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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 : Not yet recruiting
First Posted : October 29, 2018
Last Update Posted : October 29, 2018
Sponsor:
Collaborators:
Imperial College London
Queen's University, Belfast
Monash University
Information provided by (Responsible Party):
Stuart Mazzone, University of Melbourne

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.

Condition or disease Intervention/treatment Phase
Cough Drug: Adenosine Triphosphate Drug: Capsaicin Other: Functional Brain Imaging Not Applicable

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 50 participants
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
Official Title: A Functional Magnetic Resonance Imaging Study to Investigate ATP-sensitive Cough Neural Pathways in Patients With Chronic Cough Hypersensitivity
Estimated Study Start Date : January 1, 2019
Estimated Primary Completion Date : July 30, 2020
Estimated Study Completion Date : July 30, 2020

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.

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

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.

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




Primary Outcome Measures :
  1. 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.


Secondary Outcome Measures :
  1. 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).



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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).

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03722849


Contacts
Contact: Stuart B Mazzone, PhD +61383446457 stuart.mazzone@unimelb.edu.au
Contact: Alice E McGovern, PhD +61383443979 alice.mcgovern@unimelb.edu.au

Sponsors and Collaborators
Stuart Mazzone
Imperial College London
Queen's University, Belfast
Monash University
Investigators
Principal Investigator: Stuart Mazzone, PhD University of Melbourne

Publications:

Responsible Party: Stuart Mazzone, Associate Professor of Neuroscience, University of Melbourne
ClinicalTrials.gov Identifier: NCT03722849     History of Changes
Other Study ID Numbers: Study 58136
First Posted: October 29, 2018    Key Record Dates
Last Update Posted: October 29, 2018
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: IPD will not be shared

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Stuart Mazzone, University of Melbourne:
functional brain imaging
ATP
Capsaicin
Refractory cough

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Cough
Respiration Disorders
Respiratory Tract Diseases
Signs and Symptoms, Respiratory
Signs and Symptoms
Adenosine
Capsaicin
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Arrhythmia Agents
Vasodilator Agents
Purinergic P1 Receptor Agonists
Purinergic Agonists
Purinergic Agents
Neurotransmitter Agents
Antipruritics
Dermatologic Agents