Clinical trial NCT03638063: ATP and Capsaicin Cough Provocation Test in Chronic Cough and Bronchiectasis
Official title: Adenosine Triphosphate and Capsaicin Cough Provocation Test for Identifing Patients With Chronic Cough Who Have Differential Responses to Purinergic Receptor Antagonists: a Randomized, Cross-over, Single-blind Trial
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Chronic Cough
Bronchiectasis
Keywords: Adenosine triphosphate
Capsaicin
cough provocation test
Lead sponsor: Guangzhou Institute of Respiratory Disease
Sponsor class: OTHER
First posted: 2018-08-20
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Observational model: CASE_CONTROL
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: patients with chronic cough (including bronchiectasis) who remained clinically stable for at least 4 weeks

Brief summary: This is a randomized, cross-over, single-blind trial. Eligible patients will be randomly assigned to undergo either capsaicin or adenosine triphosphate (ATP) cough provocation test, followed by a washout period of 2 to 14 days. Participants will be crossed-over to undergo another cough provocation test. Patient would be under observation in the out-patient clinics for \~2 hours following the cough provocation tests in case of severe adverse events.

Detailed description: This is a randomized, cross-over, single-blind trial. After verification of the entry criteria, eligible patients will be, based on the randomization codes, randomly assigned to undergo either capsaicin or ATP cough provocation test (the participants will inhale capasaicin or ATP incremental concentration to induce cough, meanwhile the number of coughs and adverse events will be recorded in each concentration during the first 30 seconds), followed by a washout period of 2 to 14 days (no major changes in the use of concomitant medications are allowed,especially the medcines which are not allowed before test ). Participants will be crossed-over to undergo another cough provocation test. Patient would be under observation in the out-patient clinics for \~2 hours following the cough provocation tests in case of severe adverse events. Twenty four hours after each test, a follow-up telephone visit will be scheduled for all patients to record any response which may be related to the test.

Eligibility criteria: Inclusion Criteria:

* Out-patients of either gender, ex- or never-smokers, aged between 18 and 60 years
* Cough symptoms lasting for more than 8 weeks
* Remaining free of acute upper respiratory tract infection for at least 4 weeks
* Agreed to participate in the trial and signed informed consent.

Exclusion Criteria:

* Patients with serious systemic diseases (such as malignant tumors), bullae, severe uncontrolled asthma, and a history of major hemoptysis
* Systemic antibiotic use (except for maintenance low-dose macrolides) within 4 weeks
* Pregnancy or lactation
* Any known history of sensitivity to ATP or capsaicin
* Poor understanding of the test procedure
* Diagnosed with cough variant asthma or Eosinophilic bronchitis

Primary outcomes:
measure: C5 (Provocant concentration eliciting at least 5 coughs)
timeFrame: 18 months
Secondary outcomes:
measure: ED50 (half maximal effective Dose)
timeFrame: 18 months
measure: Emax (effective concentration of provocant eliciting maximal cough count)
timeFrame: 18 months
measure: potency ratio
timeFrame: 18 months
measure: Difference in cough VAS score (a 10-point likert scale for assessing the global severity of cough, no subscale was applied)
timeFrame: 18 months
measure: The incidence of adverse events (i.e. dry throat , pharyngeal itching)
timeFrame: 18 months
measure: Cough dose ratio (CDR)
timeFrame: 18 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: First Affiliated Hospital of Guangzhou Medical University
state: Guangdong
Study officials:
affiliation: Guangzhou Institute of Respiratory Health Locations: China, Guangdong First Affiliated Hospital of Guangzhou Medical
name: Ke-fang Lai, MD
role: STUDY_CHAIR
References:
citation: Fowles HE, Rowland T, Wright C, Morice A. Tussive challenge with ATP and AMP: does it reveal cough hypersensitivity? Eur Respir J. 2017 Feb 8;49(2):1601452. doi: 10.1183/13993003.01452-2016. Print 2017 Feb.
citation: Guan WJ, Gao YH, Xu G, Lin ZY, Tang Y, Li HM, Lin ZM, Zheng JP, Chen RC, Zhong NS. Capsaicin cough sensitivity and the association with clinical parameters in bronchiectasis. PLoS One. 2014 Nov 19;9(11):e113057. doi: 10.1371/journal.pone.0113057. eCollection 2014.
citation: Torrego A, Haque RA, Nguyen LT, Hew M, Carr DH, Wilson R, Chung KF. Capsaicin cough sensitivity in bronchiectasis. Thorax. 2006 Aug;61(8):706-9. doi: 10.1136/thx.2005.049767. Epub 2006 Apr 6.
citation: Fuller RW. Cough provocation tests: their clinical value. Pulm Pharmacol Ther. 2002;15(3):273-6. doi: 10.1006/pupt.2002.0355.