<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03281941</url>
  </required_header>
  <id_info>
    <org_study_id>NHSUK</org_study_id>
    <nct_id>NCT03281941</nct_id>
  </id_info>
  <brief_title>ToAST:Investigating the Effect of Bronchial Thermoplasty on Cough in Patients With Severe Asthma</brief_title>
  <acronym>ToAST</acronym>
  <official_title>ToAST: Investigating the Effect of Bronchial Thermoplasty on Cough in Patients With Severe Asthma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Health Service, United Kingdom</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Health Service, United Kingdom</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      ToAST study is a pilot study aiming to establish the safety profile of using inhaled&#xD;
      capsaicin challenge in patients with severe asthma. The investigators will also explore the&#xD;
      differences in cough symptoms and threshold in patients with and without bronchial&#xD;
      thermoplasty.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      ToAST is designed as a two-visit observational study. During visit 1, written consent and&#xD;
      measurements of baseline asthma characteristics were completed; history and examination,&#xD;
      questionnaires (Asthma Control Questionnaires and Leicester Cough Questionnaire, and basic&#xD;
      lung physiological assessment were performed.&#xD;
&#xD;
      At the end of visit 1, a cough monitor was attached to the subject to monitor cough frequency&#xD;
      for the next 24 hours and this was returned at visit 2.&#xD;
&#xD;
      Visit 2 followed within two weeks after visit 1, during which a full dose capsaicin cough&#xD;
      challenge was performed. Emergency contact details were given towards end of visit 2 should&#xD;
      any adverse events occur.&#xD;
&#xD;
      Telephone call within 48 hours, Day 3 and Day 7: The purpose of these phone calls was to&#xD;
      ensure that the patient had not developed any adverse effects to the capsaicin challenge.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">August 6, 2016</start_date>
  <completion_date type="Anticipated">February 1, 2018</completion_date>
  <primary_completion_date type="Anticipated">February 1, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants who has had significant fall in FEV1 (defined as &gt;20%) within the challenge period</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>By measuring spirometry immediately before and after challenge</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Number of participants who require bronchodilator treatment during capsaicin challenge period</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>Defined as rescue medications - 2 puffs of salbutamol inhaler via spacer</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in %FEV1 predicted during capsaicin challenge period in all subjects</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>By measuring spirometry immediately before and after challenge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The tolerability of inhaled capsaicin in severe asthma</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>By exploring the pattern of termination of challenge in severe asthma</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The number of adverse events in all subjects during and after capsaicin evoked cough challenge</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>by follow up phone calls at 48 hours, 3 days and 7 days to assess AE and SAE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of breathlessness during capsaicin challenge period assessed by using modified Borg scale (mBorg).</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>By calculating Borg immediately before and after challenge to assess level of breathlessness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degree of breathlessness during capsaicin challenge period assessed by using dysnoea Visual Analogue Score (dVAS).</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>By calculating dVAS immediately before and after challenge to assess level of breathlessness.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>by comparing post-BT and no-BT patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The differences in 24-hour cough frequency between patients who have had BT and those who have not.</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>by comparing post-BT and no-BT patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The differences in Leicester cough questionnaire (LCQ) between patients who have had BT and those who have not.</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>by comparing post-BT and no-BT patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The differences in asthma control questionnaire(ACQ) between patients who have had BT and those who have not.</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>by comparing post-BT and no-BT patients</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>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).</measure>
    <time_frame>Through study completion, an average of 6 months</time_frame>
    <description>By comparing with existing data.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">24</enrollment>
  <condition>Asthma Chronic, Cough</condition>
  <arm_group>
    <arm_group_label>Patients without BT</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Post BT</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Inhaled capsaicin cough challenge</intervention_name>
    <arm_group_label>Patients without BT</arm_group_label>
    <arm_group_label>Post BT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged ≥18&#xD;
&#xD;
          -  Person with an established diagnosis of severe asthma&#xD;
&#xD;
          -  All patients should be on British Thoracic Society (BTS) steps 4 or 5&#xD;
&#xD;
          -  Patients who have had bronchial thermoplasty (BT) should be at least 2 months after&#xD;
             their treatment&#xD;
&#xD;
          -  Historical evidence of one of the following:&#xD;
&#xD;
          -  Airway reversibility to a short acting beta-2 agonist of ≥12%&#xD;
&#xD;
          -  Bronchial hyper-responsiveness (PC20&lt;8mg/ml)&#xD;
&#xD;
          -  Fractional exhaled nitric oxide ≥50ppb&#xD;
&#xD;
          -  Peak flow variability &gt;8%&#xD;
&#xD;
          -  Raised serum (≥0.45) or sputum eosinophilia (&gt;3%)&#xD;
&#xD;
          -  Variability in spirometry over 24 months of &gt;20%&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to give informed consent&#xD;
&#xD;
          -  FEV1&lt;50% predicted or &lt; 1 litre&#xD;
&#xD;
          -  Known allergy or intolerance to capsaicin&#xD;
&#xD;
          -  Symptoms of upper respiratory tract infection in the last 1 month which have not&#xD;
             resolved.&#xD;
&#xD;
          -  Lower respiratory tract infection or pneumonia in the last 6 weeks.&#xD;
&#xD;
          -  Current smoker or ex-smoker with ≥10 pack year smoking history, abstinence of ≤6&#xD;
             months&#xD;
&#xD;
          -  Asthma exacerbation in the previous month requiring an increase or starting of an ICS&#xD;
             or OCS&#xD;
&#xD;
          -  Subject has changed asthma medication within the past 4 weeks prior to screening&#xD;
&#xD;
          -  A previous asthma exacerbation requiring Intensive Care Unit (ICU) admission.&#xD;
&#xD;
          -  Significant other pulmonary disorders as the major diagnosis, in particular: pulmonary&#xD;
             embolism, pulmonary hypertension, interstitial lung disease, lung cancer, cystic&#xD;
             fibrosis, emphysema or bronchiectasis.&#xD;
&#xD;
          -  Evidence of vocal cord dysfunction&#xD;
&#xD;
          -  Pregnancy or breast-feeding&#xD;
&#xD;
          -  Use of ACE inhibitors&#xD;
&#xD;
          -  Any centrally acting medication which in the view of the investigator could alter the&#xD;
             sensitivity of the cough reflex*&#xD;
&#xD;
          -  History of psychiatric illness, drug or alcohol abuse which may interfere in the&#xD;
             participation of the trial.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Ran Wang</last_name>
    <email>ranwang1986@googlemail.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>University hospital of South Manchester</name>
      <address>
        <city>Manchester</city>
        <zip>M23 9LT</zip>
        <country>United Kingdom</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ran Wang, Dr</last_name>
      <phone>7557761062</phone>
      <email>ranwang1986@googlemail.com</email>
    </contact>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>September 2017</verification_date>
  <study_first_submitted>August 22, 2017</study_first_submitted>
  <study_first_submitted_qc>September 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 13, 2017</study_first_posted>
  <last_update_submitted>September 11, 2017</last_update_submitted>
  <last_update_submitted_qc>September 11, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">September 13, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>National Health Service, United Kingdom</investigator_affiliation>
    <investigator_full_name>Ran Wang</investigator_full_name>
    <investigator_title>Dr Ran Wang (Chief Investigator); Professor Jacky Smith (PI)</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Asthma</mesh_term>
    <mesh_term>Cough</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Capsaicin</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03281941
org study id: NHSUK
nct id: NCT03281941
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Number of participants who has had significant fall in FEV1 (defined as >20%) within the challenge period
time frame: Through study completion, an average of 6 months
description: By measuring spirometry immediately before and after challenge
measure: Number of participants who require bronchodilator treatment during capsaicin challenge period
time frame: Through study completion, an average of 6 months
description: Defined as rescue medications - 2 puffs of salbutamol inhaler via spacer
measure: Change in %FEV1 predicted during capsaicin challenge period in all subjects
time frame: Through study completion, an average of 6 months
description: By measuring spirometry immediately before and after challenge
measure: The tolerability of inhaled capsaicin in severe asthma
time frame: Through study completion, an average of 6 months
description: By exploring the pattern of termination of challenge in severe asthma
measure: The number of adverse events in all subjects during and after capsaicin evoked cough challenge
time frame: Through study completion, an average of 6 months
description: by follow up phone calls at 48 hours, 3 days and 7 days to assess AE and SAE
measure: Degree of breathlessness during capsaicin challenge period assessed by using modified Borg scale (mBorg).
time frame: Through study completion, an average of 6 months
description: By calculating Borg immediately before and after challenge to assess level of breathlessness.
measure: Degree of breathlessness during capsaicin challenge period assessed by using dysnoea Visual Analogue Score (dVAS).
time frame: Through study completion, an average of 6 months
description: By calculating dVAS immediately before and after challenge to assess level of breathlessness.
measure: 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
time frame: Through study completion, an average of 6 months
description: by comparing post-BT and no-BT patients
measure: The differences in 24-hour cough frequency between patients who have had BT and those who have not.
time frame: Through study completion, an average of 6 months
description: by comparing post-BT and no-BT patients
measure: The differences in Leicester cough questionnaire (LCQ) between patients who have had BT and those who have not.
time frame: Through study completion, an average of 6 months
description: by comparing post-BT and no-BT patients
measure: The differences in asthma control questionnaire(ACQ) between patients who have had BT and those who have not.
time frame: Through study completion, an average of 6 months
description: by comparing post-BT and no-BT patients
measure: 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).
time frame: Through study completion, an average of 6 months
description: By comparing with existing data.
arm group label: Patients without BT
arm group type: Other
arm group label: Post BT
arm group type: Other
intervention type: Other
intervention name: Inhaled capsaicin cough challenge
arm group label: Patients without BT
arm group label: Post BT
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Ran Wang
email: ranwang1986@googlemail.com
facility: 
status: Recruiting
contact: 
country: United Kingdom
responsible party type: Principal Investigator
investigator affiliation: National Health Service, United Kingdom
investigator full name: Ran Wang
investigator title: Dr Ran Wang (Chief Investigator); Professor Jacky Smith (PI)
mesh term: Asthma
mesh term: Cough
mesh term: Capsaicin
sharing ipd: Undecided