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

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

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.

Study Overview

• Status: Completed
• Conditions: Asthma
• Intervention / Treatment: Behavioral: High Intensity Interval Training

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 Type: Interventional
• Enrollment (Actual): 150
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Copenhagen NV, Denmark, 2400
    • Respiratory Research Unit, Birpebjerg Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 71 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Training group; 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; Training (HIIT); Other Names: Training group
No Intervention: Control group; 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Eosinophilic subpopulation - exploratory analyses 6 months	To evaluate the effect of the intervention in sub-populations of asthmatics using different cut-off values of blood eosinophilics. Both regarding primary outcome and secondary outcomes.	6 months +/- 7 days
Eosinophilic subpopulation - exploratory analyses 12 months	To evaluate the effect of the intervention in sub-populations of asthmatics using different cut-off values of blood eosinophilics with regards to secondary outcomes at 12 months.	12 months +/- 7 days

Collaborators and Investigators

• Sponsor: Bispebjerg Hospital
• Investigators: Principal Investigator: Vibeke Backer, professor, Rigshospitalet, Denmark

Study record dates

Study Major Dates

• Study Start (Actual): October 13, 2017
• Primary Completion (Actual): June 26, 2020
• Study Completion (Actual): December 4, 2020

Study Registration Dates

• First Submitted: September 18, 2017
• First Submitted That Met QC Criteria: September 19, 2017
• First Posted (Actual): September 25, 2017

Study Record Updates

• Last Update Posted (Actual): March 15, 2021
• Last Update Submitted That Met QC Criteria: March 11, 2021
• Last Verified: March 1, 2021

More Information

Terms related to this study

• Keywords: Rehabilitation; Exercise; Asthma; Inhaled corticosteroid; Asthma treatment
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma
• Other Study ID Numbers: REPLACE

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