Determining Baseline Respiratory Duty Cycles in Subjects With and Without Airway Hyperresponsiveness

The study investigates the inspiratory duty cycle in subjects with and without airway hyper-responsiveness both at rest and during a bronchoprovocation challenge. The primary goal is to determine an average inspiratory duty cycle for standard use in the calculation of bronchoprovocation test results.

Study Overview

• Status: Completed
• Conditions: Airway Hyper Responsiveness
• Intervention / Treatment: Procedure: Volumetric methacholine challenge unmodified; Procedure: Modified volumetric methacholine challenge

Detailed Description

At least fifteen subjects with airway hyper-responsiveness and fifteen without airway hyper-responsiveness will be recruited to participate in this randomized, crossover study. Subjects will complete 2 methacholine challenges at least 24 hours apart. One methacholine challenge will entail the volumetric method using a vibrating mesh nebulizer. The second methacholine challenge will be performed identically except that the nebulizer will be fitted onto an ultrasonic nebulizer so as to measure the inspiratory duty cycle throughout the bronchoprovocation challenge.

• Study Type: Interventional
• Enrollment (Actual): 34
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Asthma Research Lab - University of Saskatchewan

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Must be 18 years of age or older
• Participants with airway hyper-responsiveness must have a positive methacholine challenge
• Forced expiratory volume (FEV1) of at least 65% of predicted (based on age, height, and gender)
• Participants without airway hyper-responsiveness must have a negative methacholine challenge
• All participants must avoid strenuous exercise on test days
• No short-acting beta-2 agonist use within 6 hours of study visit

Exclusion Criteria:

• Participants without known airway hyper-responsiveness cannot have a current or historical respiratory condition (e.g. asthma, allergic rhinitis)
• Participants cannot be taking long-acting bronchodilators
• Participants cannot be pregnant or lactating
• Participants cannot have cardiovascular problems

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Volumetric methacholine challenge; Methacholine challenge performed per the volumetric method using an Aerogen Solo vibrating mesh nebulizer	Procedure: Volumetric methacholine challenge unmodified; Bronchoprovocation challenge performed per volumetric method
ACTIVE_COMPARATOR: Methacholine challenge with spirometer; Methacholine challenge performed per the volumetric method using an Aerogen Solo vibrating mesh nebulizer fitted with an ultrasonic spirometer	Procedure: Modified volumetric methacholine challenge; Bronchoprovocation challenge performed per volumetric method modified to include use of ultrasonic spirometer fitted with vibrating mesh nebulizer

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Average inspiratory duty cycle in subjects with airway hyper-responsiveness measured using ultrasonic spirometer and tidal breathing	The inspiratory duty cycles measured for each participant (in duplicate over at least 24 hours) will be averaged for all participants with airway hyper-responsiveness and for all participants without airway-hyperresponsiveness	24 hours
Average inspiratory duty cycle in subjects without airway hyper-responsiveness	The inspiratory duty cycles measured for each participant (in duplicate over at least 24 hours) will be averaged for all participants without airway hyper-responsiveness	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Within-subject variability in inspiratory duty cycle measured using ultrasonic spirometer and tidal breathing during room air inhalation	Repeat measurements of inspiratory duty cycle during tidal breathing of room air collected at least 24 hours apart	24 hours
Between-subject variability within subject group (i.e. airway hyper-responsiveness group)	Investigation of whether subjects differ in their inspiratory duty cycles (within their respective study group)	1 hour
Variability in inspiratory duty cycle within subjects when inhaling room air versus an aerosol while using tidal breathing through an ultrasonic spirometer	Investigation of whether participants differ in their inspiratory duty cycle when inhaling room air versus a saline vapor (i.e. does an aerosol influence people's breathing pattern)	1 hour
Within-subject variability in provocative dose of methacholine causing a 20% fall in forced expiratory volume (PD20) between repeat methacholine challenges	Repeat PD20 measures collected for each participant will be compared to determine if there is any significant within-subject variability in PD20	24 hours
Variability in inspiratory duty cycle with progressive airway constriction induced through methacholine challenge testing	The inspiratory duty cycle in each subject will be measured throughout a methacholine challenge during each inhalation period, which will allow for determination of whether the inspiratory duty cycle changes with the progressive airway constriction (or lack thereof) induced through methacholine challenge testing	24 hours
Variability in in inspiratory duty cycle between airway hyper-responsiveness group and group without airway-hyperresponsiveness	Analysis of variance to determine whether subjects differ in their inspiratory duty cycles based on their status as having or as not having airway-hyperresponsiveness	1 hour
Within-subject variability in inspiratory duty cycle measured using ultrasonic spirometer and tidal breathing during saline inhalation	Repeat measurements of inspiratory duty cycle during tidal breathing of nebulized saline collected at least 24 hours apart	24 hours
Between-subject variability within subject group (no airway hyper-responsiveness group)	Investigation of whether subjects differ in their inspiratory duty cycles (within their respective study group)	1 hour

Collaborators and Investigators

• Sponsor: University of Saskatchewan

Study record dates

Study Major Dates

• Study Start (ACTUAL): May 14, 2019
• Primary Completion (ACTUAL): June 30, 2019
• Study Completion (ACTUAL): June 30, 2019

Study Registration Dates

• First Submitted: June 11, 2019
• First Submitted That Met QC Criteria: June 25, 2019
• First Posted (ACTUAL): June 28, 2019

Study Record Updates

• Last Update Posted (ACTUAL): March 27, 2020
• Last Update Submitted That Met QC Criteria: March 25, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Hypersensitivity, Immediate; Hypersensitivity; Respiratory Hypersensitivity; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Agents; Cholinergic Agonists; Respiratory System Agents; Miotics; Parasympathomimetics; Bronchoconstrictor Agents; Muscarinic Agonists; Methacholine Chloride
• Other Study ID Numbers: TiTtot-2019

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