Clinical trial NCT05478018: Type 1 Interferon Induced Changes to Exercise Adaptations in Systemic Lupus Erythematosus Patients
Official title: Type 1 Interferon Induced Changes to Exercise Adaptations in Systemic Lupus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Systemic Lupus Erythematosus
Interferon Deficiency
Keywords: Cardiac adaptations
Metabolic adaptations
High intensity interval training
Interleukin-6 signature
Tumor necrosis factor signature
Interferon signature
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Rigshospitalet
First posted: 2022-07-28
Enrollment: 55
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

55 patients was included in a 12-week investigator blinded 1:1 randomised high intensity aerobic exercise intervention study.

Detailed description: 55 patients with SLE have been included and randomized in a 1:1 fashion to a 12 week high intensity interval training (HIIT) course or standard care.

Randomization was 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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in maximal aerobic capacity (VO2max)
timeFrame: 12 weeks
measure: Patient reported Fatigue
timeFrame: 12 weeks
Secondary outcomes:
measure: Y2K updated SLE disease activity (SLEDAI-2K) with the SELENA modifications
timeFrame: 12 weeks
measure: Short Form (SF)-36 Health Survey (0-100)
timeFrame: 12 weeks
measure: Change in Epigenetic Expression related to IFN alpha
timeFrame: 12 weeks
Other outcomes:
measure: Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 (SRI-50)
timeFrame: 12 weeks
measure: Visual Analog Scale (VAS) of global disease by Physician (0-100%)
timeFrame: 12 weeks
measure: Visual Analog Scale (VAS) fatigue (0-100)
timeFrame: 12 weeks
measure: Visual Analog Scale (VAS) pain (0-100)
timeFrame: 12 weeks
measure: SLAQ - (range 0 -33)
timeFrame: 12 weeks
measure: SLE activity Visual Analog Scale - (1-10)
timeFrame: 12 weeks
measure: Proteinuria
timeFrame: 12 weeks
measure: Body composition - Total adipose tissue - Weight
timeFrame: 12 weeks
measure: Body composition - Total adipose tissue - Percentage
timeFrame: 12 weeks
measure: Body composition - Android adipose tissue - Weight
timeFrame: 12 weeks
measure: Body composition - Android adipose tissue - Percentage
timeFrame: 12 weeks
measure: Body composition - Gyneoid adipose tissue - Weight
timeFrame: 12 weeks
measure: Body composition - Gyneoid adipose tissue - Percentage
timeFrame: 12 weeks
measure: Body composition - Total Lean Mass - Weight
timeFrame: 12 weeks
measure: Body composition - Bone Mass Density - Weight/square-centimeter
timeFrame: 12 weeks
measure: Waist-To-Height Ratio
timeFrame: 12 weeks
measure: Dynamic Spirometry - Forced Expiratory Volume at 1 second (FEV1) volume
timeFrame: 12 weeks
measure: Dynamic Spirometry - Forced Expiratory Volume at 1 second (FEV1) Percent of expected
timeFrame: 12 weeks
measure: Dynamic Spirometry - Forced Vital Capacity Volume
timeFrame: 12 weeks
measure: Dynamic Spirometry - Forced Vital Capacity - Percent of Expected
timeFrame: 12 weeks
measure: Dynamic Spirometry Forced Expiratory Volume at 1 second (FEV1) by Forced Vital Capacity - Ratio
timeFrame: 12 weeks
measure: Dynamic Spirometry Forced Expiratory Volume at 1 second (FEV1) by Forced Vital Capacity - Ratio - Percentage of expected
timeFrame: 12 weeks
measure: Dynamic Spirometry - Total Lung Capacity - Volume
timeFrame: 12 weeks
measure: Dynamic Spirometry - Total Lung Capacity - Percentage of expected
timeFrame: 12 weeks
measure: Dynamic Spirometry - Residual Volume - Volume
timeFrame: 12 weeks
measure: Dynamic Spirometry - Residual Volume - Percentage of Expected
timeFrame: 12 weeks
measure: Dynamic Spirometry - Alveolar Volume - Volume
timeFrame: 12 weeks
measure: Dynamic Spirometry - Alveolar Volume - Percentage of expected
timeFrame: 12 weeks
measure: Dynamic Spirometry - Diffusing capacity for Carbon Monoxide - Volume
timeFrame: 12 weeks
measure: Dynamic Spirometry - Diffusing capacity for Carbon Monoxide - Percentage
timeFrame: 12 weeks
measure: Dynamic Spirometry - Carbon monoxide transfer coefficient - diffusing capacity per liter of lung volume
timeFrame: 12 weeks
measure: Dynamic Spirometry - Carbon monoxide transfer coefficient - diffusing capacity per liter of lung volume - percentage of expected
timeFrame: 12 weeks
measure: Oral glucose tolerance test
timeFrame: 12 weeks
measure: Peripheral Capillary Changes - Capillary Density
timeFrame: 12 weeks
measure: Peripheral Capillary Changes - Average Capillary Width (micrometers)
timeFrame: 12 weeks
measure: Peripheral Capillary Changes - Average Capillary Length(micrometers)
timeFrame: 12 weeks
measure: Peripheral Capillary Changes - Count of avascular areas
timeFrame: 12 weeks
measure: Peripheral Capillary Changes - Capillary Disorganization
timeFrame: 12 weeks
measure: Peripheral Capillary Changes - Microhemorrhages (average per finger)
timeFrame: 12 weeks
measure: Peripheral Capillary Changes - Bushy Capillaries (average per millimeter)
timeFrame: 12 weeks
measure: Peripheral Capillary Changes - Megacapillaries (average per millimeter)
timeFrame: 12 weeks
measure: Peripheral Capillary Changes - Meandering capillaries (average per millimeter)
timeFrame: 12 weeks
measure: Peripheral Capillary Changes - Tortous capillaries (average per millimeter)
timeFrame: 12 weeks
measure: Peripheral Capillary Changes - Other Findings
timeFrame: 12 weeks
measure: Change in fasting total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol (mmol/L). Following an overnight fast (10 hours)
timeFrame: 12 weeks
measure: Change in triglycerides (mmol/L). Following an overnight fast (10 hours)
timeFrame: 12 weeks
measure: left ventricular and atrial end-diastolic volume
timeFrame: 12 weeks
measure: global longitudinal strain
timeFrame: 12 weeks
measure: stroke volume
timeFrame: 12 weeks
measure: left ventricular ejection fraction
timeFrame: 12 weeks
measure: Left ventricular mass
timeFrame: 12 weeks
measure: coronary perfusion reserve
timeFrame: 12 weeks
measure: Myocardial blood flow
timeFrame: 12 weeks
measure: Axial accelerometer-based physical activity monitors
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for High Sensitvity C-Reactive Protein
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Il-6
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for sIL-6r
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Il-1
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Il-10
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for IFNα
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for IFNγ
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for hgb
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for plates
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Na
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for K
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Cl
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for hct
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Ferritin
timeFrame: 12 weeks
measure: Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for leucocyte differential
timeFrame: 12 weeks
measure: Change in Epigenetic Expression related to IFN Beta
timeFrame: 12 weeks
measure: Change in Epigenetic Expression related to IFN Gamma
timeFrame: 12 weeks
measure: Change in Epigenetic Expression related to TNF
timeFrame: 12 weeks
measure: Change in Epigenetic Expression related to IL-6
timeFrame: 12 weeks
measure: Dietary Changes - Energy intake (kJ/day)
timeFrame: 12 weeks
measure: Dietary Changes - carbohydrate intake (g/day)
timeFrame: 12 weeks
measure: Dietary Changes - lipid intake (g/day)
timeFrame: 12 weeks
measure: Dietary Changes - Protein intake (g/day)
timeFrame: 12 weeks
measure: Dietary Changes - Other intake (categorical)
timeFrame: 12 weeks
measure: Muscle Biopsy for epigenetic markers of inflammation and myokine signalling
timeFrame: 12 weeks
measure: Muscle Biopsy for epigenetic markers of physical activity
timeFrame: 12 weeks
measure: Muscle Biopsy for epigenetic markers of physical activity - NF-κB p65 DNA binding activity (ELISA)
timeFrame: 12 weeks
measure: Muscle Biopsy for epigenetic markers of physical activity - c-Jun N-terminal kinase
timeFrame: 12 weeks
measure: Muscle Biopsy for epigenetic markers of physical activity - AMP-activated protein kinase
timeFrame: 12 weeks
measure: Autonomic Nerve Function Test - Resting HR by Vagus(tm)
timeFrame: 12 weeks
measure: Autonomic Nerve Function Test - Rise from supine ratio of RR by Vagus(tm)
timeFrame: 12 weeks
measure: Autonomic Nerve Function Test - Expiration Inspiration ratio of RR by Vagus(tm)
timeFrame: 12 weeks
measure: Autonomic Nerve Function Test - Valsalva Maneuver ratio of RR by Vagus(tm)
timeFrame: 12 weeks
Locations:
city: Copenhagen
country: Denmark
facility: Center for Physical Activity Research
Study officials:
affiliation: Center for Physical Activity Research
name: Ronan Martin G Berg, MD, DMSc
role: STUDY_CHAIR
affiliation: Center for Physical Activity Research
name: Iben E Rasmussen, MSc
role: STUDY_CHAIR
affiliation: Center for Physical Activity Research
name: Simon Jønck, MD
role: STUDY_CHAIR
affiliation: Center for Physical Activity Research
name: Malte L Adamsen, MD
role: PRINCIPAL_INVESTIGATOR
References: