Back to resultsExercise-induced Cardiac Adaptions in Rheumatoid Arthritis Patients During Interleukin-6 vs. Tumor Necrosis Factor Antibody Therapy (RABEX)
Primary Purpose
Rheumatoid Arthritis
Status
Recruiting
Phase
Not Applicable
Locations
Denmark
Study Type
Interventional
Intervention
Exercise
No exercise
Sponsored by
About this trial
This is an interventional health services research trial for Rheumatoid Arthritis focused on measuring Cardiac adaptations, Metabolic adaptations, High intensity interval training
Eligibility Criteria
Inclusion Criteria:
- Age >= 18 and <70 years
- Informed consent
- Diagnosed RA based on the 2010 American College of Rheumatology/ EULAR criteria. In biological treatment with either IL-6rB og TNFi over four months prior to enrollment
- Low RA disease activity, based on the Disease Activity Score-28 ESR for Rheumatoid Arthritis (DAS28) <=3.2
- An electrocardiogram without features of left ventricular hypertrophy defined by the European Society of Cardiology
Females of childbearing potential have to use one or more of the following highly effective methods for contraception in order to be included:
- Vasectomized partner
- Bilateral tubal occlusion
- Sexual abstinence
- Intrauterine device
- Hormonal contraception
Females who are considered to have no childbearing potential are
- Bilateral tubal ligation
- Bilateral oophorectomy
- Complete hysterectomy
- Postmenopausal defined as 12 months with no menses without an alternative medical cause
Exclusion Criteria:
- Health conditions that prevent participating in the exercise intervention determined by the Project Coordinator
- Subjects who cannot undergo MRI scans (metallic implants or claustrophobia)
- Corticosteroid use per os > 10 mg/day within seven days of study enrollment
- Intramuscular corticosteroid within 3 weeks of the study enrollment
- Grade 2 hypertension (systolic BP > 160 mmHg and/or diastolic BP >100 mmHg) despite the use of antihypertensive drugs.
- Pregnancy
- Subjects with insulin dependent Diabetes
Sites / Locations
- RigshospitaletRecruiting
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm 4
Arm Type
Experimental
Active Comparator
Experimental
Active Comparator
Arm Label
RA patients TNFi Exercise
RA patients TNFi Control
RA patients IL-6Rb Exercise
RA patients IL-6Rb Control
Arm Description
The patients will be randomized to 12-week supervised exercise training intervention or no exercise training. The exercise training program includes three supervised sessions per week over a 12-week period. The program consists of high intensity endurance training on ergometer bicycles. The intensity will progress throughout the 12 weeks of training. The training consists of 10 minutes of warm up at 40-60% maximum heart rate (HRmax), followed by 25 minutes of high intensity interval training (4 bouts of 4 min at >85% HRmax interspaced by 3 minutes of low intensity training at 40-60% Hrmax) and finally a 5 min cool-down of 50% Hrmax
This group will be allocated to "control" and therefore no supervised exercise regimen
The patients will be randomized to 12-week supervised exercise training intervention or no exercise training. The exercise training program includes three supervised sessions per week over a 12-week period. The program consists of high intensity endurance training on ergometer bicycles. The intensity will progress throughout the 12 weeks of training. The training consists of 10 minutes of warm up at 40-60% maximum heart rate (HRmax), followed by 25 minutes of high intensity interval training (4 bouts of 4 min at >85% HRmax interspaced by 3 minutes of low intensity training at 40-60% Hrmax) and finally a 5 min cool-down of 50% Hrmax
This group will be allocated to "control" and therefore no supervised exercise regimen
Outcomes
Primary Outcome Measures
Change in left ventricular mass
measured by MRI scan
Secondary Outcome Measures
Visceral adipose tissue mass
measured by MRI scan
Stroke volume
Structural cardiac parameter: measured by MRI scan and echocardiography
Left ventricular and atrial end-diastolic volume
Structural cardiac parameter: measured by MRI scan and echocardiography
LVEF
Functional cardiac parameters: measured by MRI scan and echocardiography
Global longitudinal strain
Functional cardiac parameters: measured by MRI scan and echocardiography
E/A ratio
Functional cardiac parameters: measured by MRI scan and echocardiography
E/é
Functional cardiac parameters: measured by MRI scan and echocardiography
Left ventricular and atrial end-systolic volume
Structural cardiac parameter: measured by MRI scan and echocardiography
Left atrial volume index
Structural cardiac parameter: measured by MRI scan and echocardiography
Interventricular septum thickness
Structural cardiac parameter: measured by MRI scan and echocardiography
Left ventricular posterior wall thickness
Structural cardiac parameter: measured by MRI scan and echocardiography
Aortic and pulmonary distensibility and pulse wave velocity
Functional vascular parameter: measured by MRI
Subcutaneous, visceral and epicardial adipose tissue
Measured by MRI and MR spectroscopy
Intramyocardial triglyceride content
Measured by MRI and MR spectroscopy
Cardiorespiratory fitness
Measured with an incremental VO2 protocol on exercise bike
Dynamic spirometry
Pulmonary function testing
Whole body plethysmography
Pulmonary function testing
Diffusion capacity
Pulmonary function testing
Body composition
Measured by a DXA scan
Oral glucose tolerance test
75g of glucose taken while fasting
Axial accelerometer-based physical activity monitors
Free-living physical activity is measured using axial accelerometer-based physical activity monitors (AX3; Axivity, Newcastle upon Tyne, UK) for a 5-day period
Dietary intake
Self reported intake of all foods and liquids
Blood sample
Change in fasting total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol (mmol/L). Following an overnight fast (10 hours), blood samples are collected and processed by a trained laboratory technician and analysed according to standard procedures.
Blood sample
Change in triglycerides (mmol/L). Following an overnight fast (10 hours), blood samples are collected and processed by a trained laboratory technician and analysed according to standard procedures.
RA disease specific outcomes 1
Change in measures of the international Core Outcome Set for rheumatoid arthritis : 66/68 tender and swollen joint count
RA disease specific outcomes 2
Change in visual analogue scale (VAS) pain, VAS physician global assessment, VAS patient global assessment
The Visual Analogue Scale (VAS) is a self-report measure consisting simply of a 100 mm horixontal line with a statement at each end representing one extreme (0mm = nothing, 100mm = extreme)
RA disease specific outcomes 3
Change in Health Assessment Questionnaire (HAQ-DI)
Total score is between 0-3.0. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment.
RA disease specific outcomes 4
Change in Short Form 36 (SF-36) Health Survey Questionnaire
A 8-scale score within 8 domains.All items are scored so that a high score defines a more favorable health state.
RA disease specific outcomes 5
Change in the composite Disease Activity Score-28 ESR for Rheumatoid Arthritis (DAS28).
A DAS28 of greater than 5.1 implies active disease, less than 3.2 low disease activity, and less than 2.6 remission
RA disease specific outcomes 6
Change in response criteria will be assessed according the clinical disease activity index (CDAI).
The CDAI composite index quantifies disease activity in RA, by utilising four clinical parameters including tender and swollen joints and global assessment from both patient and assessor on a vasual analogue scale.
CDAI interpretation score CDAI ≥ 22,1: High Activity CDAI < 22,1 og ≥10,1: Moderate Activity CDAI <10,0 og ≥ 2,9: Low Activity CDAI <2,9: Remission
RA disease specific outcomes 7
Change in response criteria will be assessed according the American College of Rheumatology (ACR 20/50/70) response
RA disease specific outcomes 8
Change in response criteria will be assessed according the European League Against Rheumatism (EULAR none/good/moderate response)
Full Information
NCT ID
NCT05215509
First Posted
November 16, 2021
Last Updated
April 2, 2023
Sponsor
Rigshospitalet, Denmark
1. Study Identification
Unique Protocol Identification Number
NCT05215509
Brief Title
Exercise-induced Cardiac Adaptions in Rheumatoid Arthritis Patients During Interleukin-6 vs. Tumor Necrosis Factor Antibody Therapy
Acronym
RABEX
Official Title
Exercise-induced Cardiac Adaptions in Rheumatoid Arthritis Patients During Interleukin-6 vs. Tumor Necrosis Factor Antibody Therapy: a Randomised, Controlled Study.
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Recruiting
Study Start Date
December 1, 2021 (Actual)
Primary Completion Date
December 31, 2023 (Anticipated)
Study Completion Date
March 30, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Rigshospitalet, Denmark
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The present study will investigative the physiological effects of the cytokines interleukin-6 (IL-6) and tumor necrosis factor (TNF) on the adaptive changes to exercise in patients with rheumatoid arthritis. The investigators hypothesize that blockage of IL-6 receptors will decrease the cardiac and metabolic adaptations to exercise training compared to the inhibition of TNF. 80 patients will be included in a 12-week investigator blinded randomised exercise training intervention study.
Detailed Description
80 patients with rheumatoid arthritis who are being treated with either interleukin-6 receptor blockers (IL-6Rb) or tumor necrosis factor inhibitors (TNFi) for a minimum of four months prior to enrollment will be recruited and undergo baseline testing, including examination, biochemistry, ECG, DXA, OGTT, pulmonary function, VO2max, echocardiography, cardiac MRI.
After baseline testing, 40 patients in IL-6 receptor blocker treatment and 40 patients in TNF inhibitor treatment.will be randomly allocated into one group receiving standard of care (control group) or a group performing supervised high-intensity interval training three times a week over a period of 12 weeks. The randomization procedure involves a computer-generated block randomization schedule in a ratio of 1:1 stratified by sex by an independent person. Following the 12-week intervention period, all groups will complete a series of follow-up tests (as baseline testing).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rheumatoid Arthritis
Keywords
Cardiac adaptations, Metabolic adaptations, High intensity interval training
7. Study Design
Primary Purpose
Health Services Research
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Investigator
Allocation
Randomized
Enrollment
80 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
RA patients TNFi Exercise
Arm Type
Experimental
Arm Description
The patients will be randomized to 12-week supervised exercise training intervention or no exercise training. The exercise training program includes three supervised sessions per week over a 12-week period.
The program consists of high intensity endurance training on ergometer bicycles. The intensity will progress throughout the 12 weeks of training. The training consists of 10 minutes of warm up at 40-60% maximum heart rate (HRmax), followed by 25 minutes of high intensity interval training (4 bouts of 4 min at >85% HRmax interspaced by 3 minutes of low intensity training at 40-60% Hrmax) and finally a 5 min cool-down of 50% Hrmax
Arm Title
RA patients TNFi Control
Arm Type
Active Comparator
Arm Description
This group will be allocated to "control" and therefore no supervised exercise regimen
Arm Title
RA patients IL-6Rb Exercise
Arm Type
Experimental
Arm Description
The patients will be randomized to 12-week supervised exercise training intervention or no exercise training. The exercise training program includes three supervised sessions per week over a 12-week period.
The program consists of high intensity endurance training on ergometer bicycles. The intensity will progress throughout the 12 weeks of training. The training consists of 10 minutes of warm up at 40-60% maximum heart rate (HRmax), followed by 25 minutes of high intensity interval training (4 bouts of 4 min at >85% HRmax interspaced by 3 minutes of low intensity training at 40-60% Hrmax) and finally a 5 min cool-down of 50% Hrmax
Arm Title
RA patients IL-6Rb Control
Arm Type
Active Comparator
Arm Description
This group will be allocated to "control" and therefore no supervised exercise regimen
Intervention Type
Behavioral
Intervention Name(s)
Exercise
Other Intervention Name(s)
High intensity interval training
Intervention Description
Supervised high-intensity interval training for 12 weeks three times per week. The supervision may be physical or online supervision
Intervention Type
Behavioral
Intervention Name(s)
No exercise
Intervention Description
Control group, therefore no supervised exercise regime
Primary Outcome Measure Information:
Title
Change in left ventricular mass
Description
measured by MRI scan
Time Frame
12 weeks
Secondary Outcome Measure Information:
Title
Visceral adipose tissue mass
Description
measured by MRI scan
Time Frame
12 weeks
Title
Stroke volume
Description
Structural cardiac parameter: measured by MRI scan and echocardiography
Time Frame
12 weeks
Title
Left ventricular and atrial end-diastolic volume
Description
Structural cardiac parameter: measured by MRI scan and echocardiography
Time Frame
12 weeks
Title
LVEF
Description
Functional cardiac parameters: measured by MRI scan and echocardiography
Time Frame
12 weeks
Title
Global longitudinal strain
Description
Functional cardiac parameters: measured by MRI scan and echocardiography
Time Frame
12 weeks
Title
E/A ratio
Description
Functional cardiac parameters: measured by MRI scan and echocardiography
Time Frame
12 weeks
Title
E/é
Description
Functional cardiac parameters: measured by MRI scan and echocardiography
Time Frame
12 weeks
Title
Left ventricular and atrial end-systolic volume
Description
Structural cardiac parameter: measured by MRI scan and echocardiography
Time Frame
12 weeks
Title
Left atrial volume index
Description
Structural cardiac parameter: measured by MRI scan and echocardiography
Time Frame
12 weeks
Title
Interventricular septum thickness
Description
Structural cardiac parameter: measured by MRI scan and echocardiography
Time Frame
12 weeks
Title
Left ventricular posterior wall thickness
Description
Structural cardiac parameter: measured by MRI scan and echocardiography
Time Frame
12 weeks
Title
Aortic and pulmonary distensibility and pulse wave velocity
Description
Functional vascular parameter: measured by MRI
Time Frame
12 weeks
Title
Subcutaneous, visceral and epicardial adipose tissue
Description
Measured by MRI and MR spectroscopy
Time Frame
12 weeks
Title
Intramyocardial triglyceride content
Description
Measured by MRI and MR spectroscopy
Time Frame
12 weeks
Title
Cardiorespiratory fitness
Description
Measured with an incremental VO2 protocol on exercise bike
Time Frame
12 weeks
Title
Dynamic spirometry
Description
Pulmonary function testing
Time Frame
12 weeks
Title
Whole body plethysmography
Description
Pulmonary function testing
Time Frame
12 weeks
Title
Diffusion capacity
Description
Pulmonary function testing
Time Frame
12 weeks
Title
Body composition
Description
Measured by a DXA scan
Time Frame
12 weeks
Title
Oral glucose tolerance test
Description
75g of glucose taken while fasting
Time Frame
12 weeks
Title
Axial accelerometer-based physical activity monitors
Description
Free-living physical activity is measured using axial accelerometer-based physical activity monitors (AX3; Axivity, Newcastle upon Tyne, UK) for a 5-day period
Time Frame
5 days in week 6 of the intervention/control
Title
Dietary intake
Description
Self reported intake of all foods and liquids
Time Frame
3 days in the week 6 of intervention/control
Title
Blood sample
Description
Change in fasting total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol (mmol/L). Following an overnight fast (10 hours), blood samples are collected and processed by a trained laboratory technician and analysed according to standard procedures.
Time Frame
12 weeks
Title
Blood sample
Description
Change in triglycerides (mmol/L). Following an overnight fast (10 hours), blood samples are collected and processed by a trained laboratory technician and analysed according to standard procedures.
Time Frame
12 weeks
Title
RA disease specific outcomes 1
Description
Change in measures of the international Core Outcome Set for rheumatoid arthritis : 66/68 tender and swollen joint count
Time Frame
12 weeks
Title
RA disease specific outcomes 2
Description
Change in visual analogue scale (VAS) pain, VAS physician global assessment, VAS patient global assessment
The Visual Analogue Scale (VAS) is a self-report measure consisting simply of a 100 mm horixontal line with a statement at each end representing one extreme (0mm = nothing, 100mm = extreme)
Time Frame
12 weeks
Title
RA disease specific outcomes 3
Description
Change in Health Assessment Questionnaire (HAQ-DI)
Total score is between 0-3.0. Increasing scores indicate worse functioning with 0 indicating no functional impairment and 3 indicating complete impairment.
Time Frame
12 weeks
Title
RA disease specific outcomes 4
Description
Change in Short Form 36 (SF-36) Health Survey Questionnaire
A 8-scale score within 8 domains.All items are scored so that a high score defines a more favorable health state.
Time Frame
12 weeks
Title
RA disease specific outcomes 5
Description
Change in the composite Disease Activity Score-28 ESR for Rheumatoid Arthritis (DAS28).
A DAS28 of greater than 5.1 implies active disease, less than 3.2 low disease activity, and less than 2.6 remission
Time Frame
12 weeks
Title
RA disease specific outcomes 6
Description
Change in response criteria will be assessed according the clinical disease activity index (CDAI).
The CDAI composite index quantifies disease activity in RA, by utilising four clinical parameters including tender and swollen joints and global assessment from both patient and assessor on a vasual analogue scale.
CDAI interpretation score CDAI ≥ 22,1: High Activity CDAI < 22,1 og ≥10,1: Moderate Activity CDAI <10,0 og ≥ 2,9: Low Activity CDAI <2,9: Remission
Time Frame
12 weeks
Title
RA disease specific outcomes 7
Description
Change in response criteria will be assessed according the American College of Rheumatology (ACR 20/50/70) response
Time Frame
12 weeks
Title
RA disease specific outcomes 8
Description
Change in response criteria will be assessed according the European League Against Rheumatism (EULAR none/good/moderate response)
Time Frame
12 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Age >= 18 and <70 years
Informed consent
Diagnosed RA based on the 2010 American College of Rheumatology/ EULAR criteria. In biological treatment with either IL-6rB og TNFi over four months prior to enrollment
Low RA disease activity, based on the Disease Activity Score-28 ESR for Rheumatoid Arthritis (DAS28) <=3.2
An electrocardiogram without features of left ventricular hypertrophy defined by the European Society of Cardiology
Females of childbearing potential have to use one or more of the following highly effective methods for contraception in order to be included:
Vasectomized partner
Bilateral tubal occlusion
Sexual abstinence
Intrauterine device
Hormonal contraception
Females who are considered to have no childbearing potential are
Bilateral tubal ligation
Bilateral oophorectomy
Complete hysterectomy
Postmenopausal defined as 12 months with no menses without an alternative medical cause
Exclusion Criteria:
Health conditions that prevent participating in the exercise intervention determined by the Project Coordinator
Subjects who cannot undergo MRI scans (metallic implants or claustrophobia)
Corticosteroid use per os > 10 mg/day within seven days of study enrollment
Intramuscular corticosteroid within 3 weeks of the study enrollment
Grade 2 hypertension (systolic BP > 160 mmHg and/or diastolic BP >100 mmHg) despite the use of antihypertensive drugs.
Pregnancy
Subjects with insulin dependent Diabetes
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Regitse Christensen
Phone
0045 23714598
Ext
MD, PhD
Email
regitse.hoejgaard.christensen@regionh.dk
First Name & Middle Initial & Last Name or Official Title & Degree
Ronan Berg
Ext
DMSc, MD
Email
ronan.martin.griffin.berg@regionh.dk
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Regitse Christensen
Organizational Affiliation
Center for Physical Activity Research, Rigshospitalet
Official's Role
Principal Investigator
Facility Information:
Facility Name
Rigshospitalet
City
Copenhagen
ZIP/Postal Code
2100
Country
Denmark
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Regitse Christensen, MD PhD
Phone
23714598
Ext
45
Email
regitse.hoejgaard.christensen@regionh.dk
First Name & Middle Initial & Last Name & Degree
Ronan Berg, DMSc
Email
ronan.martin.griffin.berg@regionh.dk
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Anonymised IPD obtained through this study may be provided to qualified researchers upon reasonable request.
IPD Sharing Time Frame
Requests can be submitted following the publication of the primary outcome, and IPD will be accessible upon reasonable request up to 3 years from that date.
IPD Sharing Access Criteria
Requests to acces IPD may be provided if a satisfactory research proposal is sent to Simon Jønck (simon.joenck.04@regionh.dk) and Regitse H Christensen (regitse.hoejgaard.Christensen@regionh.dk)
Learn more about this trial
Exercise-induced Cardiac Adaptions in Rheumatoid Arthritis Patients During Interleukin-6 vs. Tumor Necrosis Factor Antibody Therapy
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