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

May 5, 2025 updated by: McMaster University
Chronic cough is a common troublesome symptom which has a global prevalence of approximately 10%, but with wide variations across continents. Patients with refractory and unexplained chronic cough (RCC/UCC) often exhibit dysregulated vagal pathways, necessitating a neuronal biomarker for targeted treatment. ATP, involved in the ATP/P2X3 pathway, may serve as a potential biomarker due to its role in the cough reflex. The study aims to discover if ATP production by the airway epithelium is greater in RCC/UCC patients compared with healthy controls, if the epithelium is a source of ATP, whether gene and protein expression related to ATP production differs between these groups and whether ATP release is triggered by mechanical and chemical stimulation. Additionally, the study seeks to determine if biomarker gene expression signatures can differentiate RCC/UCC patients from healthy controls.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Observational

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
30

Contacts and Locations

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

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Imran Satia, MB BChir (cantab) MRCP PhD
  • Phone Number: 76645 905-521-2100
  • Email: satiai@mcmaster.ca

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8S 4L8

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

Healthy controls will be recruited through local advertising, existing study databases or participation in previous studies where they have given permission to be contacted. Participants with RCC/UCC will be recruited by the investigators from existing study databases, clinics at either of the following sites:

McMaster University Medical Centre, Department of Respiratory Medicine, 1200 Main St. West, Hamilton, Ontario, Canada, L8N 3Z5

Firestone Institute for Respiratory Health, St Joseph's Healthcare, 50 Charlton Ave E, Hamilton, ON L8N 4A6

Description

Inclusion Criteria for RCC/UCC:

  • Patients with a history of RCC/UCC.
  • Normal Chest X-ray in the last 5 years.
  • No Evidence of Airflow Obstruction (FEV1/FVC ratio above LLN)
  • Cough Severity VAS ≥ 40 mm at screening.

Inclusion Criteria for Healthy Controls:

  • No history of chronic cough, asthma, COPD, or clinical history of bronchiectasis or interstitial lung disease
  • No current smokers or those with >10 pack year history.
  • No evidence of airflow obstruction ( FEV1/FVC ratio above LLN).
  • Able to understand and give written informed consent.

Exclusion Criteria:

  • Participants who are currently established on treatment and their chronic cough is well controlled.
  • Unable to perform acceptable and reproducible spirometry.
  • Participants with a positive covid-19 test within 2 weeks of screening.
  • Current smoker or ex-smoker with ≥20 pack year smoking history and abstinence of ≤6 months
  • Symptoms of upper respiratory tract infection in the last 1 month which have not resolved
  • Lower respiratory tract infection or pneumonia in the last 1 month
  • Asthma exacerbation in the previous month requiring an increase or start of an inhaled corticosteroid (ICS) or oral corticosteroid (OCS)
  • Significant other primary pulmonary disorders in particular; pulmonary embolism, pulmonary hypertension, lung cancer, cystic fibrosis, significant radiologically proven emphysema, interstitial lung disease or bronchiectasis.
  • History of psychiatric illness, drug or alcohol abuse which may interfere in the participation of the trial.
  • Allergy or intolerance to sedation medication including fentanyl and midazolam, or a history of complications during procedural sedation
  • Severe coagulopathy, bleeding disorder, or medical need for anti- coagulation that would increase the risk of endobronchial biopsy as determined by the investigator

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

Cohorts and Interventions

Group / Cohort

Group / Cohort

A group or subgroup of participants in an observational study that is assessed for biomedical or health outcomes.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Healthy Controls
Diagnostic test: Bronchoscopy
Bronchoscopy will be performed in patients with refractory or unexplained chronic cough and healthy controls.
Refractory or Unexplained Chronic Cough
Diagnostic test: Bronchoscopy
Bronchoscopy will be performed in patients with refractory or unexplained chronic cough and healthy controls.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Difference in expressed genes
Time Frame: At baseline
Expression of genes involved in intracellular ATP production, transport, extracellular metabolism in the airway epithelium will be compared in both RCC/UCC and healthy controls.
At baseline

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Difference Immune Cells and Cytokines
Time Frame: 12 months
Investigate differences in the levels of neuroinflammatory mediators and immune cells from the respiratory airways and distal alveoli.
12 months
Gene Expression
Time Frame: At baseline
To compare the differences in RCC/UCC and healthy control in gene expression profiling in bronchial biopsies (sub-epithelial dominant).
At baseline
Difference in Nerve Morphology
Time Frame: baseline
Investigate differences in nerve length, nerve branch points, nerves expressive P2X3 receptors on airway sensory nerves expressing P2X3 receptor in RCC/UCC compared with healthy controls.
baseline
Difference in ATP release
Time Frame: 5,15,30 minutes
ATP release from the cultured bronchial epithelial cells (BEC) taken from RCC/UCC and healthy controls after exposure to dynamic mechanical stretch and environmental exposures (cigarette smoke and NO2).
5,15,30 minutes

Collaborators and Investigators

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

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
McMaster University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Imran Satia, MB BChir (cantab) MRCP PhD, McMaster University

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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 22, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2025

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2025

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 12, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 16, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 19, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 8, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 5, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • Hireb:17668

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD Plan Description

This is an single visit of 15 patients with RCC/UCC compared with 15 Healthy Controls undergoing bronchoscopy at single centre in Hamilton, Ontario, Canada. Due to the small sample size individual level details will not be shared to protect confidentiality.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

Yes

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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