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

NCT ID: NCT05215509

Last Updated: 2024-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 69 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-01-01
• Study Completion Date: 2023-12-31

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).

Conditions

Rheumatoid Arthritis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: HEALTH_SERVICES_RESEARCH
• Blinding Strategy: SINGLE

Study Groups

RA patients TNFi Exercise

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

Group Type: EXPERIMENTAL

Exercise

Intervention Type: BEHAVIORAL

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

RA patients TNFi Control

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

Group Type: ACTIVE_COMPARATOR

No exercise

Intervention Type: BEHAVIORAL

Control group, therefore no supervised exercise regime

RA patients IL-6Rb Exercise

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

Group Type: EXPERIMENTAL

Exercise

Intervention Type: BEHAVIORAL

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

RA patients IL-6Rb Control

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

Group Type: ACTIVE_COMPARATOR

No exercise

Intervention Type: BEHAVIORAL

Control group, therefore no supervised exercise regime

Interventions

Exercise

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

Intervention Type: BEHAVIORAL

No exercise

Control group, therefore no supervised exercise regime

Intervention Type: BEHAVIORAL

Other Intervention Names

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Regitse Christensen

Principal investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Regitse Christensen

Role: PRINCIPAL_INVESTIGATOR

Center for Physical Activity Research, Rigshospitalet

Locations

Rigshospitalet

Copenhagen, , Denmark

Countries

Denmark

References

Jonck S, Adamsen ML, Rasmussen IE, Lytzen AA, Lok M, Vonsild Lund MA, Dreyer L, Jorgensen PG, Vejlstrup N, Kober L, Christensen R, Jacobsen S, Pedersen BK, Ellingsgaard H, Hojgaard P, Berg RMG, Christensen RH. IL-6 Inhibitors and TNF Inhibitors: Impact on Exercise-induced Cardiac Adaptations in Patients With Rheumatoid Arthritis. JACC Basic Transl Sci. 2025 May;10(5):551-563. doi: 10.1016/j.jacbts.2024.11.010. Epub 2025 Feb 5.

Reference Type: DERIVED

PMID: 40436519 (View on PubMed)

Jonck S, Adamsen ML, Hojgaard P, Rasmussen IE, Ellingsgaard H, Lund MAV, Jorgensen PG, Jacobsen S, Kober L, Vejlstrup N, Dreyer L, Pedersen BK, Berg RMG, Christensen RH. Effect of a 12-week high-intensity exercise intervention: a comparison of cardiac exercise adaptations during biological disease-modifying antirheumatic drug treatment (TNF inhibitors vs IL-6 signalling inhibitors) in patients with rheumatoid arthritis - study protocol for a randomised controlled trial. BMJ Open. 2023 May 11;13(5):e068600. doi: 10.1136/bmjopen-2022-068600.

Reference Type: DERIVED

PMID: 37169504 (View on PubMed)

Provided Documents

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

H-21010559

Identifier Type: -

Identifier Source: org_study_id