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

Primary Purpose

Asthma

Status

Completed

Phase

Not Applicable

Locations

Denmark

Study Type

Interventional

Intervention

High Intensity Interval Training

About this trial

This is an interventional treatment trial for Asthma focused on measuring Asthma, Exercise, Asthma treatment, Inhaled corticosteroid, Rehabilitation

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

Respiratory Research Unit, Birpebjerg Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

No Intervention

Arm Label

Training group

Control group

Arm Description

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)

Control group, usual lifestyle. Aside from training intervention, all other visits are the same as intervention group (training).

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.

Cumulated ICS 6 months

Change from baseline in cumulated dose of ICS at 6 months

Cumulated ICS 12 months

Change from baseline in cumulated dose of ICS at 12 months

Cumulated Long acting beta2 agonists (LABA) 6 months

Change from baseline in cumulated dose of LABA at 6 months

Cumulated LABA 12 months

Change from baseline in cumulated dose of LABA at 12 months

Exacerbation rate 6 months

Number of exacerbations (moderate-severe) at 6 months

Exacerbation rate 12 months

Number of exacerbations (moderate-severe) at 12 months

miniAQLQ 6 months

Change from baseline in Asthma life quality evaluated by miniAQLQ at 6 months

miniAQLQ 12 months

Change from baseline in Asthma life quality evaluated by miniAQLQ at 12 months

Fraction of exhaled Nitrogen Oxid 6 months

Change from baseline in Airway inflammation evaluated by FeNO at 6 months

Fraction of exhaled Nitrogen Oxid 12 months

Change from baseline in Airway inflammation evaluated by FeNO at 12 months

Sputum cell count 6 months

Change from baseline in Airway inflammation evaluated by sputum cell count at 6 months

Sputum cell count 12 months

Change from baseline in Airway inflammation evaluated by sputum cell count at 12 months

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

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

Airway hyperresponsiveness

Change from baseline in airway hyperresponsiveness measured by methacholine test at 6 months

FEV1 6 months

Change from baseline in lung function evaluated by FEV1 at 6 months

FVC 6 months

Change from baseline in lung function evaluated by FVC at 6 months

FEV1 12 months

Change from baseline in lung function evaluated by FEV1 at 12 months

FVC 12 months

Change from baseline in lung function evaluated by FVC at 12 months

Cardiopulmonary fitness

Change from baseline in cardiopulmonary fitness evaluated by maximum oxygen consumption at 6 months (VO2max)

Change in fat and muscle composition (DEXA scan)

Change from baseline in fat and muscle composition evaluated by DEXA scan

Full Information

NCT ID

NCT03290898

First Posted

September 18, 2017

Last Updated

March 11, 2021

Sponsor

Bispebjerg Hospital

1. Study Identification

Unique Protocol Identification Number

NCT03290898

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

March 2021

Overall Recruitment Status

Completed

Study Start Date

October 13, 2017 (Actual)

Primary Completion Date

June 26, 2020 (Actual)

Study Completion Date

December 4, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Principal Investigator

Name of the Sponsor

Bispebjerg Hospital

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Asthma

Keywords

Asthma, Exercise, Asthma treatment, Inhaled corticosteroid, Rehabilitation

7. Study Design

Primary Purpose

Treatment

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Model Description

A randomized, controlled parallel group, outcome assessor blinded, clinical trial

Masking

InvestigatorOutcomes Assessor

Masking Description

Single blindet, randomization and training intervention by non-investigator. Open-label after primary follow up. After unblinding, blindet 3rd party performs tests (visit 9 and 12 months, e.g. spirometry)

Allocation

Randomized

Enrollment

150 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Training group

Arm Type

Active Comparator

Arm Description

Arm Title

Control group

Arm Type

No Intervention

Arm Description

Control group, usual lifestyle. Aside from training intervention, all other visits are the same as intervention group (training).

Intervention Type

Behavioral

Intervention Name(s)

High Intensity Interval Training

Other Intervention Name(s)

Training group

Intervention Description

Training (HIIT)

Primary Outcome Measure Information:

Title

Reduced inhaled corticosteroid (ICS) 6 months

Description

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

Time Frame

6 months +/- 7 days

Secondary Outcome Measure Information:

Title

Reduced inhaled corticosteroid (ICS) 12 months

Description

The proportion of participants at 12 months that have been down-titrated in ICS dose by at least 25 % compared to baseline.

Time Frame

12 months +/- 7 days

Title

Cumulated ICS 6 months

Description

Change from baseline in cumulated dose of ICS at 6 months

Time Frame

6 months +/- 7 days

Title

Cumulated ICS 12 months

Description

Change from baseline in cumulated dose of ICS at 12 months

Time Frame

12 months +/- 7 days

Title

Cumulated Long acting beta2 agonists (LABA) 6 months

Description

Change from baseline in cumulated dose of LABA at 6 months

Time Frame

6 months +/- 7 days

Title

Cumulated LABA 12 months

Description

Change from baseline in cumulated dose of LABA at 12 months

Time Frame

12 months +/- 7 days

Title

Exacerbation rate 6 months

Description

Number of exacerbations (moderate-severe) at 6 months

Time Frame

6 months +/- 7 days

Title

Exacerbation rate 12 months

Description

Number of exacerbations (moderate-severe) at 12 months

Time Frame

12 months +/- 7 days

Title

miniAQLQ 6 months

Description

Change from baseline in Asthma life quality evaluated by miniAQLQ at 6 months

Time Frame

6 months +/- 7 days

Title

miniAQLQ 12 months

Description

Change from baseline in Asthma life quality evaluated by miniAQLQ at 12 months

Time Frame

12 months +/- 7 days

Title

Fraction of exhaled Nitrogen Oxid 6 months

Description

Change from baseline in Airway inflammation evaluated by FeNO at 6 months

Time Frame

6 months +/- 7 days

Title

Fraction of exhaled Nitrogen Oxid 12 months

Description

Change from baseline in Airway inflammation evaluated by FeNO at 12 months

Time Frame

12 months +/- 7 days

Title

Sputum cell count 6 months

Description

Change from baseline in Airway inflammation evaluated by sputum cell count at 6 months

Time Frame

6 months +/- 7 days

Title

Sputum cell count 12 months

Description

Change from baseline in Airway inflammation evaluated by sputum cell count at 12 months

Time Frame

12 months +/- 7 days

Title

Systemic inflammation 6 months

Description

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

Time Frame

6 months +/- 7 days

Title

Systemic inflammation 12 months

Description

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

Time Frame

12 months +/- 7 days

Title

Airway hyperresponsiveness

Description

Change from baseline in airway hyperresponsiveness measured by methacholine test at 6 months

Time Frame

6 months +/- 7 days

Title

FEV1 6 months

Description

Change from baseline in lung function evaluated by FEV1 at 6 months

Time Frame

6 months +/- 7 days

Title

FVC 6 months

Description

Change from baseline in lung function evaluated by FVC at 6 months

Time Frame

6 months +/- 7 days

Title

FEV1 12 months

Description

Change from baseline in lung function evaluated by FEV1 at 12 months

Time Frame

12 months +/- 7 days

Title

FVC 12 months

Description

Change from baseline in lung function evaluated by FVC at 12 months

Time Frame

12 months +/- 7 days

Title

Cardiopulmonary fitness

Description

Change from baseline in cardiopulmonary fitness evaluated by maximum oxygen consumption at 6 months (VO2max)

Time Frame

6 months +/- 7 days

Title

Change in fat and muscle composition (DEXA scan)

Description

Change from baseline in fat and muscle composition evaluated by DEXA scan

Time Frame

6 months +/- 7 days

Other Pre-specified Outcome Measures:

Title

Eosinophilic subpopulation - exploratory analyses 6 months

Description

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.

Time Frame

6 months +/- 7 days

Title

Eosinophilic subpopulation - exploratory analyses 12 months

Description

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.

Time Frame

12 months +/- 7 days

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

75 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Vibeke Backer, professor

Organizational Affiliation

Rigshospitalet, Denmark

Official's Role

Principal Investigator

Facility Information:

Facility Name

Respiratory Research Unit, Birpebjerg Hospital

City

Copenhagen NV

ZIP/Postal Code

2400

Country

Denmark

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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