Salbutamol, Pharmacogenetics and Breathing Mechanics

Study Overview
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Brief Summary
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Athletes using asthma medications called β2-agonists win a disproportionately high number of medals at Olympic Games. Due to a large variety in the genes that affect how individuals respond to β2-agonists, the investigators will look at variations in the genetic response to these medications by dividing athletes into high-responders and low-responders. The investigators will then compare athletic performance after the inhalation of β2-agonists to placebo. Furthermore, the investigators will analyze the effect of β2-agonists on breathing mechanics. Due to differences in their anatomy females may decrease the energy needed for breathing during high-intensity exercise to a greater extent compared to male athletes after the inhalation of β2-agonists.

Official Title
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The Pharmacogenetic Effects of Inhaled Salbutamol on Breathing Mechanics and Cycling Performance

Conditions
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Bronchoconstriction, Inhaled Salbutamol, Cycling Performance

Intervention / Treatment
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* Drug: Salbutamol
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: trained, experienced cyclists maximal oxygen consumption of at least 50ml/kg/min or 4l/min for women; and 60ml/kg/min or 5l/min for men athletes with and without exercise-induced bronchoconstriction Exclusion Criteria: any uncontrolled heart or lung condition maximal oxygen consumption of less than 50ml/kg/min or 4L/min for women; and less than 60ml/kg/min or 5L/min for men pregnancy smoking

Ages Eligible for Study
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Minimum Age: 19 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Salbutamol<br>400ug of salbutamol (one single inhalation) will be inhaled 60min prior to the begin of a time trial. Mean power output during the following 10km time trial will be described to 1600ug salbutamol and placebo. | Drug: Salbutamol<br>* 60 minutes prior to the start of a 10km cycling time trial on a bike ergometer, subjects will inhale either 400ug of salbutamol 1600ug of salbutamol or 400ug of placebo in a randomly assigned manner in a single dose.<br>* Other names: ventolin;|
| Placebo Comparator: Placebo<br>400ug of placebo (one single inhalation) will be inhaled 60min prior to the begin of a time trial. Mean power output during the following 10km time trial will be described to 400ug and 1600ug salbutamol. | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of inhaled salbutamol on mean power output during cycling performance in female and male athletes | Athletes perform a two time trials, each on a separate day. The time trials are performed 60min after the inhalation of salbutamol or placebo. | Mean power output is assessed over the duration of a 10km time trial (start of time trial until completion of time trial) on a bike ergometer. | 
| The effect of inhaled salbutamol on work of breathing (WOB) and expiratory flow limitation (EFL) in female and male athletes | EFL and WOB will be assessed with the help of an esophageal balloon and mouth pressure. | WOB and EFL will be assessed during an incremental exercise test. Exercise will start at 0 Watts and will then be increased every 2.5min by 30 Watts until maximal exertion. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The effect of inhaled salbutamol on minute ventilation in asthmatic and non-asthmatic trained, female and male cyclists |  | Minute ventilation will be assessed during two 10km time trials (one time trial will be started 60min after the inhalation of salbutamol, the second time trial will be started 60min after the inhalation of placebo). | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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exercise-induced bronchoconstriction (EIB), inhaled salbutamol, performance enhancing, cycling