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

Not Applicable

Completed

• Conditions: Asthma
• Interventions: Behavioral: High Intensity Interval Training

• Registration Number: NCT03290898
• Lead Sponsor: Bispebjerg Hospital

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.

Study Timeline

• Study First Submitted: 2017-09-18
• Study First Submitted QC: 2017-09-19
• Study First Posted: 2017-09-25
• Study Start: 2017-10-13
• Primary Completion: 2020-06-26
• Study Completion: 2020-12-04
• Status Verified: 2021-03
• Last Update Submitted: 2021-03-11
• Last Update Posted: 2021-03-15

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Training group	High Intensity Interval Training	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)

Primary Outcome Measures

Name	Time	Method
Reduced inhaled corticosteroid (ICS) 6 months	6 months +/- 7 days	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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Respiratory Research Unit, Birpebjerg Hospital; 🇩🇰 Copenhagen NV, Denmark