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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03620422
Recruitment Status : Completed
First Posted : August 8, 2018
Last Update Posted : February 17, 2020
Sponsor:
Collaborators:
Pharmaxis
AllerGen NCE Inc.
Information provided by (Responsible Party):
McMaster University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Asthma Cough Other: Mannitol Drug: Salbutamol 5mg/mL Other: Sodium Chloride 0.9% Inhl 3Ml Not Applicable

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

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 40 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This is a mechanistic study. The first part of the study (mild allergic asthmatics and healthy controls) is to determine reproducibility of dose responses to mannitol-induced coughs. The second part of the study (mild asthmatics only) is to determine the effect of salbutamol on mannitol-induced coughs. Salbutamol or placebo will be delivered following a mannitol cough challenge in a randomized, double-blind crossover design.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Other
Official Title: Mannitol-Induced Cough Challenge in Healthy Controls and Subjects With Mild Allergic Asthma
Actual Study Start Date : January 11, 2019
Actual Primary Completion Date : January 31, 2020
Actual Study Completion Date : January 31, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Asthma Cough

Arm Intervention/treatment
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 Name: 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 Name: Aridol

Other: Sodium Chloride 0.9% Inhl 3Ml
Nebulized 0.9% saline given prior to Mannitol-Induced Cough Challenge
Other Name: 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 Name: Aridol

Drug: Salbutamol 5mg/mL
Nebulized salbutamol given prior to Mannitol-Induced Cough Challenge
Other Name: Active Comparator




Primary Outcome Measures :
  1. ED50 dose response curve [ Time Frame: Through study completion, an average of one year ]
    Median effective dose


Secondary Outcome Measures :
  1. ED50 (post-bronchodilator) dose response curve [ Time Frame: Through study completion, an average of one year ]
    Median effective dose



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03620422


Locations
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Canada, Ontario
McMaster University
Hamilton, Ontario, Canada, L8N 3Z5
Sponsors and Collaborators
McMaster University
Pharmaxis
AllerGen NCE Inc.
Investigators
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Principal Investigator: Gail Gauvreau, PhD McMaster University
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Responsible Party: McMaster University
ClinicalTrials.gov Identifier: NCT03620422    
Other Study ID Numbers: McMaster-MICC4657
First Posted: August 8, 2018    Key Record Dates
Last Update Posted: February 17, 2020
Last Verified: March 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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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
Keywords provided by McMaster University:
Mannitol
Bronchoconstriction
Airway nerve function
Cough
Diagnostic Test
Osmolarity
Salbutamol
Additional relevant MeSH terms:
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Asthma
Cough
Bronchial Diseases
Respiratory Tract Diseases
Lung Diseases, Obstructive
Lung Diseases
Respiratory Hypersensitivity
Hypersensitivity, Immediate
Hypersensitivity
Immune System Diseases
Respiration Disorders
Signs and Symptoms, Respiratory
Mannitol
Albuterol
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Asthmatic Agents
Respiratory System Agents
Tocolytic Agents
Reproductive Control Agents
Adrenergic beta-2 Receptor Agonists
Adrenergic beta-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Diuretics, Osmotic
Diuretics