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

NCT06600646 | Recruiting FDA Device

• 1 other identifier: Hireb:17668
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Chronic Cough (CC)

Keywords

chronic cough; ATP; airway nerves

Outcome Measures

Primary Outcomes (1)

• Difference in expressed genes

  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 Outcomes (4)

• Difference Immune Cells and Cytokines

  12 months

• Gene Expression

  At baseline

• Difference in Nerve Morphology

  baseline

• Difference in ATP release

  5,15,30 minutes

Study Arms (2)

Refractory or Unexplained Chronic Cough

Diagnostic Test: Bronchoscopy

Healthy Controls

Diagnostic Test: Bronchoscopy

Interventions

Bronchoscopy DIAGNOSTIC_TEST

Bronchoscopy will be performed in patients with refractory or unexplained chronic cough and healthy controls.

Healthy Controls; Refractory or Unexplained Chronic Cough

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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

You may qualify if:

• 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.
• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• McMaster University: lead

Study Sites (1)

Imran Satia

Hamilton, Ontario, L8S 4L8, Canada

RECRUITING

Biospecimen

Retention: SAMPLES WITH DNA

Bronchial Biopsies for RNA sequencing.

MeSH Terms

Conditions

Chronic Cough

Interventions

Bronchoscopy

Condition Hierarchy (Ancestors)

Cough; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diagnostic Techniques, Respiratory System; Diagnostic Techniques and Procedures; Diagnosis; Endoscopy; Diagnostic Techniques, Surgical; Minimally Invasive Surgical Procedures; Surgical Procedures, Operative; Pulmonary Surgical Procedures; Thoracic Surgical Procedures

Study Officials

• Imran Satia, MB BChir (cantab) MRCP PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Imran Satia, MB BChir (cantab) MRCP PhD

CONTACT

905-521-2100; satiai@mcmaster.ca

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2024
• First Posted: September 19, 2024
• Study Start: November 22, 2024
• Primary Completion: October 1, 2025
• Study Completion: December 31, 2025
• Last Updated: May 8, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)