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

Rigshospitalet

Status: Completed

Conditions: Rheumatoid Arthritis

Treatments: Behavioral: No exercise; Behavioral: Exercise

Study type: Interventional

Funder types: Other

Identifiers

NCT05215509

H-21010559

Details and patient eligibility

About

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.

Full 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).

Enrollment: 69 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Health Services Research

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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69 participants in 4 patient groups

RA patients TNFi Exercise

Experimental group

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

Treatment:

Behavioral: Exercise

RA patients TNFi Control

Active Comparator group

Description:

This group will be allocated to "control" and therefore no supervised exercise regimen

Treatment:

Behavioral: No exercise

RA patients IL-6Rb Exercise

Experimental group

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

Treatment:

Behavioral: Exercise

RA patients IL-6Rb Control

Active Comparator group

Description:

This group will be allocated to "control" and therefore no supervised exercise regimen

Treatment:

Behavioral: No exercise