Regular Use Tiotropium and Tolerance to Bronchoprotection in Mild Asthma

Daily Dosing of Tiotropium and Tolerance to Bronchoprotection Against Methacholine Challenge

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Drug: Tiotropium Bromide; Drug: Matching placebo

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 Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Saskatchewan
    • Saskatoon, Saskatchewan, Canada, S7N 0W8
      • Asthma Research Lab University of Saskatchewan Room 346 Ellis Hall

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: tiotropium bromide; tiotropium bromide inhaler (Spiriva Respimat) will be used once daily (2 puffs) for a total of 8 days	Drug: Tiotropium Bromide; respimat inhaler 2.5mcg/puff; Other Names: Spiriva Respimat
Placebo Comparator: Matching placebo; matching placebo inhaler will be used once daily (2 puffs) for a total of 8 days	Drug: Matching placebo; matching placebo Respimat inhaler

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Methacholine PD20	dose of methacholine required to induce a 20% fall in FEV1 (volume of air forcefully exhaled in the first second following a full inhalation)	pre treatment
Methacholine PD20	dose of methacholine required to induce a 20% fall in FEV1 (volume of air forcefully exhaled in the first second following a full inhalation)	one hour post first dose
Methacholine PD20	dose of methacholine required to induce a 20% fall in FEV1 (volume of air forcefully exhaled in the first second following a full inhalation)	one hours post final dose

Collaborators and Investigators

• Sponsor: University of Saskatchewan

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2021
• Primary Completion (Actual): May 6, 2022
• Study Completion (Actual): May 6, 2022

Study Registration Dates

• First Submitted: October 28, 2021
• First Submitted That Met QC Criteria: October 28, 2021
• First Posted (Actual): November 9, 2021

Study Record Updates

• Last Update Posted (Actual): May 23, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: tolerance; tiotropium; bronchoprotection; methacholine PD20
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Parasympatholytics; Autonomic Agents; Peripheral Nervous System Agents; Cholinergic Antagonists; Cholinergic Agents; Anticonvulsants; Bronchodilator Agents; Anti-Asthmatic Agents; Respiratory System Agents; Tiotropium Bromide; Bromides
• Other Study ID Numbers: Bio ID 2985

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