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

Systemic Lupus Erythematosus Clinical Trial

— LUPEX  

Official title:

Type 1 Interferon Induced Changes to Exercise Adaptations in Systemic Lupus

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05478018
• Other study ID #: H-21039032
• Status: Active, not recruiting
• Phase: N/A
• Start date: April 1, 2022
• Est. completion date: September 1, 2024

Study information

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

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 55
• Est. completion date: September 1, 2024
• Est. primary completion date: April 16, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Interferon Deficiency
• Lupus Erythematosus, Systemic
• Systemic Lupus Erythematosus

Intervention

Behavioral:
• High Intensity Interval Training
Supervised high-intensity interval training for 12 weeks three times per week

Locations

Country	Name	City	State
Denmark	Center for Physical Activity Research	Copenhagen

Sponsors (2)

Lead Sponsor	Collaborator
Rigshospitalet, Denmark	Copenhagen Lupus and Vasculitis Clinic, Center for Rheumatology and Spine Diseases, Rigshospitalet

Country where clinical trial is conducted

Denmark, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Systemic Lupus Erythematosus Disease Activity Index 2000 Responder Index-50 (SRI-50)	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.	12 weeks
Other	Visual Analog Scale (VAS) of global disease by Physician (0-100%)	Physician evaluated changes in measures of SLE (0-100% of line segment), higher scores equal higher disease activity (worse)	12 weeks
Other	Visual Analog Scale (VAS) fatigue (0-100)	Patient reported outcome measures (PROMs) , higher scores equal higher fatigue (worse)	12 weeks
Other	Visual Analog Scale (VAS) pain (0-100)	Patient reported outcome measures (PROMs), higher scores equal more pain (worse)	12 weeks
Other	SLAQ - (range 0 -33)	Patient reported outcome measures (PROMs), Possible scores range from 0 to 33, with higher scores representing more active SLE (worse)	12 weeks
Other	SLE activity Visual Analog Scale - (1-10)	Patient reported outcome measures (PROMs), Possible scores range from 1 to 10, with higher scores representing more active SLE	12 weeks
Other	Proteinuria	Measured by Dipstick in a semiquantitive manner with the following categories indicating increased concentration, negative, +/-, 1+, 2+, 3+, 4+.	12 weeks
Other	Body composition - Total adipose tissue - Weight	Measured by DXA Scan - fat(g)	12 weeks
Other	Body composition - Total adipose tissue - Percentage	Measured by DXA Scan - fat(%)	12 weeks
Other	Body composition - Android adipose tissue - Weight	Measured by DXA Scan - android fat(g)	12 weeks
Other	Body composition - Android adipose tissue - Percentage	Measured by DXA Scan - android fat(%)	12 weeks
Other	Body composition - Gyneoid adipose tissue - Weight	Measured by DXA Scan - Gyneoid fat(g)	12 weeks
Other	Body composition - Gyneoid adipose tissue - Percentage	Measured by DXA Scan - Gyneoid fat(%)	12 weeks
Other	Body composition - Total Lean Mass - Weight	Measured by DXA Scan - Muscle Mass(g)	12 weeks
Other	Body composition - Bone Mass Density - Weight/square-centimeter	Measured by DXA Scan - BMD(g/cm^2)	12 weeks
Other	Waist-To-Height Ratio	measured with tape measure	12 weeks
Other	Dynamic Spirometry - Forced Expiratory Volume at 1 second (FEV1) volume	Pulmonary function testing, FEV1 volume	12 weeks
Other	Dynamic Spirometry - Forced Expiratory Volume at 1 second (FEV1) Percent of expected	Pulmonary function testing, FEV1%	12 weeks
Other	Dynamic Spirometry - Forced Vital Capacity Volume	Pulmonary function testing, FVC Volume	12 weeks
Other	Dynamic Spirometry - Forced Vital Capacity - Percent of Expected	Pulmonary function testing FVC%	12 weeks
Other	Dynamic Spirometry Forced Expiratory Volume at 1 second (FEV1) by Forced Vital Capacity - Ratio	Pulmonary function testing, FEV1/FVC ratio	12 weeks
Other	Dynamic Spirometry Forced Expiratory Volume at 1 second (FEV1) by Forced Vital Capacity - Ratio - Percentage of expected	Pulmonary function testing, FEV1/FVC ratio %	12 weeks
Other	Dynamic Spirometry - Total Lung Capacity - Volume	Pulmonary function testing, TLC Volume	12 weeks
Other	Dynamic Spirometry - Total Lung Capacity - Percentage of expected	Pulmonary function testing, TLC%	12 weeks
Other	Dynamic Spirometry - Residual Volume - Volume	Pulmonary function testing, RV-Volume	12 weeks
Other	Dynamic Spirometry - Residual Volume - Percentage of Expected	Pulmonary function testing, RV%	12 weeks
Other	Dynamic Spirometry - Alveolar Volume - Volume	Pulmonary function testing, AV-Volume	12 weeks
Other	Dynamic Spirometry - Alveolar Volume - Percentage of expected	Pulmonary function testing, AV-%	12 weeks
Other	Dynamic Spirometry - Diffusing capacity for Carbon Monoxide - Volume	Pulmonary function testing, DLCOc-Volume	12 weeks
Other	Dynamic Spirometry - Diffusing capacity for Carbon Monoxide - Percentage	Pulmonary function testing, DLCOc-%	12 weeks
Other	Dynamic Spirometry - Carbon monoxide transfer coefficient - diffusing capacity per liter of lung volume	Pulmonary function testing, KCO-Volume	12 weeks
Other	Dynamic Spirometry - Carbon monoxide transfer coefficient - diffusing capacity per liter of lung volume - percentage of expected	Pulmonary function testing, KCO-%	12 weeks
Other	Oral glucose tolerance test	75g of glucose taken while fasting	12 weeks
Other	Peripheral Capillary Changes - Capillary Density	Measured by Nailfold Capillaroscopy by trained physician (score of 1-4, higher scores equal fewer capillaries)	12 weeks
Other	Peripheral Capillary Changes - Average Capillary Width (micrometers)	Measured by Nailfold Capillaroscopy by trained physician - Width Measured in µm	12 weeks
Other	Peripheral Capillary Changes - Average Capillary Length(micrometers)	Measured by Nailfold Capillaroscopy by trained physician - Length Measured in µm	12 weeks
Other	Peripheral Capillary Changes - Count of avascular areas	Measured by Nailfold Capillaroscopy by trained physician - Avascular Areas (1-4 higher scores indicate more avascular areas)	12 weeks
Other	Peripheral Capillary Changes - Capillary Disorganization	Measured by Nailfold Capillaroscopy by trained physician - Capillary Disorganization (1-4 higher scores indicate more avascular areas)	12 weeks
Other	Peripheral Capillary Changes - Microhemorrhages (average per finger)	Measured by Nailfold Capillaroscopy by trained physician - Microhemorrhages (avg per finger)	12 weeks
Other	Peripheral Capillary Changes - Bushy Capillaries (average per millimeter)	Measured by Nailfold Capillaroscopy by trained physician - Bushy Capillaries (average per millimeter)	12 weeks
Other	Peripheral Capillary Changes - Megacapillaries (average per millimeter)	Measured by Nailfold Capillaroscopy by trained physician - Megacapillaries (average per millimeter)	12 weeks
Other	Peripheral Capillary Changes - Meandering capillaries (average per millimeter)	Measured by Nailfold Capillaroscopy by trained physician - Meandering capillaries (average per millimeter)	12 weeks
Other	Peripheral Capillary Changes - Tortous capillaries (average per millimeter)	Measured by Nailfold Capillaroscopy by trained physician - Tortous capillaries (average per millimeter)	12 weeks
Other	Peripheral Capillary Changes - Other Findings	Measured by Nailfold Capillaroscopy by trained physician - Physicians comment	12 weeks
Other	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.monitors (AX3; Axivity, Newcastle upon Tyne, UK) for a 3 to 5 day period	12 weeks
Other	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.monitors (AX3; Axivity, Newcastle upon Tyne, UK) for a 3 to 5 day period	12 weeks
Other	left ventricular and atrial end-diastolic volume	measured by echocardiography	12 weeks
Other	global longitudinal strain	measured by echocardiography	12 weeks
Other	stroke volume	measured by echocardiography	12 weeks
Other	left ventricular ejection fraction	measured by echocardiography	12 weeks
Other	Left ventricular mass	measured by echocardiography	12 weeks
Other	coronary perfusion reserve	measured by echocardiography (& 82Rb-PET-CT)	12 weeks
Other	Myocardial blood flow	Measured by 82Rb-Pet-CT, on a subset of 40 participants	12 weeks
Other	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 3 to 5 day period	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for High Sensitvity C-Reactive Protein	Analyzed for HS-CRP	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Il-6	Analyzed for Il-6	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for sIL-6r	Analyzed for soluble Il-6-receptor	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Il-1	Analyzed for Il-1	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Il-10	Analyzed for Il-10	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for IFNa	Analyzed for IFNa	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for IFN?	Analyzed for IFN?	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for hgb	Analyzed for hemoglobin	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for plates	Analyzed for thrombocytes	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Na	Analyzed for sodium	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for K	Analyzed for potassium	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Cl	Analyzed for chloride	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for hct	Analyzed for hematocrit.	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for Ferritin	Analyzed for ferritin	12 weeks
Other	Change in peripheral blood Adaptation to Acute Exercise Bout - Analyzed for leucocyte differential	Analyzed for Leukocyte Differential	12 weeks
Other	Change in Epigenetic Expression related to IFN Beta	Measured by mRNA analysis on PBMCs	12 weeks
Other	Change in Epigenetic Expression related to IFN Gamma	Measured by mRNA analysis	12 weeks
Other	Change in Epigenetic Expression related to TNF	Measured by mRNA analysis	12 weeks
Other	Change in Epigenetic Expression related to IL-6	Measured by mRNA analysis on PBMCs	12 weeks
Other	Dietary Changes - Energy intake (kJ/day)	Patient Reported by dietary diary	12 weeks
Other	Dietary Changes - carbohydrate intake (g/day)	Patient Reported by dietary diary	12 weeks
Other	Dietary Changes - lipid intake (g/day)	Patient Reported by dietary diary	12 weeks
Other	Dietary Changes - Protein intake (g/day)	Patient Reported by dietary diary	12 weeks
Other	Dietary Changes - Other intake (categorical)	Patient Reported by dietary diary	12 weeks
Other	Muscle Biopsy for epigenetic markers of inflammation and myokine signalling	Optional for Participants: mRNA expression of genes related to TNF, IL-6, IFN alpha, beta and Gamma signalling	12 weeks
Other	Muscle Biopsy for epigenetic markers of physical activity	Optional for Participants: NF-?B p65 DNA binding activity (ELISA), phosphorylated and total JNK, phosphorylated AMPK (p-AMPK) total AMPK (Western blotting).	12 weeks
Other	Muscle Biopsy for epigenetic markers of physical activity - NF-?B p65 DNA binding activity (ELISA)	Optional for Participants: NF-?B p65 DNA binding activity (ELISA) & NF-?B binding activity (Western blotting).	12 weeks
Other	Muscle Biopsy for epigenetic markers of physical activity - c-Jun N-terminal kinase	Optional for Participants: phosphorylated and total JNK,	12 weeks
Other	Muscle Biopsy for epigenetic markers of physical activity - AMP-activated protein kinase	Optional for Participants: phosphorylated AMPK (p-AMPK) total AMPK (Western blotting).	12 weeks
Other	Autonomic Nerve Function Test - Resting HR by Vagus(tm)	Resting heart rate measured by R-R intervals on 1-lead ECG	12 weeks
Other	Autonomic Nerve Function Test - Rise from supine ratio of RR by Vagus(tm)	Rise from supine ratio of R-R intervals on 1-lead ECG	12 weeks
Other	Autonomic Nerve Function Test - Expiration Inspiration ratio of RR by Vagus(tm)	Expiration/Inspiration ratio of R-R intervals on 1-lead ECG	12 weeks
Other	Autonomic Nerve Function Test - Valsalva Maneuver ratio of RR by Vagus(tm)	Valsalva Maneuver ratio of R-R intervals on 1-lead ECG	12 weeks
Primary	Changes in maximal aerobic capacity (VO2max)	Measured by VO2max test	12 weeks
Primary	Patient reported Fatigue	measured by Fatigue Severity Scale Questionnaire (FSS)	12 weeks
Secondary	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
Secondary	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
Secondary	Change in Epigenetic Expression related to IFN alpha	Measured by mRNA analysis	12 weeks