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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT03722849




Registration number
NCT03722849
Ethics application status
Date submitted
24/10/2018
Date registered
29/10/2018
Date last updated
7/10/2019

Titles & IDs
Public title
Functional Magnetic Resonance Imaging of ATP Cough in Chronic Cough Patients
Scientific title
A Functional Magnetic Resonance Imaging Study to Investigate ATP-sensitive Cough Neural Pathways in Patients With Chronic Cough Hypersensitivity
Secondary ID [1] 0 0
Study 58136
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Cough 0 0
Condition category
Condition code
Respiratory 0 0 0 0
Other respiratory disorders / diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Adenosine Triphosphate
Treatment: Drugs - Capsaicin
Other interventions - Functional Brain Imaging

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.

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.


Treatment: Drugs: Adenosine Triphosphate
Participants will inhale escalating concentrations of Adenosine Triphosphate (ATP) to induce cough and the urge-to-cough

Treatment: Drugs: Capsaicin
Participants will inhale escalating concentrations of capsaicin to induce cough and the urge-to-cough

Other interventions: Functional Brain Imaging
Participants will have scans of their brain activity using 3 Tesla (3T) brainstem restricted functional brain imaging (fMRI)

Intervention code [1] 0 0
Treatment: Drugs
Intervention code [2] 0 0
Other interventions
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Brainstem neural activations - 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.
Timepoint [1] 0 0
18 months
Secondary outcome [1] 0 0
Behavioral responses - 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).
Timepoint [1] 0 0
18 months

Eligibility
Key inclusion criteria
- Patients with physician diagnosed chronic refractory cough (cough lasting >8 weeks).

- > 18 years of age

- Must be cognitively impaired
Minimum age
18 Years
Maximum age
No limit
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key 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).

Study design
Purpose of the study
Basic Science
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
The University of Melbourne - Parkville
Recruitment postcode(s) [1] 0 0
3010 - Parkville

Funding & Sponsors
Primary sponsor type
Other
Name
Stuart Mazzone
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
Imperial College London
Address [1] 0 0
Country [1] 0 0
Other collaborator category [2] 0 0
Other
Name [2] 0 0
Queen's University, Belfast
Address [2] 0 0
Country [2] 0 0
Other collaborator category [3] 0 0
Other
Name [3] 0 0
Monash University
Address [3] 0 0
Country [3] 0 0

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/show/NCT03722849
Trial related presentations / publications
Chung KF, Pavord ID. Prevalence, pathogenesis, and causes of chronic cough. Lancet. 2008 Apr 19;371(9621):1364-74. doi: 10.1016/S0140-6736(08)60595-4. Review.
Morice AH, Jakes AD, Faruqi S, Birring SS, McGarvey L, Canning B, Smith JA, Parker SM, Chung KF, Lai K, Pavord ID, van den Berg J, Song WJ, Millqvist E, Farrell MJ, Mazzone SB, Dicpinigaitis P; Chronic Cough Registry. A worldwide survey of chronic cough: a manifestation of enhanced somatosensory response. Eur Respir J. 2014 Nov;44(5):1149-55. doi: 10.1183/09031936.00217813. Epub 2014 Sep 3.
Chung KF, McGarvey L, Mazzone SB. Chronic cough as a neuropathic disorder. Lancet Respir Med. 2013 Jul;1(5):414-22. doi: 10.1016/S2213-2600(13)70043-2. Epub 2013 May 3. Review.
Mazzone SB, McLennan L, McGovern AE, Egan GF, Farrell MJ. Representation of capsaicin-evoked urge-to-cough in the human brain using functional magnetic resonance imaging. Am J Respir Crit Care Med. 2007 Aug 15;176(4):327-32. Epub 2007 Jun 15.
Ando A, Smallwood D, McMahon M, Irving L, Mazzone SB, Farrell MJ. Neural correlates of cough hypersensitivity in humans: evidence for central sensitisation and dysfunctional inhibitory control. Thorax. 2016 Apr;71(4):323-9. doi: 10.1136/thoraxjnl-2015-207425. Epub 2016 Feb 9.
Abdulqawi R, Dockry R, Holt K, Layton G, McCarthy BG, Ford AP, Smith JA. P2X3 receptor antagonist (AF-219) in refractory chronic cough: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 2015 Mar 28;385(9974):1198-205. doi: 10.1016/S0140-6736(14)61255-1. Epub 2014 Nov 25.
Public notes

Contacts
Principal investigator
Name 0 0
Stuart Mazzone, PhD
Address 0 0
University of Melbourne
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Stuart B Mazzone, PhD
Address 0 0
Country 0 0
Phone 0 0
+61383446457
Fax 0 0
Email 0 0
stuart.mazzone@unimelb.edu.au
Contact person for scientific queries

Summary results
For IPD and results data, please see https://clinicaltrials.gov/show/NCT03722849