Physiology of Cough in Asthma: Comparison of Sensory-Mechanical Responses to Mannitol and Methacholine Challenge Tests

• ClinicalTrials.gov Identifier: NCT01064245
• Recruitment Status: Completed
• First Posted: February 8, 2010
• Last Update Posted: February 28, 2022
• Sponsor: Dr. Diane Lougheed
• Collaborators: The Ontario Thoracic Society of the Ontario Lung Association; Queen's University (William M Spear / Start Memorial Fund)
• Information provided by (Responsible Party): Dr. Diane Lougheed, Queen's University

Tracking Information

• First Submitted Date: February 1, 2010
• First Posted Date: February 8, 2010
• Last Update Posted Date: February 28, 2022
• Actual Study Start Date: February 1, 2010
• Actual Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: February 5, 2010): PD15 (15% fall in forced expiratory volume in one second (FEV1) from baseline during challenge test visits) [ Time Frame: baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test) ]
• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 5, 2010)

• %ΔFEV1 (percentage change in forced expiratory volume in one second) [ Time Frame: baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test) ]
• Plateau response [ Time Frame: baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test) ]
• Dose-response slope [ Time Frame: baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test) ]
• Expiratory Flow Limitation (EFL) [ Time Frame: baseline and several time points collected throughout test (high-dose methacholine challenge test or mannitol challenge test) ]

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Physiology of Cough in Asthma: Comparison of Sensory-Mechanical Responses to Mannitol and Methacholine Challenge Tests
• Official Title: Physiology of Cough in Asthma: Comparison of Sensory-Mechanical Responses to Mannitol and Methacholine Challenge Tests
• Brief Summary: Cough is a common, disruptive and at times disabling symptom which often prompts patients to seek medical attention. Determining the cause(s) of chronic cough can be challenging, and costly. Asthma and other airway disorders are among the most common causes of chronic cough; and cough can be the sole symptom of asthma. Little is known about why some patients with asthma primarily cough and do not develop the other symptoms of asthma such as shortness of breath or wheeze. Improved understanding of the reasons for these different manifestations may lead to new and more effective treatment strategies. We have notices differences in pressure measurements inside the chest in patients who mostly cough during induced bronchoconstriction, which might be part of the explanation for varying symptoms. This study will compare lung mechanical responses during methacholine and mannitol-induced induced airway narrowing between typical asthma, cough variant asthma (CVA) and an airway inflammatory disorder that is not asthma.The purpose of this research is to explore the pathophysiology and sensory-mechanics of cough in individuals with asthma, CVA and methacholine-induced cough but normal airway sensitivity using mannitol and high-dose methacholine bronchoprovocation testing.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Basic Science

Condition

• Asthma
• Cough Variant Asthma

Intervention

• Drug: high-dose methacholine challenge test
  nebulized liquid inhalation, 0.0625 - 256 mg/mL, doubling doses
  Other Name: Provocholine
• Other: mannitol challenge test
  inhaled powder, 0 - 635 mg, increments of 5,10, 20 and 40 mg
  Other Name: Aridol

Study Arms

• Experimental: Cough Variant Asthma
  Those diagnosed with cough variant asthma.
  Interventions:

  • Drug: high-dose methacholine challenge test
  • Other: mannitol challenge test
• Experimental: Asthma
  Those with diagnosed asthma.
  Interventions:

  • Drug: high-dose methacholine challenge test
  • Other: mannitol challenge test

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: February 9, 2022): 29
• Original Estimated Enrollment (submitted: February 5, 2010): 24
• Actual Study Completion Date: December 31, 2021
• Actual Primary Completion Date: December 31, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Subjects with asthma or suspected CVA who have previously participated in or who have expressed interest in participating in studies will be invited to participate in the study. Previous treatment with inhaled or systemic corticosteroids is not an exclusion criterion, but medication use will be recorded and examined in the analysis.

Exclusion Criteria:

1. An exacerbation necessitating any alteration in medication, emergency department visit or hospitalizations within the previous 4 weeks;
2. Inability to perform acceptable quality spirometry;

3. Medical contraindications to methacholine challenge testing 35, including:

   1. Severe airflow limitation (FEV1 <50% predicted or <1.0 L);
   2. Heart attack or stroke in last 3 months;
   3. Uncontrolled hypertension, systolic BP > 200 or diastolic BP > 100;
   4. Known aortic aneurysm;
   5. Moderate airflow limitation < 60% predicted or <1.5 L);
   6. Inability to perform acceptable quality spirometry;
   7. Current use of cholinesterase inhibitor medication (for myasthenia gravis); and
   8. Pregnant or nursing mothers.
4. Smoking history in excess of 10 pack years;

5. Medical contraindications to mannitol challenge testing, including:

   1. Aortic or cerebral aneurysm;
   2. Uncontrolled hypertension; and
   3. Myocardial infarction or a cerebral vascular accident in the previous six months).
6. Women who are pregnant or breastfeeding because the effects of a possible hyperresponsiveness reaction to mannitol in mothers and/or fetuses are unknown and many compounds are excreted in human milk therefore caution should be taken.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 65 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Canada

Administrative Information

• NCT Number: NCT01064245
• Other Study ID Numbers: 2010-01
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Dr. Diane Lougheed, Queen's University
• Original Responsible Party: Diane Lougheed, MD FRCP(C), Queen's University and Kingston General Hospital
• Current Study Sponsor: Dr. Diane Lougheed
• Original Study Sponsor: Queen's University

Collaborators

• The Ontario Thoracic Society of the Ontario Lung Association
• Queen's University (William M Spear / Start Memorial Fund)

Investigators

• Principal Investigator: Diane Lougheed, MD; Queen's University
• Principal Investigator: Scott Turcotte; Queen's University

• PRS Account: Queen's University
• Verification Date: February 2022