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

NCT03620422 | Completed

• 1 other identifier: McMaster-MICC4657
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma; Cough

Keywords

Mannitol; Bronchoconstriction; Airway nerve function; Cough; Diagnostic Test; Osmolarity; Salbutamol

Outcome Measures

Primary Outcomes (1)

• ED50 dose response curve

  Median effective dose

  Through study completion, an average of one year

Secondary Outcomes (1)

• ED50 (post-bronchodilator) dose response curve

  Through study completion, an average of one year

Study Arms (3)

Healthy Controls

OTHER

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

Mild Allergic Asthmatics (Saline)

PLACEBO COMPARATOR

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; Other: Sodium Chloride 0.9% Inhl 3Ml

Mild Allergic Asthmatics (Salbutamol)

ACTIVE COMPARATOR

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; Drug: Salbutamol 5mg/mL

Interventions

Mannitol OTHER

Mannitol-Induced Cough Challenge

Also known as: Aridol

Healthy Controls; Mild Allergic Asthmatics (Salbutamol); Mild Allergic Asthmatics (Saline)

Salbutamol 5mg/mL DRUG

Nebulized salbutamol given prior to Mannitol-Induced Cough Challenge

Also known as: Active Comparator

Mild Allergic Asthmatics (Salbutamol)

Sodium Chloride 0.9% Inhl 3Ml OTHER

Nebulized 0.9% saline given prior to Mannitol-Induced Cough Challenge

Also known as: Placebo Comparator

Mild Allergic Asthmatics (Saline)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Able to understand and give written informed consent
• Male and female volunteers 18 through 65 years of age.
• Positive skin-prick test to common aeroallergens (mild allergic asthmatic subjects)
• 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.
• Baseline FEV1 ≥ 70% of the predicted value for mild allergic asthmatic subjects; baseline FEV1≥ 80% of the predicted value for normal healthy controls.
• Demonstrate cough response to inhaled mannitol

You may not qualify if:

• Current or former smoker with \>10-pack-year history
• Current or previous history of other significant respiratory disease
• Significant systemic disease, including history of current malignancy or autoimmune disease
• Asthma exacerbation or upper/lower respiratory tract infection within the previous 8 weeks
• Pregnancy
• Use of corticosteroids within 28 days prior to the first study visit.
• Use of nonsteroidal anti-inflammatory drugs (NSAIDs) within 48 hours of study visits or aspirin with 7 days of study visits
• Use of antihistamines including those in cold and allergy medications within 72 hours of study visits
• Chronic use of other medication for treatment of allergic lung disease other than short-acting β2-agonists.
• Use of caffeine-containing products within 4 hours of study visits
• Use of Angiotensin converting enzyme inhibitors (ACE inhibitors)
• 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.
• Lung disease other than mild to moderate allergic asthma, for mild allergic asthmatic subjects; no lung disease for normal healthy controls.
• Unwillingness or inability to comply with the study protocol for any other reason.

Sponsors & Collaborators

• McMaster University: lead
• Syntara: collaborator
• AllerGen NCE Inc.: collaborator

Study Sites (1)

McMaster University

Hamilton, Ontario, L8N 3Z5, Canada

Location

MeSH Terms

Conditions

Asthma; Cough

Interventions

Mannitol; Albuterol; Sodium Chloride

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates; Ethanolamines; Amino Alcohols; Amines; Phenethylamines; Ethylamines; Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Gail Gauvreau, PhD

  McMaster University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: July 9, 2018
• First Posted: August 8, 2018
• Study Start: January 11, 2019
• Primary Completion: January 31, 2020
• Study Completion: January 31, 2020
• Last Updated: February 17, 2020

Record last verified: 2019-03

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)