The Effects of Salbutamol on Mannitol Induced Cough Responses in Healthy Controls

NCT04565847 | Completed Phase 2

• 1 other identifier: McMaster-COMA-11537
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

Brief Summary

The study aim is to investigate if changes in osmolarity using mannitol challenge can evoke coughing healthy controls with no evidence of bronchoconstriction (PC20\>16mg/ml or mannitol PD15 \> 635 mg, or \< 10% incremental fall in FEV1 between consecutive mannitol doses) and if salbutamol can affect this. This is a double-blind, placebo-controlled analysis in healthy controls assessing the effects of salbutamol on mannitol induced cough.

Conditions

Cough

Outcome Measures

Primary Outcomes (1)

• Primary Outcome - Emax

  The effect of salbutamol on mannitol induced coughs Emax - the maximum number of coughs at any dose of mannitol.

  Through study completion, an average of 1 year

Secondary Outcomes (5)

• Cough dose response curves

  Through study completion, an average of 1 year

• ED50

  Through study completion, an average of 1 year

• C2

  Through study completion, an average of 1 year

• C5

  Through study completion, an average of 1 year

• Cumulative number of coughs

  Through study completion, an average of 1 year

Study Arms (2)

Healthy Control - Active Arm

ACTIVE COMPARATOR

Healthy Controls Mannitol-Induced Cough Challenges on Visit 2 to determine elligibility (cough response). Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. Nebulized salbutamol (5mg/mL) given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4.

Drug: Salbutamol 5mg/mL

Healthy control - Placebo Arm

PLACEBO COMPARATOR

Healthy Controls Mannitol-Induced Cough Challenges on Visit 2 to determine elligibility (cough response). Mannitol delivered via inhalation. Dosage: 0, 5, 10, 20, 40 mg capsules. 80 and 160 mg doses delivered with two and four capsules, respectively. Nebulized 0.9% Saline given prior to Mannitol-Induced Cough Challenges on Visit 3 or 4.

Drug: Sodium Chloride 0.9% Inhl 3Ml

Interventions

Salbutamol 5mg/mL DRUG

Nebulized salbutamol given prior to Mannitol-Induced Cough Challenge

Also known as: Ventolin nebuliser

Healthy Control - Active Arm

Sodium Chloride 0.9% Inhl 3Ml DRUG

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

Also known as: Placebo Comparator

Healthy control - Placebo Arm

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.
• No airway hyperresponsiveness as determined by methacholine PC20\>16mg/ml or mannitol PD15 \> 635 mg, or \< 10% incremental fall in FEV1 between consecutive mannitol doses.
• Fall in FEV1 of ≤ 5% after any mannitol dose during mannitol challenge compared to baseline FEV1 at 0 mg at screening mannitol challenge (Visit 2).
• Baseline FEV1≥ 80% of the predicted value.
• 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
• Pregnancy or breastfeeding.
• 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
• Use of caffeine-containing products within 4 hours of study visits
• Use of 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.
• Unwillingness or inability to comply with the study protocol for any other reason

Sponsors & Collaborators

• McMaster University: lead

Study Sites (2)

McMaster Cardio-Respiratory Research Lab

Hamilton, Ontario, L8N 3Z5, Canada

Location

McMaster University

Hamilton, Ontario, L8N 3Z5, Canada

Location

MeSH Terms

Conditions

Cough

Interventions

Albuterol; Sodium Chloride

Condition Hierarchy (Ancestors)

Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

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

Study Officials

• Gail Gauvreau, PhD

  McMaster University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor Department of MEdicine

Model Details: albutamol or placebo will be delivered following a mannitol cough challenge in a randomized, double-blind crossover design.

Study Record Dates

• First Submitted: August 17, 2020
• First Posted: September 25, 2020
• Study Start: November 30, 2020
• Primary Completion: December 16, 2021
• Study Completion: December 16, 2021
• Last Updated: June 16, 2022

Record last verified: 2022-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2)