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Completed

NCT Number: NCT05478018

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

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Center for Physical Activity Research

Copenhagen, 2200, Denmark

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

High Intensity Interval Training (HIIT)

Behavioral

Supervised high-intensity interval training for 12 weeks three times per week

Other names: Aerobic Exercise

Primary outcomes

  1. Changes in maximal aerobic capacity (VO2max)

    Time frame: 12 weeks

    Measured by VO2max test

  2. Patient reported Fatigue

    Time frame: 12 weeks

    measured by Fatigue Severity Scale Questionnaire (FSS)

Secondary outcomes

  1. Y2K updated SLE disease activity (SLEDAI-2K) with the SELENA modifications

    Time frame: 12 weeks

    Physician evaluated changes in measures of SLE on a scale of 0-105 encompassing symptoms from 9 organs, higher scores indicate increased disease activity.

  2. Short Form (SF)-36 Health Survey (0-100)

    Time frame: 12 weeks

    Patient reported outcome measures (PROMs), Possible scores range from 0 to 100, with higher scores representing better health status

  3. Change in Epigenetic Expression related to IFN alpha

    Time frame: 12 weeks

    Measured by mRNA analysis

Other outcomes

  1. Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 (SRI-50)

    Time frame: 12 weeks

    Itemized Physician evaluated changes in measures of SLEDAI-2K on a scale from 0-22 that account for partial improvements in condition, higher scores indicate increased disease activity.

  2. Visual Analog Scale (VAS) of global disease by Physician (0-100%)

    Time frame: 12 weeks

    Physician evaluated changes in measures of SLE (0-100% of line segment), higher scores equal higher disease activity (worse)

  3. Visual Analog Scale (VAS) fatigue (0-100)

    Time frame: 12 weeks

    Patient reported outcome measures (PROMs) , higher scores equal higher fatigue (worse)

  4. Visual Analog Scale (VAS) pain (0-100)

    Time frame: 12 weeks

    Patient reported outcome measures (PROMs), higher scores equal more pain (worse)

  5. SLAQ - (range 0 -33)

    Time frame: 12 weeks

    Patient reported outcome measures (PROMs), Possible scores range from 0 to 33, with higher scores representing more active SLE (worse)

  6. SLE activity Visual Analog Scale - (1-10)

    Time frame: 12 weeks

    Patient reported outcome measures (PROMs), Possible scores range from 1 to 10, with higher scores representing more active SLE

  7. Proteinuria

    Time frame: 12 weeks

    Measured by Dipstick in a semiquantitive manner with the following categories indicating increased concentration, negative, +/-, 1+, 2+, 3+, 4+.

  8. Body composition - Total adipose tissue - Weight

    Time frame: 12 weeks

    Measured by DXA Scan - fat(g)

  9. Body composition - Total adipose tissue - Percentage

    Time frame: 12 weeks

    Measured by DXA Scan - fat(%)

  10. Body composition - Android adipose tissue - Weight

    Time frame: 12 weeks

    Measured by DXA Scan - android fat(g)

  11. Body composition - Android adipose tissue - Percentage

    Time frame: 12 weeks

    Measured by DXA Scan - android fat(%)

  12. Body composition - Gyneoid adipose tissue - Weight

    Time frame: 12 weeks

    Measured by DXA Scan - Gyneoid fat(g)

  13. Body composition - Gyneoid adipose tissue - Percentage

    Time frame: 12 weeks

    Measured by DXA Scan - Gyneoid fat(%)

  14. Body composition - Total Lean Mass - Weight

    Time frame: 12 weeks

    Measured by DXA Scan - Muscle Mass(g)

  15. Body composition - Bone Mass Density - Weight/square-centimeter

    Time frame: 12 weeks

    Measured by DXA Scan - BMD(g/cm^2)

  16. Waist-To-Height Ratio

    Time frame: 12 weeks

    measured with tape measure

  17. Dynamic Spirometry - Forced Expiratory Volume at 1 second (FEV1) volume

    Time frame: 12 weeks

    Pulmonary function testing, FEV1 volume

  18. Dynamic Spirometry - Forced Expiratory Volume at 1 second (FEV1) Percent of expected

    Time frame: 12 weeks

    Pulmonary function testing, FEV1%

  19. Dynamic Spirometry - Forced Vital Capacity Volume

    Time frame: 12 weeks

    Pulmonary function testing, FVC Volume

  20. Dynamic Spirometry - Forced Vital Capacity - Percent of Expected

    Time frame: 12 weeks

    Pulmonary function testing FVC%

  21. Dynamic Spirometry Forced Expiratory Volume at 1 second (FEV1) by Forced Vital Capacity - Ratio

    Time frame: 12 weeks

    Pulmonary function testing, FEV1/FVC ratio

  22. Dynamic Spirometry Forced Expiratory Volume at 1 second (FEV1) by Forced Vital Capacity - Ratio - Percentage of expected

    Time frame: 12 weeks

    Pulmonary function testing, FEV1/FVC ratio %

  23. Dynamic Spirometry - Total Lung Capacity - Volume

    Time frame: 12 weeks

    Pulmonary function testing, TLC Volume

  24. Dynamic Spirometry - Total Lung Capacity - Percentage of expected

    Time frame: 12 weeks

    Pulmonary function testing, TLC%

  25. Dynamic Spirometry - Residual Volume - Volume

    Time frame: 12 weeks

    Pulmonary function testing, RV-Volume

  26. Dynamic Spirometry - Residual Volume - Percentage of Expected

    Time frame: 12 weeks

    Pulmonary function testing, RV%

  27. Dynamic Spirometry - Alveolar Volume - Volume

    Time frame: 12 weeks

    Pulmonary function testing, AV-Volume

  28. Dynamic Spirometry - Alveolar Volume - Percentage of expected

    Time frame: 12 weeks

    Pulmonary function testing, AV-%

  29. Dynamic Spirometry - Diffusing capacity for Carbon Monoxide - Volume

    Time frame: 12 weeks

    Pulmonary function testing, DLCOc-Volume

  30. Dynamic Spirometry - Diffusing capacity for Carbon Monoxide - Percentage

    Time frame: 12 weeks

    Pulmonary function testing, DLCOc-%

  31. Dynamic Spirometry - Carbon monoxide transfer coefficient - diffusing capacity per liter of lung volume

    Time frame: 12 weeks

    Pulmonary function testing, KCO-Volume

  32. Dynamic Spirometry - Carbon monoxide transfer coefficient - diffusing capacity per liter of lung volume - percentage of expected

    Time frame: 12 weeks

    Pulmonary function testing, KCO-%

  33. Oral glucose tolerance test

    Time frame: 12 weeks

    75g of glucose taken while fasting

  34. Peripheral Capillary Changes - Capillary Density

    Time frame: 12 weeks

    Measured by Nailfold Capillaroscopy by trained physician (score of 1-4, higher scores equal fewer capillaries)

  35. Peripheral Capillary Changes - Average Capillary Width (micrometers)

    Time frame: 12 weeks

    Measured by Nailfold Capillaroscopy by trained physician - Width Measured in µm

  36. Peripheral Capillary Changes - Average Capillary Length(micrometers)

    Time frame: 12 weeks

    Measured by Nailfold Capillaroscopy by trained physician - Length Measured in µm

  37. Peripheral Capillary Changes - Count of avascular areas

    Time frame: 12 weeks

    Measured by Nailfold Capillaroscopy by trained physician - Avascular Areas (1-4 higher scores indicate more avascular areas)

  38. Peripheral Capillary Changes - Capillary Disorganization

    Time frame: 12 weeks

    Measured by Nailfold Capillaroscopy by trained physician - Capillary Disorganization (1-4 higher scores indicate more avascular areas)

  39. Peripheral Capillary Changes - Microhemorrhages (average per finger)

    Time frame: 12 weeks

    Measured by Nailfold Capillaroscopy by trained physician - Microhemorrhages (avg per finger)

  40. Peripheral Capillary Changes - Bushy Capillaries (average per millimeter)

    Time frame: 12 weeks

    Measured by Nailfold Capillaroscopy by trained physician - Bushy Capillaries (average per millimeter)

  41. Peripheral Capillary Changes - Megacapillaries (average per millimeter)

    Time frame: 12 weeks

    Measured by Nailfold Capillaroscopy by trained physician - Megacapillaries (average per millimeter)

  42. Peripheral Capillary Changes - Meandering capillaries (average per millimeter)

    Time frame: 12 weeks

    Measured by Nailfold Capillaroscopy by trained physician - Meandering capillaries (average per millimeter)

  43. Peripheral Capillary Changes - Tortous capillaries (average per millimeter)

    Time frame: 12 weeks

    Measured by Nailfold Capillaroscopy by trained physician - Tortous capillaries (average per millimeter)

  44. Peripheral Capillary Changes - Other Findings

    Time frame: 12 weeks

    Measured by Nailfold Capillaroscopy by trained physician - Physicians comment

  45. Change in fasting total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol (mmol/L). Following an overnight fast (10 hours)

    Time frame: 12 weeks

    blood samples are collected and processed by a trained laboratory technician and analysed according to standard procedures.monitors (AX3; Axivity, Newcastle upon Tyne, UK) for a 3 to 5 day period

  46. Change in triglycerides (mmol/L). Following an overnight fast (10 hours)

    Time frame: 12 weeks

    blood samples are collected and processed by a trained laboratory technician and analysed according to standard procedures.monitors (AX3; Axivity, Newcastle upon Tyne, UK) for a 3 to 5 day period

  47. left ventricular and atrial end-diastolic volume

    Time frame: 12 weeks

    measured by echocardiography

  48. global longitudinal strain

    Time frame: 12 weeks

    measured by echocardiography

  49. stroke volume

    Time frame: 12 weeks

    measured by echocardiography

  50. left ventricular ejection fraction

    Time frame: 12 weeks

    measured by echocardiography

  51. Left ventricular mass

    Time frame: 12 weeks

    measured by echocardiography

  52. coronary perfusion reserve

    Time frame: 12 weeks

    measured by echocardiography (& 82Rb-PET-CT)

  53. Myocardial blood flow

    Time frame: 12 weeks

    Measured by 82Rb-Pet-CT, on a subset of 40 participants

  54. Axial accelerometer-based physical activity monitors

    Time frame: 12 weeks

    Free-living physical activity is measured using axial accelerometer-based physical activity monitors (AX3; Axivity, Newcastle upon Tyne, UK) for a 3 to 5 day period

  55. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for High Sensitvity C-Reactive Protein

    Time frame: 12 weeks

    Analyzed for HS-CRP

  56. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Il-6

    Time frame: 12 weeks

    Analyzed for Il-6

  57. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for sIL-6r

    Time frame: 12 weeks

    Analyzed for soluble Il-6-receptor

  58. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Il-1

    Time frame: 12 weeks

    Analyzed for Il-1

  59. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Il-10

    Time frame: 12 weeks

    Analyzed for Il-10

  60. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for IFNα

    Time frame: 12 weeks

    Analyzed for IFNα

  61. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for IFNγ

    Time frame: 12 weeks

    Analyzed for IFNγ

  62. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for hgb

    Time frame: 12 weeks

    Analyzed for hemoglobin

  63. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for plates

    Time frame: 12 weeks

    Analyzed for thrombocytes

  64. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Na

    Time frame: 12 weeks

    Analyzed for sodium

  65. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for K

    Time frame: 12 weeks

    Analyzed for potassium

  66. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Cl

    Time frame: 12 weeks

    Analyzed for chloride

  67. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for hct

    Time frame: 12 weeks

    Analyzed for hematocrit.

  68. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Ferritin

    Time frame: 12 weeks

    Analyzed for ferritin

  69. Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for leucocyte differential

    Time frame: 12 weeks

    Analyzed for Leukocyte Differential

  70. Change in Epigenetic Expression related to IFN Beta

    Time frame: 12 weeks

    Measured by mRNA analysis on PBMCs

  71. Change in Epigenetic Expression related to IFN Gamma

    Time frame: 12 weeks

    Measured by mRNA analysis

  72. Change in Epigenetic Expression related to TNF

    Time frame: 12 weeks

    Measured by mRNA analysis

  73. Change in Epigenetic Expression related to IL-6

    Time frame: 12 weeks

    Measured by mRNA analysis on PBMCs

  74. Dietary Changes - Energy intake (kJ/day)

    Time frame: 12 weeks

    Patient Reported by dietary diary

  75. Dietary Changes - carbohydrate intake (g/day)

    Time frame: 12 weeks

    Patient Reported by dietary diary

  76. Dietary Changes - lipid intake (g/day)

    Time frame: 12 weeks

    Patient Reported by dietary diary

  77. Dietary Changes - Protein intake (g/day)

    Time frame: 12 weeks

    Patient Reported by dietary diary

  78. Dietary Changes - Other intake (categorical)

    Time frame: 12 weeks

    Patient Reported by dietary diary

  79. Muscle Biopsy for epigenetic markers of inflammation and myokine signalling

    Time frame: 12 weeks

    Optional for Participants: mRNA expression of genes related to TNF, IL-6, IFN alpha, beta and Gamma signalling

  80. Muscle Biopsy for epigenetic markers of physical activity

    Time frame: 12 weeks

    Optional for Participants: NF-κB p65 DNA binding activity (ELISA), phosphorylated and total JNK, phosphorylated AMPK (p-AMPK) total AMPK (Western blotting).

  81. Muscle Biopsy for epigenetic markers of physical activity - NF-κB p65 DNA binding activity (ELISA)

    Time frame: 12 weeks

    Optional for Participants: NF-κB p65 DNA binding activity (ELISA) & NF-κB binding activity (Western blotting).

  82. Muscle Biopsy for epigenetic markers of physical activity - c-Jun N-terminal kinase

    Time frame: 12 weeks

    Optional for Participants: phosphorylated and total JNK,

  83. Muscle Biopsy for epigenetic markers of physical activity - AMP-activated protein kinase

    Time frame: 12 weeks

    Optional for Participants: phosphorylated AMPK (p-AMPK) total AMPK (Western blotting).

  84. Autonomic Nerve Function Test - Resting HR by Vagus(tm)

    Time frame: 12 weeks

    Resting heart rate measured by R-R intervals on 1-lead ECG

  85. Autonomic Nerve Function Test - Rise from supine ratio of RR by Vagus(tm)

    Time frame: 12 weeks

    Rise from supine ratio of R-R intervals on 1-lead ECG

  86. Autonomic Nerve Function Test - Expiration Inspiration ratio of RR by Vagus(tm)

    Time frame: 12 weeks

    Expiration/Inspiration ratio of R-R intervals on 1-lead ECG

  87. Autonomic Nerve Function Test - Valsalva Maneuver ratio of RR by Vagus(tm)

    Time frame: 12 weeks

    Valsalva Maneuver ratio of R-R intervals on 1-lead ECG

Sponsors and collaborators

Lead sponsor

Rigshospitalet, Denmark

Other

Collaborators

  • Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Rigshospitalet

Registry information

Official study title

Type 1 Interferon Induced Changes to Exercise Adaptations in Systemic Lupus

Acronym: LUPEX

Important dates

Study start
2022
Primary completion
2024
Study completion
2025
First posted
Jul 28, 2022
Registry last updated
Sep 9, 2025

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