Neuroinflammatory Interactions of ATP and P2X3 Receptor in the Airways of Chronic Cough Patients

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

RECRUITING

Total Enrollment

18 participants

Study Classification

OBSERVATIONAL

Study Start Date

2023-10-01

Study Completion Date

2025-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

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.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

Investigating the Role of ATP Production by Airway Epithelium in Patients With Refractory and Unexplained Chronic Cough (RCC/UCC).

NCT06600646

Chronic Cough (CC)

RECRUITING

Chronic COUGH Management in Interstitial Lung DisEase

NCT06782893

Interstitial Lung Disease Chronic Cough

NOT_YET_RECRUITING NA

Prospective Study on the Evaluation, Patient Reported Outcomes and Effectiveness of Treatment for Chronic Cough

NCT04758351

Chronic Cough

COMPLETED

An Observational Study Using Novel Questionnaire to Characterize Cough Phenotypes in Patients With Chronic Cough

NCT06376448

Chronic Cough

RECRUITING

Exacerbations in Severe Asthma Patients: Mechanisms and Biomarkers

NCT02660853

Asthma

COMPLETED NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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:

1. ATP is released by cough stimuli and stimulates P2X3 receptors in the upper and lower airways
2. 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

See the medical conditions and disease areas that this research is targeting or investigating.

Chronic Cough

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

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.

No interventions assigned to this group

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

No interventions assigned to this group

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

\- 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.

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.