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

Rheumatoid Arthritis Clinical Trial

— RABEX  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05215509
• Other study ID #: H-21010559
• Status: Completed
• Phase: N/A
• Start date: January 1, 2021
• Est. completion date: December 31, 2023

Study information

• Verified date: February 2024
• Source: Rigshospitalet, Denmark
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 69
• Est. completion date: December 31, 2023
• Est. primary completion date: August 10, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• Arthritis
• Arthritis, Rheumatoid
• Rheumatoid Arthritis

Intervention

Behavioral:
• Exercise
Supervised high-intensity interval training for 12 weeks three times per week. The supervision may be physical or online supervision
• No exercise
Control group, therefore no supervised exercise regime

Locations

Country	Name	City	State
Denmark	Rigshospitalet	Copenhagen

Sponsors (1)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in left ventricular mass	measured by MRI scan	12 weeks
Secondary	Visceral adipose tissue mass	measured by MRI scan	12 weeks
Secondary	Stroke volume	Structural cardiac parameter: measured by MRI scan and echocardiography	12 weeks
Secondary	Left ventricular and atrial end-diastolic volume	Structural cardiac parameter: measured by MRI scan and echocardiography	12 weeks
Secondary	LVEF	Functional cardiac parameters: measured by MRI scan and echocardiography	12 weeks
Secondary	Global longitudinal strain	Functional cardiac parameters: measured by MRI scan and echocardiography	12 weeks
Secondary	E/A ratio	Functional cardiac parameters: measured by MRI scan and echocardiography	12 weeks
Secondary	E/é	Functional cardiac parameters: measured by MRI scan and echocardiography	12 weeks
Secondary	Left ventricular and atrial end-systolic volume	Structural cardiac parameter: measured by MRI scan and echocardiography	12 weeks
Secondary	Left atrial volume index	Structural cardiac parameter: measured by MRI scan and echocardiography	12 weeks
Secondary	Interventricular septum thickness	Structural cardiac parameter: measured by MRI scan and echocardiography	12 weeks
Secondary	Left ventricular posterior wall thickness	Structural cardiac parameter: measured by MRI scan and echocardiography	12 weeks
Secondary	Aortic and pulmonary distensibility and pulse wave velocity	Functional vascular parameter: measured by MRI	12 weeks
Secondary	Subcutaneous, visceral and epicardial adipose tissue	Measured by MRI and MR spectroscopy	12 weeks
Secondary	Intramyocardial triglyceride content	Measured by MRI and MR spectroscopy	12 weeks
Secondary	Cardiorespiratory fitness	Measured with an incremental VO2 protocol on exercise bike	12 weeks
Secondary	Dynamic spirometry	Pulmonary function testing	12 weeks
Secondary	Whole body plethysmography	Pulmonary function testing	12 weeks
Secondary	Diffusion capacity	Pulmonary function testing	12 weeks
Secondary	Body composition	Measured by a DXA scan	12 weeks
Secondary	Oral glucose tolerance test	75g of glucose taken while fasting	12 weeks
Secondary	Axial accelerometer-based physical activity monitors	Free-living physical activity is measured using axial accelerometer-based physical activity monitors (AX3; Axivity, Newcastle upon Tyne, UK) for a 5-day period	5 days in week 6 of the intervention/control
Secondary	Dietary intake	Self reported intake of all foods and liquids	3 days in the week 6 of intervention/control
Secondary	Blood sample	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.	12 weeks
Secondary	Blood sample	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.	12 weeks
Secondary	RA disease specific outcomes 1	Change in measures of the international Core Outcome Set for rheumatoid arthritis : 66/68 tender and swollen joint count	12 weeks
Secondary	RA disease specific outcomes 2	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)	12 weeks
Secondary	RA disease specific outcomes 3	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.	12 weeks
Secondary	RA disease specific outcomes 4	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.	12 weeks
Secondary	RA disease specific outcomes 5	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	12 weeks
Secondary	RA disease specific outcomes 6	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	12 weeks
Secondary	RA disease specific outcomes 7	Change in response criteria will be assessed according the American College of Rheumatology (ACR 20/50/70) response	12 weeks
Secondary	RA disease specific outcomes 8	Change in response criteria will be assessed according the European League Against Rheumatism (EULAR none/good/moderate response)	12 weeks