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Completed

NCT Number: NCT05215509

Exercise-induced Cardiac Adaptions in Rheumatoid Arthritis Patients During IL-6 vs. TNF Antibody Therapy

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.

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Key information

Conditions

Rheumatoid Arthritis Arthritis Arthritis, Rheumatoid Autoimmune Diseases Connective Tissue Diseases Immune System Diseases Joint Diseases Musculoskeletal Diseases Rheumatic Diseases Skin and Connective Tissue Diseases

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Rigshospitalet

Copenhagen, 2100, Denmark

About this study

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).

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Exercise

Behavioral

Supervised high-intensity interval training for 12 weeks three times per week. The supervision may be physical or online supervision

Other names: High intensity interval training

No exercise

Behavioral

Control group, therefore no supervised exercise regime

Primary outcomes

  1. Change in left ventricular mass

    Time frame: 12 weeks

    measured by MRI scan

Secondary outcomes

  1. Visceral adipose tissue mass

    Time frame: 12 weeks

    measured by MRI scan

  2. Stroke volume

    Time frame: 12 weeks

    Structural cardiac parameter: measured by MRI scan and echocardiography

  3. Left ventricular and atrial end-diastolic volume

    Time frame: 12 weeks

    Structural cardiac parameter: measured by MRI scan and echocardiography

  4. LVEF

    Time frame: 12 weeks

    Functional cardiac parameters: measured by MRI scan and echocardiography

  5. Global longitudinal strain

    Time frame: 12 weeks

    Functional cardiac parameters: measured by MRI scan and echocardiography

  6. E/A ratio

    Time frame: 12 weeks

    Functional cardiac parameters: measured by MRI scan and echocardiography

  7. E/é

    Time frame: 12 weeks

    Functional cardiac parameters: measured by MRI scan and echocardiography

  8. Left ventricular and atrial end-systolic volume

    Time frame: 12 weeks

    Structural cardiac parameter: measured by MRI scan and echocardiography

  9. Left atrial volume index

    Time frame: 12 weeks

    Structural cardiac parameter: measured by MRI scan and echocardiography

  10. Interventricular septum thickness

    Time frame: 12 weeks

    Structural cardiac parameter: measured by MRI scan and echocardiography

  11. Left ventricular posterior wall thickness

    Time frame: 12 weeks

    Structural cardiac parameter: measured by MRI scan and echocardiography

  12. Aortic and pulmonary distensibility and pulse wave velocity

    Time frame: 12 weeks

    Functional vascular parameter: measured by MRI

  13. Subcutaneous, visceral and epicardial adipose tissue

    Time frame: 12 weeks

    Measured by MRI and MR spectroscopy

  14. Intramyocardial triglyceride content

    Time frame: 12 weeks

    Measured by MRI and MR spectroscopy

  15. Cardiorespiratory fitness

    Time frame: 12 weeks

    Measured with an incremental VO2 protocol on exercise bike

  16. Dynamic spirometry

    Time frame: 12 weeks

    Pulmonary function testing

  17. Whole body plethysmography

    Time frame: 12 weeks

    Pulmonary function testing

  18. Diffusion capacity

    Time frame: 12 weeks

    Pulmonary function testing

  19. Body composition

    Time frame: 12 weeks

    Measured by a DXA scan

  20. Oral glucose tolerance test

    Time frame: 12 weeks

    75g of glucose taken while fasting

  21. Axial accelerometer-based physical activity monitors

    Time frame: 5 days in week 6 of the intervention/control

    Free-living physical activity is measured using axial accelerometer-based physical activity monitors (AX3; Axivity, Newcastle upon Tyne, UK) for a 5-day period

  22. Dietary intake

    Time frame: 3 days in the week 6 of intervention/control

    Self reported intake of all foods and liquids

  23. Blood sample

    Time frame: 12 weeks

    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.

  24. Blood sample

    Time frame: 12 weeks

    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.

  25. RA disease specific outcomes 1

    Time frame: 12 weeks

    Change in measures of the international Core Outcome Set for rheumatoid arthritis : 66/68 tender and swollen joint count

  26. RA disease specific outcomes 2

    Time frame: 12 weeks

    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)

  27. RA disease specific outcomes 3

    Time frame: 12 weeks

    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.

  28. RA disease specific outcomes 4

    Time frame: 12 weeks

    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.

  29. RA disease specific outcomes 5

    Time frame: 12 weeks

    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

  30. RA disease specific outcomes 6

    Time frame: 12 weeks

    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

  31. RA disease specific outcomes 7

    Time frame: 12 weeks

    Change in response criteria will be assessed according the American College of Rheumatology (ACR 20/50/70) response

  32. RA disease specific outcomes 8

    Time frame: 12 weeks

    Change in response criteria will be assessed according the European League Against Rheumatism (EULAR none/good/moderate response)

Sponsors and collaborators

Lead sponsor

Rigshospitalet, Denmark

Other

Registry information

Official study title

Exercise-induced Cardiac Adaptions in Rheumatoid Arthritis Patients During Interleukin-6 vs. Tumor Necrosis Factor Antibody Therapy: a Randomised, Controlled Study.

Acronym: RABEX

Important dates

Study start
2021
Primary completion
2023
Study completion
2023
First posted
Jan 31, 2022
Registry last updated
Feb 2, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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