Mannitol-Induced Cough Challenge in Healthy Controls and Subjects With Mild Allergic Asthma (MICC)

February 12, 2020 updated by: McMaster University
The study aim is to investigate if changes in osmolarity using mannitol challenge can evoke coughing reproducibly in mild allergic asthmatics compared with healthy controls and if salbutamol can affect this. Phase 1 of this study is a reproducibility analysis of cough dose response to mannitol in a cohort of mild allergic asthmatics and healthy controls. Phase 2 is a double-blind, placebo-controlled analysis in mild allergic asthmatics assessing the effects of salbutamol on mannitol induced cough.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study will have a maximum of 4 visits separated by at least 24 hours. The first 2 visits will determine eligibility. All eligible subjects will be invited back for a third visit, and only subjects with mild allergic asthma will be invited back for a fourth visit.

Screening Period (Visits 1 and 2) - For All Subjects Eligible subjects will be identified during the initial screening procedures with measures of spirometry, hyperresponsiveness to methacholine, complete history, physical examination, allergen skin test, and mannitol cough challenge. The screening procedures will be conducted over 2 separate visits.

Reproducibility (Visit 3) - For Healthy Controls Ten normal healthy controls meeting study eligibility will return for visit 3. This visit must be at least 24h after the mannitol test at visit 1. These data will be used for assessing reproducibility of the mannitol induced coughs; Emax and the median effective dose (ED50).

Effects of Salbutamol (Visit 3 and 4) - For Mild Allergic Asthma Subjects Ten subjects with mild allergic asthma will return for visit 3 and 4. These visits must be at least 24h apart and no longer than 7 days. Mild allergic asthmatics will first receive salbutamol 2.5mg or saline placebo via a nebuliser and 15 mins later the forced expiratory volume at one second (FEV1) measured. Subjects will then undergo a mannitol cough challenge exactly like the previous mannitol cough challenges. These data will be used for determining the effects of salbutamol on mannitol-induced bronchoconstriction and cough.

Visit Windows Each visit must be separated by a minimum of 24 hours, and a maximum of 7 days. Study visits can be performed in the morning or afternoon, however for each subject the timing should be consistent with Visits 2 at the same time of day ± 2 hours

Study Type

Interventional

Enrollment (Actual)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Hamilton, Ontario, Canada, L8N 3Z5
        • McMaster University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 65 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Able to understand and give written informed consent
  2. Male and female volunteers 18 through 65 years of age.
  3. Positive skin-prick test to common aeroallergens (mild allergic asthmatic subjects)
  4. Asthma as determined by methacholine provocative concentration causing a 20% fall (PC20) ≤16 mg/ml for mild allergic asthmatic subjects; no airway hyperresponsiveness as determined by methacholine PC20>16mg/ml for normal healthy controls.
  5. Baseline FEV1 ≥ 70% of the predicted value for mild allergic asthmatic subjects; baseline FEV1≥ 80% of the predicted value for normal healthy controls.
  6. Demonstrate cough response to inhaled mannitol

Exclusion Criteria:

  1. Current or former smoker with >10-pack-year history
  2. Current or previous history of other significant respiratory disease
  3. Significant systemic disease, including history of current malignancy or autoimmune disease
  4. Asthma exacerbation or upper/lower respiratory tract infection within the previous 8 weeks
  5. Pregnancy
  6. Use of corticosteroids within 28 days prior to the first study visit.
  7. Use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hours of study visits or aspirin with 7 days of study visits
  8. Use of antihistamines including those in cold and allergy medications within 72 hours of study visits
  9. Chronic use of other medication for treatment of allergic lung disease other than short-acting β2-agonists.
  10. Use of caffeine-containing products within 4 hours of study visits
  11. Use of Angiotensin converting enzyme inhibitors (ACE inhibitors)
  12. Any centrally acting medication which in the view of the investigator could alter the sensitivity of the cough reflex including but not restricted to tricyclic anti-depressants, pregabalin, gabapentin, codeine, tramadol, or any other opioid.
  13. Lung disease other than mild to moderate allergic asthma, for mild allergic asthmatic subjects; no lung disease for normal healthy controls.
  14. Unwillingness or inability to comply with the study protocol for any other reason.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: OTHER
  • Allocation: RANDOMIZED
  • Interventional Model: CROSSOVER
  • Masking: QUADRUPLE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
OTHER: Healthy Controls
Mannitol-Induced Cough Challenges on Visit 2 and 3. Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively.
Other: Mannitol
Mannitol-Induced Cough Challenge
Other Names:
  • Aridol
PLACEBO_COMPARATOR: Mild Allergic Asthmatics (Saline)
Mannitol-Induced Cough Challenges on Visit 2, 3 and 4. Nebulized placebo (Sodium Chloride 0.9% Inhl 3Ml) given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4. Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively.
Other: Mannitol
Mannitol-Induced Cough Challenge
Other Names:
  • Aridol
Other: Sodium Chloride 0.9% Inhl 3Ml
Nebulized 0.9% saline given prior to Mannitol-Induced Cough Challenge
Other Names:
  • Placebo Comparator
ACTIVE_COMPARATOR: Mild Allergic Asthmatics (Salbutamol)
Mannitol-Induced Cough Challenges on Visit 2, 3 and 4. Nebulized salbutamol (5mg/mL) given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4. Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively.
Other: Mannitol
Mannitol-Induced Cough Challenge
Other Names:
  • Aridol
Drug: Salbutamol 5mg/mL
Nebulized salbutamol given prior to Mannitol-Induced Cough Challenge
Other Names:
  • Active Comparator

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ED50 dose response curve
Time Frame: Through study completion, an average of one year
Median effective dose
Through study completion, an average of one year

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
ED50 (post-bronchodilator) dose response curve
Time Frame: Through study completion, an average of one year
Median effective dose
Through study completion, an average of one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

McMaster University

Collaborators

Pharmaxis
AllerGen NCE Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

January 11, 2019

Primary Completion (ACTUAL)

January 31, 2020

Study Completion (ACTUAL)

January 31, 2020

Study Registration Dates

First Submitted

July 9, 2018

First Submitted That Met QC Criteria

August 3, 2018

First Posted (ACTUAL)

August 8, 2018

Study Record Updates

Last Update Posted (ACTUAL)

February 17, 2020

Last Update Submitted That Met QC Criteria

February 12, 2020

Last Verified

March 1, 2019

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • McMaster-MICC4657

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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