ToAST:Investigating the Effect of Bronchial Thermoplasty on Cough in Patients With Severe Asthma (ToAST)

ToAST: Investigating the Effect of Bronchial Thermoplasty on Cough in Patients With Severe Asthma

ToAST study is a pilot study aiming to establish the safety profile of using inhaled capsaicin challenge in patients with severe asthma. The investigators will also explore the differences in cough symptoms and threshold in patients with and without bronchial thermoplasty.

Study Overview

• Status: Unknown
• Conditions: Asthma Chronic, Cough
• Intervention / Treatment: Other: Inhaled capsaicin cough challenge

Detailed Description

ToAST is designed as a two-visit observational study. During visit 1, written consent and measurements of baseline asthma characteristics were completed; history and examination, questionnaires (Asthma Control Questionnaires and Leicester Cough Questionnaire, and basic lung physiological assessment were performed.

At the end of visit 1, a cough monitor was attached to the subject to monitor cough frequency for the next 24 hours and this was returned at visit 2.

Visit 2 followed within two weeks after visit 1, during which a full dose capsaicin cough challenge was performed. Emergency contact details were given towards end of visit 2 should any adverse events occur.

Telephone call within 48 hours, Day 3 and Day 7: The purpose of these phone calls was to ensure that the patient had not developed any adverse effects to the capsaicin challenge.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Manchester, United Kingdom, M23 9LT
    • Recruiting
    • University Hospital of South Manchester
    • Contact: Ran Wang, Dr; Phone Number: 7557761062; Email: ranwang1986@googlemail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged ≥18
• Person with an established diagnosis of severe asthma
• All patients should be on British Thoracic Society (BTS) steps 4 or 5
• Patients who have had bronchial thermoplasty (BT) should be at least 2 months after their treatment
• Historical evidence of one of the following:
• Airway reversibility to a short acting beta-2 agonist of ≥12%
• Bronchial hyper-responsiveness (PC20<8mg/ml)
• Fractional exhaled nitric oxide ≥50ppb
• Peak flow variability >8%
• Raised serum (≥0.45) or sputum eosinophilia (>3%)
• Variability in spirometry over 24 months of >20%

Exclusion Criteria:

• Unable to give informed consent
• FEV1<50% predicted or < 1 litre
• Known allergy or intolerance to capsaicin
• Symptoms of upper respiratory tract infection in the last 1 month which have not resolved.
• Lower respiratory tract infection or pneumonia in the last 6 weeks.
• Current smoker or ex-smoker with ≥10 pack year smoking history, abstinence of ≤6 months
• Asthma exacerbation in the previous month requiring an increase or starting of an ICS or OCS
• Subject has changed asthma medication within the past 4 weeks prior to screening
• A previous asthma exacerbation requiring Intensive Care Unit (ICU) admission.
• Significant other pulmonary disorders as the major diagnosis, in particular: pulmonary embolism, pulmonary hypertension, interstitial lung disease, lung cancer, cystic fibrosis, emphysema or bronchiectasis.
• Evidence of vocal cord dysfunction
• Pregnancy or breast-feeding
• Use of ACE inhibitors
• Any centrally acting medication which in the view of the investigator could alter the sensitivity of the cough reflex*
• History of psychiatric illness, drug or alcohol abuse which may interfere in the participation of the trial.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Patients without BT	Other: Inhaled capsaicin cough challenge
Other: Post BT	Other: Inhaled capsaicin cough challenge

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of participants who has had significant fall in FEV1 (defined as >20%) within the challenge period	By measuring spirometry immediately before and after challenge	Through study completion, an average of 6 months
Number of participants who require bronchodilator treatment during capsaicin challenge period	Defined as rescue medications - 2 puffs of salbutamol inhaler via spacer	Through study completion, an average of 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in %FEV1 predicted during capsaicin challenge period in all subjects	By measuring spirometry immediately before and after challenge	Through study completion, an average of 6 months
The tolerability of inhaled capsaicin in severe asthma	By exploring the pattern of termination of challenge in severe asthma	Through study completion, an average of 6 months
The number of adverse events in all subjects during and after capsaicin evoked cough challenge	by follow up phone calls at 48 hours, 3 days and 7 days to assess AE and SAE	Through study completion, an average of 6 months
Degree of breathlessness during capsaicin challenge period assessed by using modified Borg scale (mBorg).	By calculating Borg immediately before and after challenge to assess level of breathlessness.	Through study completion, an average of 6 months
Degree of breathlessness during capsaicin challenge period assessed by using dysnoea Visual Analogue Score (dVAS).	By calculating dVAS immediately before and after challenge to assess level of breathlessness.	Through study completion, an average of 6 months
Differences in capsaicin dose response curves (Maximum cough response evoked by any concentration of capsaicin- Emax and Capsaicin dose inducing half-maximal response - ED50) between subjects who have had BT versus those have not	by comparing post-BT and no-BT patients	Through study completion, an average of 6 months
The differences in 24-hour cough frequency between patients who have had BT and those who have not.	by comparing post-BT and no-BT patients	Through study completion, an average of 6 months
The differences in Leicester cough questionnaire (LCQ) between patients who have had BT and those who have not.	by comparing post-BT and no-BT patients	Through study completion, an average of 6 months
The differences in asthma control questionnaire(ACQ) between patients who have had BT and those who have not.	by comparing post-BT and no-BT patients	Through study completion, an average of 6 months
The differences of the dose response curves in patients with severe asthma with existing data of capsaicin challenge in patients with healthy and mild/moderate asthma (in Emax and ED50).	By comparing with existing data.	Through study completion, an average of 6 months

Collaborators and Investigators

• Sponsor: National Health Service, United Kingdom

Study record dates

Study Major Dates

• Study Start (Actual): August 6, 2016
• Primary Completion (Anticipated): February 1, 2018
• Study Completion (Anticipated): February 1, 2018

Study Registration Dates

• First Submitted: August 22, 2017
• First Submitted That Met QC Criteria: September 11, 2017
• First Posted (Actual): September 13, 2017

Study Record Updates

• Last Update Posted (Actual): September 13, 2017
• Last Update Submitted That Met QC Criteria: September 11, 2017
• Last Verified: September 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Respiration Disorders; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Signs and Symptoms, Respiratory; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Cough; Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Dermatologic Agents; Antipruritics; Capsaicin
• Other Study ID Numbers: NHSUK

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No