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

NCT05215509 | Completed DMC

• 1 other identifier: H-21010559
• Study Type: interventional
• Target: 69
• Locations: 1 country
• Sites: 1

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.

Conditions

Rheumatoid Arthritis

Keywords

Cardiac adaptations; Metabolic adaptations; High intensity interval training

Outcome Measures

Primary Outcomes (1)

• Change in left ventricular mass

  measured by MRI scan

  12 weeks

Secondary Outcomes (32)

• Visceral adipose tissue mass

  12 weeks

• Stroke volume

  12 weeks

• Left ventricular and atrial end-diastolic volume

  12 weeks

• LVEF

  12 weeks

• Global longitudinal strain

  12 weeks

Study Arms (4)

RA patients TNFi Exercise

EXPERIMENTAL

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

Behavioral: Exercise

RA patients TNFi Control

ACTIVE COMPARATOR

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

Behavioral: No exercise

RA patients IL-6Rb Exercise

EXPERIMENTAL

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

Behavioral: Exercise

RA patients IL-6Rb Control

ACTIVE COMPARATOR

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

Behavioral: No exercise

Interventions

Exercise BEHAVIORAL

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

Also known as: High intensity interval training

RA patients IL-6Rb Exercise; RA patients TNFi Exercise

No exercise BEHAVIORAL

Control group, therefore no supervised exercise regime

RA patients IL-6Rb Control; RA patients TNFi Control

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead

Study Sites (1)

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Related Publications (2)

• 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.

  PMID: 40436519 DERIVED

• 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.

  PMID: 37169504 DERIVED

MeSH Terms

Conditions

Arthritis, Rheumatoid

Interventions

Exercise; High-Intensity Interval Training

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Motor Activity; Movement; Musculoskeletal Physiological Phenomena; Musculoskeletal and Neural Physiological Phenomena; Physical Conditioning, Human

Study Officials

• Regitse Christensen

  Center for Physical Activity Research, Rigshospitalet

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal investigator

Study Record Dates

• First Submitted: November 16, 2021
• First Posted: January 31, 2022
• Study Start: January 1, 2021
• Primary Completion: August 10, 2023
• Study Completion: December 31, 2023
• Last Updated: February 2, 2024

Record last verified: 2024-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: SAP, ICF, CSR, ANALYTIC CODE
• 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.
• 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)

Locations

DK (1)