Chronic CoughNCT06286163
Neuroinflammatory Interactions of ATP and P2X3 Receptor in the Airways of Chronic Cough Patients
An observational study of Chronic Cough, run by Imperial College London at 2 sites in United Kingdom.
Trial summary
This study is being done in order to understand what causes people to have a chronic cough, which is defined as a cough lasting for more than 8 weeks. The research team wish to find out whether there is any inflammation in the lungs of patients with chronic cough. Read more about this study
- Who is it for?
- Ages 30 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Chronic Cough
- How many people
- 18 participants
- Where
- 2 sitesUnited Kingdom
- Study dates
- 1 Oct 2023to 31 Dec 2025
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients who suffer from chronic cough and healthy volunteers
Who may be able to join
- 1. 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
- 2. 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.
- 3. General Inclusion Criteria: 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.
Who cannot join
- -
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United Kingdom2 sites, 2 recruiting
- Recruiting
Royal Brompton & Harefield NHS Trust,
London, SW3 6HP
Sally Meah, SRN, 0207 3518051, Sally.Meah@imperial.ac.uk
Pankaj K Bhavsar, 02075947961, p.bhavsar@imperial.ac.uk
- Recruiting
Royal Brompton Hospital
London, SW3 6HP
Kian Fan Chung, MD, 44205947959, f.chung@imperial.ac.uk
Sally Meah, SRN, 02073518051, Sally.Meah@imperial.ac.uk
About this study
Official title: Neuroinflammatory Interactions of ATP and P2X3 Receptor in the Airways of Chronic Cough Patients: an Exploratory Study
This study is being done in order to understand what causes people to have a chronic cough, which is defined as a cough lasting for more than 8 weeks. The research team wish to find out whether there is any inflammation in the lungs of patients with chronic cough. The research team will also determine whether a suspected chemical produced in the body, called adenosine triphosphate (ATP) can be responsible for causing the chronic cough. In order to be able to find out what is abnormal in those who have a chronic cough, The research team will need to compare their results with those that do not have a chronic cough.
In this study, the research team will examine 10 participants who suffer from chronic cough and 8 individuals who do not have a chronic cough and are healthy.
Read the detailed description
Background to problem Chronic cough is a very common clinical problem that is experienced by a large number of people and is a condition that can last for many years. It remains a difficult problem to treat by doctors because there is at present very poor understanding of what causes this condition of chronic cough. Consequently, the research team do not have much efficacious treatments for this common condition. Often, a cause for the cough can be identified by the doctor and treatment of the cause can help reduce or remove the cough. But in many instances, the cough may not be helped. In many cases also, the cause of the cough is not identified. These types of cough can be referred as being 'refractory' or 'idiopathic' or 'unexplained'.
Recently, the notion that chronic cough results from a state of hypersensitivity has been put forward to explain this condition. This has been put forward because those suffering from chronic cough often report that changes in ambient temperature, laughing, talking on the phone for more than a few minutes, aerosol sprays, or smoky atmospheres characteristically trigger bouts of coughing, indicating this state of hypersensitivity as a key common characteristic in this condition. Furthermore, this state of Cough Hypersensitivity Syndrome (CHS) could be caused by damage to the nerves (in the lungs and in the brain) by factors including viral infection, chemicals and inflammation. The nervous system controlling the sensitivity of the cough is necessarily complex and likely involves various molecules such as receptors and proteins that increase the sensitivity to cough.
Recently, a blocker of a receptor of a substance called Adenosine triphosphate (ATP), receptor P2X3, called AF-219 of Gefapixant has been shown to be extremely effective in suppressing the chronic cough of patients with an idiopathic cough, with a reduction in the number of coughs by 75% when compared to inactive drug 11. This is a very significant result because this study would suggest that this ATP receptor, P2X3, may play an important part in cough hypersensitivity syndrome. ATP is produced by cells and is the source of energy for cells needed for cellular functions such as movement of the cell and division of the cell.
Indeed, the academic community knows very little about the role of ATP and its receptor, P2X3, in chronic cough. First, it is possible that ATP may be released in greater amounts in chronic cough from activated or stressed cells in the airways, including nerves. ATP can cause inflammation and can be involved in the movement of inflammatory cells, production of oxygen free radicals by neutrophils and production of cytokines by inflammatory cells. ATP may induce a neuroimmune inflammatory response that could sensitise the peripheral nerves to cause this hypersensitivity. Through the PX3R, ATP can cause long-lasting allodynia through sensitisation of these receptors. Patients with chronic cough cough more to inhaled ATP compared to healthy subjectsparticipants.
Therefore, The research team want to show that:
- ATP is released by cough stimuli and stimulates P2X3 receptors in the upper and lower airways
- The increased sensory state of the peripheral sensory nerves leads to activation of P2X3 4 Together, these form the basis of cough hypersensitivity syndrome
- Conditions
- Chronic Cough
- Medical subject headings
- Chronic Cough
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Chronic Cough | 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. | |
| Healthy | 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 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Presence of ATP in airways of idiopathic chronic cough patients and the localisation of P2X2/3 receptors in the airways
Measure ATP concentrations in exhaled breath condensate and use immunohistochemistry to identify P2X2/3 receptors in lung endobronchial biopsies.
Measured: 18 months
Cough sensitivity and laryngeal sensitivity to exogenous ATP
Count the number of cough in response to capsaicin pre and post ATP exposure
Measured: 18 months
Examine the effects of exogenous ATP on the inflammatory response in the upper and lower airways.
Count the number of immune cells in sputum and BALF pre and post ATP by microscopy
Measured: 18 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Feb 2024
- Study start1 Oct 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic CoughStudies of the same condition, open and under way.
- More trials run by Imperial College LondonThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 18 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Imperial College London
- Sponsor type
- University, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Responsible party
- Sponsor
- Investigators
- Kian Fan Chung, MD, Principal investigator, Imperial College London
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06286163
- Sponsor's protocol ID
- PA4099
- Status last verified
- Feb 2025
- First submitted
- 22 Feb 2024
- Last updated
- 7 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neuroinflammatory Interactions of ATP and P2X3 Receptor in the Airways of Chronic Cough Patients: an Exploratory Study
- ClinicalTrials.gov ID
- NCT06286163
- Acronym / sponsor ID
- PA4099
- Conditions
- Chronic Cough
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 18 participants (estimated)
- Lead sponsor
- Imperial College LondonUniversity, hospital or other
- Collaborators
- Merck Sharp & Dohme LLC
- Study start
- 1 Oct 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2025 (estimated)
- First posted
- 29 Feb 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is being done in order to understand what causes people to have a chronic cough, which is defined as a cough lasting for more than 8 weeks. The research team wish to find out whether there is any inflammation in the lungs of patients with chronic cough. The research team will also determine whether a suspected chemical produced in the body, called adenosine triphosphate (ATP) can be responsible for causing the chronic cough. In order to be able to find out what is abnormal in those who have a chronic cough, The research team will need to compare their results with those that do not have a chronic cough.
In this study, the research team will examine 10 participants who suffer from chronic cough and 8 individuals who do not have a chronic cough and are healthy.
Detailed description
Background to problem Chronic cough is a very common clinical problem that is experienced by a large number of people and is a condition that can last for many years. It remains a difficult problem to treat by doctors because there is at present very poor understanding of what causes this condition of chronic cough. Consequently, the research team do not have much efficacious treatments for this common condition. Often, a cause for the cough can be identified by the doctor and treatment of the cause can help reduce or remove the cough. But in many instances, the cough may not be helped. In many cases also, the cause of the cough is not identified. These types of cough can be referred as being 'refractory' or 'idiopathic' or 'unexplained'.
Recently, the notion that chronic cough results from a state of hypersensitivity has been put forward to explain this condition. This has been put forward because those suffering from chronic cough often report that changes in ambient temperature, laughing, talking on the phone for more than a few minutes, aerosol sprays, or smoky atmospheres characteristically trigger bouts of coughing, indicating this state of hypersensitivity as a key common characteristic in this condition. Furthermore, this state of Cough Hypersensitivity Syndrome (CHS) could be caused by damage to the nerves (in the lungs and in the brain) by factors including viral infection, chemicals and inflammation. The nervous system controlling the sensitivity of the cough is necessarily complex and likely involves various molecules such as receptors and proteins that increase the sensitivity to cough.
Recently, a blocker of a receptor of a substance called Adenosine triphosphate (ATP), receptor P2X3, called AF-219 of Gefapixant has been shown to be extremely effective in suppressing the chronic cough of patients with an idiopathic cough, with a reduction in the number of coughs by 75% when compared to inactive drug 11. This is a very significant result because this study would suggest that this ATP receptor, P2X3, may play an important part in cough hypersensitivity syndrome. ATP is produced by cells and is the source of energy for cells needed for cellular functions such as movement of the cell and division of the cell.
Indeed, the academic community knows very little about the role of ATP and its receptor, P2X3, in chronic cough. First, it is possible that ATP may be released in greater amounts in chronic cough from activated or stressed cells in the airways, including nerves. ATP can cause inflammation and can be involved in the movement of inflammatory cells, production of oxygen free radicals by neutrophils and production of cytokines by inflammatory cells. ATP may induce a neuroimmune inflammatory response that could sensitise the peripheral nerves to cause this hypersensitivity. Through the PX3R, ATP can cause long-lasting allodynia through sensitisation of these receptors. Patients with chronic cough cough more to inhaled ATP compared to healthy subjectsparticipants.
Therefore, The research team want to show that:
- ATP is released by cough stimuli and stimulates P2X3 receptors in the upper and lower airways
- The increased sensory state of the peripheral sensory nerves leads to activation of P2X3 4 Together, these form the basis of cough hypersensitivity syndrome
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Chronic Cough | – | –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. |
| Healthy | – | –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 |
Who may qualify
- Ages
- 30 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients who suffer from chronic cough and healthy volunteers
Key inclusion criteria (6 listed)
- 1. 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
- 2. 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.
- 3. General Inclusion Criteria: 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.
Key exclusion criteria (1 listed)
- -
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Presence of ATP in airways of idiopathic chronic cough patients and the localisation of P2X2/3 receptors in the airways
Time frame: 18 months
Measure ATP concentrations in exhaled breath condensate and use immunohistochemistry to identify P2X2/3 receptors in lung endobronchial biopsies.
Cough sensitivity and laryngeal sensitivity to exogenous ATP
Time frame: 18 months
Count the number of cough in response to capsaicin pre and post ATP exposure
Examine the effects of exogenous ATP on the inflammatory response in the upper and lower airways.
Time frame: 18 months
Count the number of immune cells in sputum and BALF pre and post ATP by microscopy
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2025.
- Individual participant dataSharing planned: No
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Not yet recruitingPhase 4
A 2x2 Factorial, Randomized, Open-label Trial to Evaluate Neuromodulators and Cough Control Therapy in Patients With Refractory or Unexplained Chronic Cough
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Kian Fan Chung, MD principal investigator
Imperial College London
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Chronic Cough, run by Imperial College London at 2 sites in United Kingdom.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 7 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United Kingdom. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Kian Fan Chung, MD (442075947959, f.chung@imperial.ac.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Presence of ATP in airways of idiopathic chronic cough patients and the localisation of P2X2/3 receptors in the airways (time frame: 18 months). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Feb 2025.