Clinical trial NCT05215509: Exercise-induced Cardiac Adaptions in Rheumatoid Arthritis Patients During IL-6 vs. TNF Antibody Therapy
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
Overall status: COMPLETED
Phase: NA
Conditions: Rheumatoid Arthritis
Keywords: Cardiac adaptations
Metabolic adaptations
High intensity interval training
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
First posted: 2022-01-31
Enrollment: 69
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: HEALTH_SERVICES_RESEARCH

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).

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

Primary outcomes:
measure: Change in left ventricular mass
timeFrame: 12 weeks
Secondary outcomes:
measure: Visceral adipose tissue mass
timeFrame: 12 weeks
measure: Stroke volume
timeFrame: 12 weeks
measure: Left ventricular and atrial end-diastolic volume
timeFrame: 12 weeks
measure: LVEF
timeFrame: 12 weeks
measure: Global longitudinal strain
timeFrame: 12 weeks
measure: E/A ratio
timeFrame: 12 weeks
measure: E/é
timeFrame: 12 weeks
measure: Left ventricular and atrial end-systolic volume
timeFrame: 12 weeks
measure: Left atrial volume index
timeFrame: 12 weeks
measure: Interventricular septum thickness
timeFrame: 12 weeks
measure: Left ventricular posterior wall thickness
timeFrame: 12 weeks
measure: Aortic and pulmonary distensibility and pulse wave velocity
timeFrame: 12 weeks
measure: Subcutaneous, visceral and epicardial adipose tissue
timeFrame: 12 weeks
measure: Intramyocardial triglyceride content
timeFrame: 12 weeks
measure: Cardiorespiratory fitness
timeFrame: 12 weeks
measure: Dynamic spirometry
timeFrame: 12 weeks
measure: Whole body plethysmography
timeFrame: 12 weeks
measure: Diffusion capacity
timeFrame: 12 weeks
measure: Body composition
timeFrame: 12 weeks
measure: Oral glucose tolerance test
timeFrame: 12 weeks
measure: Axial accelerometer-based physical activity monitors
timeFrame: 5 days in week 6 of the intervention/control
measure: Dietary intake
timeFrame: 3 days in the week 6 of intervention/control
measure: Blood sample
timeFrame: 12 weeks
measure: Blood sample
timeFrame: 12 weeks
measure: RA disease specific outcomes 1
timeFrame: 12 weeks
measure: RA disease specific outcomes 2
timeFrame: 12 weeks
measure: RA disease specific outcomes 3
timeFrame: 12 weeks
measure: RA disease specific outcomes 4
timeFrame: 12 weeks
measure: RA disease specific outcomes 5
timeFrame: 12 weeks
measure: RA disease specific outcomes 6
timeFrame: 12 weeks
measure: RA disease specific outcomes 7
timeFrame: 12 weeks
measure: RA disease specific outcomes 8
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
Study officials:
affiliation: Center for Physical Activity Research, Rigshospitalet
name: Regitse Christensen
role: PRINCIPAL_INVESTIGATOR
References: