Regular Use Tiotropium and Tolerance to Bronchoprotection in Mild Asthma

Study Overview
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Brief Summary
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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
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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.

Official Title
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Daily Dosing of Tiotropium and Tolerance to Bronchoprotection Against Methacholine Challenge

Conditions
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Asthma

Intervention / Treatment
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* Drug: Tiotropium Bromide
* Drug: Matching placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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tiotropium, bronchoprotection, tolerance, methacholine PD20