The Effect of Deep Inhalation on Mannitol Responsiveness

Phase 3

Completed

• Conditions: Asthma
• Interventions: Procedure: Deep inhalation technique; Procedure: Tidal breathing technique; Drug: Mannitol; Drug: Methacholine

• Registration Number: NCT03505489
• Lead Sponsor: University of Saskatchewan

Brief Summary

The study will assess how the inhalation technique used (deep inhalations versus tidal breathing) influences the results of a mannitol challenge test and a methacholine challenge test, if at all.

Detailed Description

This study will look at airway responsiveness to inhaled methacholine and mannitol administered with and without deep inhalation. This study will also investigate the role of airway inflammation on these responses, using sputum differential cell counts and fractional exhaled nitric oxide.

This is a single center, open label, randomized study. Individuals with stable asthma will be eligible for enrollment. The study will consist of two parts, screening and testing.

Part 1: Screening

Participants will undergo consent procedures and assessments of fractional exhaled nitric oxide levels, airway responsiveness to methacholine and sputum induction. If participants show airway responsiveness to methacholine (i.e. methacholine PC20 16mg/mL), they will be scheduled to undergo the testing part of the study.

Part 2: Testing

Participants will be randomized to undergo two methacholine or two mannitol challenges. Further randomization will occur with respect to whether the standard challenge method or the modified challenge method is performed first.

Study Timeline

• Study First Submitted: 2018-03-29
• Study First Submitted QC: 2018-04-20
• Study First Posted: 2018-04-23
• Study Start: 2018-06-01
• Primary Completion: 2019-04-30
• Study Completion: 2019-04-30
• Status Verified: 2019-05
• Last Update Submitted: 2019-05-14
• Last Update Posted: 2019-05-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 26

Inclusion Criteria

• signed informed consent
• men and women between 18 and 75 years of age
• FEV1 at first measurement of greater than or equal to 65% predicted
• methacholine provocative concentration causing a 20% in FEV1 at screening that is less than or equal to 16mg/ml
• generally good health
• stable asthma

Exclusion Criteria

• respiratory infection within 4 weeks of screening visit
• worsening of asthma within 4 weeks of screening visit
• lung disease other than asthma
• significant medical comorbidity
• current smoker or ex-smoker with significant smoking history
• currently pregnant or breastfeeding

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Mannitol challenge	Deep inhalation technique	Mannitol challenge performed per standard mannitol challenge procedure with deep inhalation technique
Mannitol challenge	Mannitol	Mannitol challenge performed per standard mannitol challenge procedure with deep inhalation technique
Mannitol challenge w/ TBI	Tidal breathing technique	Mannitol challenge performed per standard mannitol challenge procedure except with tidal breathing technique
Methacholine challenge w/ DI	Deep inhalation technique	Methacholine challenge performed per standard 2-minute tidal breathing challenge procedure except with deep inhalation technique
Methacholine challenge	Tidal breathing technique	Methacholine challenge performed per standard 2-minute tidal breathing challenge procedure (tidal breathing technique)
Methacholine challenge	Methacholine	Methacholine challenge performed per standard 2-minute tidal breathing challenge procedure (tidal breathing technique)
Mannitol challenge w/ TBI	Mannitol	Mannitol challenge performed per standard mannitol challenge procedure except with tidal breathing technique
Methacholine challenge w/ DI	Methacholine	Methacholine challenge performed per standard 2-minute tidal breathing challenge procedure except with deep inhalation technique

Primary Outcome Measures

Name	Time	Method
Effect of deep inhalation (versus tidal breathing) on mannitol provocative dose causing a 15% fall in forced expiratory volume in one second (FEV1)	24 hours between mannitol challenges	Shift in mannitol provocative dose causing a 15% fall in forced expiratory volume

Secondary Outcome Measures

Name	Time	Method
Effect of airway inflammation on methacholine and mannitol challenge results-sputum	up to 2 weeks, from baseline to end of study	Collection of sputum at screening - analysis for differential cell counts indicative of degree of baseline airway inflammation
Effect of airway inflammation on methacholine and mannitol challenge results-fractional exhaled nitric oxide	up to 2 weeks, from baseline to end of study	Collection of fractional exhaled nitric oxide at screening - analysis of resulting measurement indicative of degree of baseline airway inflammation
Effect of deep inhalation (versus tidal breathing) on methacholine provocative	24 hours between methacholine challenges	Shift in methacholine provocative dose causing a 20% fall in forced expiratory volume

Trial Locations

Locations (1)

Asthma Research Lab - University of Saskatchewan; 🇨🇦 Saskatoon, Saskatchewan, Canada