ATP and Capsaicin Cough Provocation Test in Chronic Cough and Bronchiectasis

• ClinicalTrials.gov Identifier: NCT03638063
• Recruitment Status: Unknown
• First Posted: August 20, 2018
• Last Update Posted: February 11, 2020
• Sponsor: Guangzhou Institute of Respiratory Disease
• Information provided by (Responsible Party): Weijie Guan, Guangzhou Institute of Respiratory Disease

Study Description

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.

Condition or disease	Intervention/treatment
Chronic Cough; Bronchiectasis	Diagnostic Test: Adenosine Triphosphate; Diagnostic Test: capsaicin

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.

Study Design

• Study Type: Observational
• Estimated Enrollment: 200 participants
• Observational Model: Case-Control
• Time Perspective: Cross-Sectional
• 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
• Actual Study Start Date: October 29, 2018
• Estimated Primary Completion Date: July 2020
• Estimated Study Completion Date: July 2020

Groups and Cohorts

Group/Cohort	Intervention/treatment
Chronic cough; patients with chronic cough who remain clinically stable	Diagnostic Test: Adenosine Triphosphate; Adenosine Triphosphate aerosol; Diagnostic Test: capsaicin; capsaicin aerosol
Bx; bronchiectasis patients who remain clinically stable	Diagnostic Test: Adenosine Triphosphate; Adenosine Triphosphate aerosol; Diagnostic Test: capsaicin; capsaicin aerosol
Control; healthy controls	Diagnostic Test: Adenosine Triphosphate; Adenosine Triphosphate aerosol; Diagnostic Test: capsaicin; capsaicin aerosol

Outcome Measures

Primary Outcome Measures :

1. C5 (Provocant concentration eliciting at least 5 coughs) [ Time Frame: 18 months ]
   Provocant concentration eliciting at least 5 coughs

Secondary Outcome Measures :

1. ED50 (half maximal effective Dose) [ Time Frame: 18 months ]
   50% effective dose of provocant
2. Emax (effective concentration of provocant eliciting maximal cough count) [ Time Frame: 18 months ]
   effective concentration of provocant eliciting maximal cough count
3. potency ratio [ Time Frame: 18 months ]
   ATP/capsaicin potency ratio
4. Difference in cough VAS score (a 10-point likert scale for assessing the global severity of cough, no subscale was applied) [ Time Frame: 18 months ]
   The difference between pre- and post-challenge cough VAS scores
5. The incidence of adverse events (i.e. dry throat , pharyngeal itching) [ Time Frame: 18 months ]
   adverse events such as dry throat , pharyngeal itching, wheeze or dyspnea according to the subject's reporting to record the rate of the incidence and the severity (the aboved-mentioned VAS score would be applied)
6. Cough dose ratio (CDR) [ Time Frame: 18 months ]
   the ratio of cough count and dose/concentration

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 60 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes
• Sampling Method: Non-Probability Sample

Study Population

patients with chronic cough (including bronchiectasis) who remained clinically stable for at least 4 weeks

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

Contacts and Locations

Contacts

Contact: Wei-jie Guan, MD; +86-13826042052; battery203@163.com

Contact: Jing jing Yuan, Msc; +86-13502414649; jacyyjj@163.com

Locations

China, Guangdong

First Affiliated Hospital of Guangzhou Medical University; Recruiting

Guangzhou, Guangdong, China

Contact: Wei-jie Guan battery203@163.com

Contact: Ke-fang Lai klai@163.com

Sponsors and Collaborators

Guangzhou Institute of Respiratory Disease

Investigators

• Study Chair: Ke-fang Lai, MD; Guangzhou Institute of Respiratory Health Locations: China, Guangdong First Affiliated Hospital of Guangzhou Medical

More Information

Publications:

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). pii: 1601452. doi: 10.1183/13993003.01452-2016. Print 2017 Feb.

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.

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. Epub 2006 Apr 6.

Fuller RW. Cough provocation tests: their clinical value. Pulm Pharmacol Ther. 2002;15(3):273-6. Review.

• Responsible Party: Weijie Guan, Associated professor; principal investigator (respiratory medicine), Guangzhou Institute of Respiratory Disease
• ClinicalTrials.gov Identifier: NCT03638063
• Other Study ID Numbers: GuangzhouIRD01
• First Posted: August 20, 2018
• Last Update Posted: February 11, 2020
• Last Verified: February 2020

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

Keywords provided by Weijie Guan, Guangzhou Institute of Respiratory Disease:

Adenosine triphosphate; Capsaicin; cough provocation test

Additional relevant MeSH terms:

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