as to whether saline or ATP is being given.
- Purpose
- DIAGNOSTIC
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
January 12, 2023
First Posted
February 6, 2023
Study Start
February 28, 2023
Primary Completion
March 28, 2024
Study Completion
August 31, 2024
Last Updated
February 6, 2023
Record last verified: 2023-01