REPLACE: Can Exercise Replace Inhaled Corticosteroid Treatment in Asthma? A RCT

Study Overview
=================
Brief Summary
-----------------
To evaluate if physical exercise intervention leads to an improved asthma control as measured by Asthma Control Questionnaire (ACQ-5) in such a magnitude that inhaled corticosteroid can be reduces in asthmatics.

Detailed Description
-----------------
At least 102 asthmatics will be randomized 2:1 (2 to training group; 1 to control) and undergo 6 months of intervention or usual lifestyle. Subjects must have confirmed asthma diagnosis, on a stable treatment with inhaled corticosteroid, symptomatic and untrained. At enrollment and during the study asthma medicine is adjusted based on asthma symptoms evaluated by ACQ-5. 6 treatment steps are pre-defined, and if well controlled asthma, subjects are down-titrated one step, if uncontrolled, subjects are uptitrated one step.

Official Title
-----------------
REPLACE: Can Exercise Replace Inhaled Corticosteroid Treatment in Asthma? A Randomized Clinical Trial

Conditions
-----------------
Asthma

Intervention / Treatment
-----------------
* Behavioral: High Intensity Interval Training


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Asthma (The diagnose of asthma is based on symptoms and at least one positive asthma test the last 5 years (AHR to either mannitol or methacholine, reversibility to beta2-agonist, peak flow variation or positive eucapnic voluntary hyperventilation test)) ACQ ≥ 1 and ≤ 2.5 On a daily dose of ICS at a minimum of 400 µg budesonide or equivalent ICS for 3 months and with no changes in asthma medicine 4 weeks prior to enrollment Untrained (no participation in vigorous exercise for more than 1 hour per week during the last 2 month) Capable of exercising on bike Exclusion Criteria: Unable to speak and understand Danish Infection within 4 weeks prior to visit 100* Asthma exacerbation within 4 weeks prior to visit 100* Hospitalized for an asthma attack during the last 2 months Treatment with immunotherapy within 5 T½ of the treatment drug prior to visit 100 Initiation of allergen immunotherapy within 3 months prior to visit 100 or plan to begin therapy during study period Treatment with peroral prednisolone Respiratory: other chronic pulmonary disease of clinically significance Cardiovascular: Unstable ischemic heart disease, myocardial infarction within the last 12 months, symptomatic heart failure (NYHA III-IV or EF <40%), symptomatic heart arrhythmia (documented with ECG), uncontrolled hypertension (>155/100) Pregnancy or breastfeeding or planned pregnancy within the next 12 months Other inflammatory or metabolic diseases with the exception of rhinitis, atopy and well-controlled hypothyroidism treated with or without Eltroxin Vaccination less than 2 weeks prior to any visit Current or former smokers with > 20 pack years Subjects, who by investigators determination, will not be able to adhere to study protocol If patients are excluded due to a recent infection or exacerbation they can undergo re-screening after a total of 4 weeks after end of exacerbation treatment/clearing the infection.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: A randomized, controlled parallel group, outcome assessor blinded, clinical trial
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Training group<br>Supervised High intensity interval training (HIIT) 3 times a week for 6 months. Training session: 10 minutes warm up (Low-moderate intensity) 30 minutes intervention (16 minutes HIIT) 10 minutes cool down(Low-moderate intensity) | Behavioral: High Intensity Interval Training<br>* Training (HIIT)<br>* Other names: Training group;|
| No Intervention: Control group<br>Control group, usual lifestyle. Aside from training intervention, all other visits are the same as intervention group (training). | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduced inhaled corticosteroid (ICS) 6 months | The proportion of participants at 6 months that have been down-titrated in ICS dose by at least 25% compared to the participants' baseline dose | 6 months +/- 7 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduced inhaled corticosteroid (ICS) 12 months | The proportion of participants at 12 months that have been down-titrated in ICS dose by at least 25 % compared to baseline. | 12 months +/- 7 days | 
| Cumulated ICS 6 months | Change from baseline in cumulated dose of ICS at 6 months | 6 months +/- 7 days | 
| Cumulated ICS 12 months | Change from baseline in cumulated dose of ICS at 12 months | 12 months +/- 7 days | 
| Cumulated Long acting beta2 agonists (LABA) 6 months | Change from baseline in cumulated dose of LABA at 6 months | 6 months +/- 7 days | 
| Cumulated LABA 12 months | Change from baseline in cumulated dose of LABA at 12 months | 12 months +/- 7 days | 
| Exacerbation rate 6 months | Number of exacerbations (moderate-severe) at 6 months | 6 months +/- 7 days | 
| Exacerbation rate 12 months | Number of exacerbations (moderate-severe) at 12 months | 12 months +/- 7 days | 
| miniAQLQ 6 months | Change from baseline in Asthma life quality evaluated by miniAQLQ at 6 months | 6 months +/- 7 days | 
| miniAQLQ 12 months | Change from baseline in Asthma life quality evaluated by miniAQLQ at 12 months | 12 months +/- 7 days | 
| Fraction of exhaled Nitrogen Oxid 6 months | Change from baseline in Airway inflammation evaluated by FeNO at 6 months | 6 months +/- 7 days | 
| Fraction of exhaled Nitrogen Oxid 12 months | Change from baseline in Airway inflammation evaluated by FeNO at 12 months | 12 months +/- 7 days | 
| Sputum cell count 6 months | Change from baseline in Airway inflammation evaluated by sputum cell count at 6 months | 6 months +/- 7 days | 
| Sputum cell count 12 months | Change from baseline in Airway inflammation evaluated by sputum cell count at 12 months | 12 months +/- 7 days | 
| Systemic inflammation 6 months | Change from baseline in systemic inflammation evaluated by blood eosinophilic, hsCRP and inflammatory cytokines (e.g. IL-6 and IL-8) and TNF-alfa at 6 months | 6 months +/- 7 days | 
| Systemic inflammation 12 months | Change from baseline in systemic inflammation evaluated by blood eosinophilic, hsCRP and inflammatory cytokines (e.g. IL-6 and IL-8) and TNF-alfa at 12 months | 12 months +/- 7 days | 
| Airway hyperresponsiveness | Change from baseline in airway hyperresponsiveness measured by methacholine test at 6 months | 6 months +/- 7 days | 
| FEV1 6 months | Change from baseline in lung function evaluated by FEV1 at 6 months | 6 months +/- 7 days | 
| FVC 6 months | Change from baseline in lung function evaluated by FVC at 6 months | 6 months +/- 7 days | 
| FEV1 12 months | Change from baseline in lung function evaluated by FEV1 at 12 months | 12 months +/- 7 days | 
| FVC 12 months | Change from baseline in lung function evaluated by FVC at 12 months | 12 months +/- 7 days | 
| Cardiopulmonary fitness | Change from baseline in cardiopulmonary fitness evaluated by maximum oxygen consumption at 6 months (VO2max) | 6 months +/- 7 days | 
| Change in fat and muscle composition (DEXA scan) | Change from baseline in fat and muscle composition evaluated by DEXA scan | 6 months +/- 7 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Asthma, Exercise, Asthma treatment, Inhaled corticosteroid, Rehabilitation