Regular Use Tiotropium and Tolerance to Bronchoprotection in Mild Asthma

Phase 4

Completed

• Conditions: Asthma
• Interventions: Drug: Tiotropium Bromide; Drug: Matching placebo

• Registration Number: NCT05113615
• Lead Sponsor: University of Saskatchewan

Brief Summary

The study will assess if regular use of tiotropium (i.e. daily) results in loss of bronchoprotection against methacholine induced bronchoconstriction in those with mild asthma.

Detailed Description

A single dose of an inhaled muscarinic antagonist will protect against methacholine induced bronchoconstriction and increase the dose of methacholine required to cause bronchoconstriction about 4 doubling doses. Beta agonist bronchodilators also shift the dose response curve to the right but the protection against methacholine induced bronchoconstriction is lost (i.e. tolerance develops) with regular use. This study will determine if bronchoprotection is lost following regular use of tiotropium.

This will be a randomized, double-blind placebo controlled study to assess the development of tolerance following regular use of tiotroium in a population of mild asthmatics.

Tiotropium will be administered at the clinically recommended dose (5mcg/day) for a total of 8 days. Methacholine challenges will be performed at baseline (pre-treatment), at one hour post first dose and on day 8, one hour after the final dose. The same will dosing schedule and assessments will occur with an identical placebo inhaler.

Study Timeline

• Study First Submitted: 2021-10-28
• Study First Submitted QC: 2021-10-28
• Study First Posted: 2021-11-09
• Study Start: 2021-12-13
• Status Verified: 2022-05
• Primary Completion: 2022-05-06
• Study Completion: 2022-05-06
• Last Update Submitted: 2022-05-16
• Last Update Posted: 2022-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• diagnosis of asthma
• asthma is currently well controlled using only occasional bronchodilators
• baseline lung function (FEV1) is greater than 65% of the predicted value
• exhibit bronchoconstriction to inhaled methacholine at a dose of 200mcg or less

Exclusion Criteria

• women who are pregnant or breastfeeding.
• diagnosis of another lung condition or medical condition that would pose a risk to the participant if enrolled in the study
• current smokers of nicotine products (e.g., cigarettes).
• users of cannabis or other inhaled recreational products (e.g., e-cigarettes or other vaping products) on a daily basis
• respiratory infection within 4 weeks of entering the study
• use of any anticholinergic agent within 30 days prior to the beginning of the study (e.g., ipratropium or the study treatment tiotropium).
• known hypersensitivity to tiotropium bromide or components of tiotropium formulation (e.g., benzalkonium chloride), to atropine or its derivatives.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
tiotropium bromide	Tiotropium Bromide	tiotropium bromide inhaler (Spiriva Respimat) will be used once daily (2 puffs) for a total of 8 days
Matching placebo	Matching placebo	matching placebo inhaler will be used once daily (2 puffs) for a total of 8 days

Primary Outcome Measures

Name	Time	Method
Methacholine PD20	one hours post final dose	dose of methacholine required to induce a 20% fall in FEV1 (volume of air forcefully exhaled in the first second following a full inhalation)

Trial Locations

Locations (1)

Asthma Research Lab University of Saskatchewan Room 346 Ellis Hall; 🇨🇦 Saskatoon, Saskatchewan, Canada