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Functional Magnetic Resonance Imaging of ATP Cough in Chronic Cough Patients

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ClinicalTrials.gov Identifier: NCT03722849
Recruitment Status : Recruiting
First Posted : October 29, 2018
Last Update Posted : October 7, 2019
Sponsor:
Collaborators:
Imperial College London
Queen's University, Belfast
Monash University
Information provided by (Responsible Party):
Stuart Mazzone, University of Melbourne

Tracking Information
First Submitted Date  ICMJE October 24, 2018
First Posted Date  ICMJE October 29, 2018
Last Update Posted Date October 7, 2019
Actual Study Start Date  ICMJE March 1, 2019
Estimated Primary Completion Date July 30, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 25, 2018)
Brainstem neural activations [ Time Frame: 18 months ]
fMRI will be used to determine the location and magnitude of neural responses in the brain during ATP and capsaicin inhalation. fMRI non-invasively measures Blood Oxygen Level Dependent (BOLD) signals in the brain which can be used to identify regions of the brain that increase activity associated with the inhaled stimuli. Comparisons between regional BOLD responses evoked by ATP and capsaicin (compared to saline) will allow the different neural networks involved in cough generation to be explored in healthy and chronic cough participants.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 25, 2018)
Behavioral responses [ Time Frame: 18 months ]
Participant responses (cough and the urge-to-cough) evoked by ATP and capsaicin will be measured by counting audible coughs and by asking participants to rate their perception of urge-to-cough using visual analogue scales (VAS).
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Functional Magnetic Resonance Imaging of ATP Cough in Chronic Cough Patients
Official Title  ICMJE A Functional Magnetic Resonance Imaging Study to Investigate ATP-sensitive Cough Neural Pathways in Patients With Chronic Cough Hypersensitivity
Brief Summary Persistent cough is a distressing symptom for people with respiratory disorders. Patients also often experience an ongoing urge-to-cough that prompts coughing, and which fails to resolve the sensation. Understanding how the brain controls cough and the urge-to-cough could lead to new cough suppressing therapies. The overall objective of this project is to use functional brain imaging (fMRI) to identify brain regions that are involved in the exaggerated urge-to-cough in humans with chronic cough. Our focus will be on the brainstem where information from the airways first arrives in the central nervous system.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Intervention Model Description:
The experiment will consist of two sessions. The first session will involve questionnaires, followed by measures of sensitivity and behavioural responses to tussive (cough evoking) stimulation. The second session will involve functional brain imaging measures of responses to tussive stimulation.
Masking: None (Open Label)
Primary Purpose: Basic Science
Condition  ICMJE Cough
Intervention  ICMJE
  • Drug: Adenosine Triphosphate
    Participants will inhale escalating concentrations of Adenosine Triphosphate (ATP) to induce cough and the urge-to-cough
    Other Name: ATP
  • Drug: Capsaicin
    Participants will inhale escalating concentrations of capsaicin to induce cough and the urge-to-cough
  • Other: Functional Brain Imaging
    Participants will have scans of their brain activity using 3 Tesla (3T) brainstem restricted functional brain imaging (fMRI)
    Other Name: fMRI
Study Arms  ICMJE
  • Experimental: Chronic cough participant

    Twenty-five (25) Idiopathic chronic cough patients, defined as refractory to disease modifying therapies (eg anti-asthma medications), will be recruited.

    Participants will attend two sessions. In the first they will inhale in a single breath a nebulized solutions of increasing doses of Adenosine Triphosphate (ATP; 0.2-300 microM) and capsaicin (0.5-125 microM) to determine their individual cough and urge-to-cough thresholds. In the second session, participants will undergo functional brain imaging (fMRI) for 1 hour while inhaling over 24 seconds randomly administered nebulized solutions of saline, or threshold doses of ATP or capsaicin.

    Interventions:
    • Drug: Adenosine Triphosphate
    • Drug: Capsaicin
    • Other: Functional Brain Imaging
  • Experimental: Healthy control participant

    Twenty-five (25) appropriately age and sex matched healthy non-smoking individuals will be recruited as the comparison group.

    Participants will attend two sessions. In the first they will inhale in a single breath a nebulized solutions of increasing doses of ATP (0.2-300 microM) and capsaicin (0.5-125 microM) to determine their individual cough and urge-to-cough thresholds. In the second session, participants will undergo fMRI for 1 hour while inhaling over 24 seconds randomly administered nebulized solutions of saline, or threshold doses of ATP or capsaicin.

    Interventions:
    • Drug: Adenosine Triphosphate
    • Drug: Capsaicin
    • Other: Functional Brain Imaging
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 25, 2018)
50
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE July 30, 2020
Estimated Primary Completion Date July 30, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with physician diagnosed chronic refractory cough (cough lasting >8 weeks).
  • > 18 years of age
  • Must be cognitively impaired

Exclusion Criteria:

  • People with contraindications to MRI scanning (i.e. metal implants, claustrophobia).
  • History of uncontrolled asthma or chronic respiratory disease (other than refractory cough).
  • Evidence of an allergic reaction to capsaicin (chilli).
  • Pregnant women.
  • Smoking, current or recent history (last 6 months).
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE
Contact: Stuart B Mazzone, PhD +61383446457 stuart.mazzone@unimelb.edu.au
Contact: Alice E McGovern, PhD +61383443979 alice.mcgovern@unimelb.edu.au
Listed Location Countries  ICMJE Australia
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03722849
Other Study ID Numbers  ICMJE Study 58136
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Plan Description: IPD will not be shared
Responsible Party Stuart Mazzone, University of Melbourne
Study Sponsor  ICMJE Stuart Mazzone
Collaborators  ICMJE
  • Imperial College London
  • Queen's University, Belfast
  • Monash University
Investigators  ICMJE
Principal Investigator: Stuart Mazzone, PhD University of Melbourne
PRS Account University of Melbourne
Verification Date October 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP