Type 1 Interferon Induced Changes to Exercise Adaptations in Systemic Lupus Erythematosus Patients

Study Overview
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Brief Summary
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Investigating the physiological effects of the interferons type 1 and 2 (IFNs), and the cytokines Interleukin 6 (IL-6) and tumor necrosis factor (TNF) on the adaptive changes to exercise in patients with systemic lupus erythematosus (SLE). The investigators hypothesize that the pathogenic blockage of IL-6 signalling that occurs in SLE, will decrease the cardiac and metabolic adaptations to aerobic exercise, and this decrease can be related to the IFN signature. 60 patients will be included in a 12-week investigator blinded 1:1 randomised high intensity aerobic exercise intervention study.

Detailed Description
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60 patients with SLE, will be included and randomized in a 1:1 fashion to a 12 week high intensity interval training (HIIT) course or standard care. Randomization will be stratified by sex. All patients will undergo baseline and followup testing including: VO2Max, Pulmonary Function, Capillaroscopy, OGTT, Blood Tests, Epigenetic Markers of IFN, TNF and IL-6 signalling, Echocardiography,DXA, Medical Examination, Acute Exercise Bout with blood tests during and after an exercise bout similar to the intervention. A subgroup of patients will be offered a 82-Rb Pet CT of the heart as opt-in. The exercise programme consists of 12 weeks of tri-weekly exercise bouts of 38-45 minutes, following warm-up subjects will undergo 4 sets of 4 minute high intensity exercise, measured as the pulse being above 85% of HRmax for more than half the time; and 3 minute low to medium intensity exercise between the high intensity sets, measured as the pulse being between 40 to 60% of HRmax.

Official Title
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Type 1 Interferon Induced Changes to Exercise Adaptations in Systemic Lupus

Conditions
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Systemic Lupus Erythematosus, Interferon Deficiency

Intervention / Treatment
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* Behavioral: High Intensity Interval Training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years by inclusion. Able to provide informed consent. Diagnosed SLE and fulfilling the classification criteria for SLE based on the American College of Rheumatology/EULAR criteria (SLICC) Exclusion Criteria: Health conditions that prevent participating in the exercise intervention determined by the Research Coordinator these include but are not limited to Major bone fracture at inclusion Significant myalgias exacerbated by physical exercise Active infectious disease such as Covid-19 Severe symptomatic pleuritis or pericarditis Corticosteroid use > 10mg/day at baseline Diagnosed with diabetes mellitus by physician Pregnancy SLEDAI-2k (with the SELENA modifications to Proteinuria changes so as to not exclude patients with chronic proteinuria) > 10 Contraindications to 82Rb-PET with adenosine stress (according to local guidelines at the Dept. of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet, which are in accordance with the recommendations of the European Association of Nuclear Medicine) Fever, myocarditis or endocarditis Previous heart transplantation Dysregulated atrial or ventricular tachyarrhythmias Severe chronic obstructive pulmonary disease with a FEV1 of less than 50% of predicted Second or third degree sinoatrial or atrioventricular block Active bronchospasm at the time of the scan Systolic blood pressure <90 or >200 mmHg at the time of the scan Treatment with theophyllin within 7 days of the scan

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Exercise<br>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 3-10 min cool-down of 50% Hrmax | Behavioral: High Intensity Interval Training<br>* Supervised high-intensity interval training for 12 weeks three times per week<br>* Other names: Aerobic Exercise;|
| No Intervention: Non-Exercise<br>Control group, therefore no supervised exercise regime. Subjects are asked to not increase habitual exercise routines. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in maximal aerobic capacity (VO2max) | Measured by VO2max test | 12 weeks | 
| Patient reported Fatigue | measured by Fatigue Severity Scale Questionnaire (FSS) | 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Y2K updated SLE disease activity (SLEDAI-2K) with the SELENA modifications | Physician evaluated changes in measures of SLE on a scale of 0-105 encompassing symptoms from 9 organs, higher scores indicate increased disease activity. | 12 weeks | 
| Short Form (SF)-36 Health Survey (0-100) | Patient reported outcome measures (PROMs), Possible scores range from 0 to 100, with higher scores representing better health status | 12 weeks | 
| Change in Epigenetic Expression related to IFN alpha | Measured by mRNA analysis | 12 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Cardiac adaptations, Metabolic adaptations, High intensity interval training, Interleukin-6 signature, Tumor necrosis factor signature, Interferon signature