Systemic Lupus ErythematosusSLE-VNSNCT05315739

Vagus Nerve Stimulation for Systemic Lupus Erythematous

A study testing Non-invasive transcutaneous vagus nerve stimulation (tVNS) in people with Systemic Lupus Erythematosus and Autonomic Dysfunction, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This trial uses a double blinded, randomized 1:1 (active:sham) placebo controlled, parallel group design, investigating the effects of transcutaneous vagus nerve stimulation (tVNS) in patients with systemic lupus erythematosus (SLE). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Systemic Lupus Erythematosus, Autonomic Dysfunction, Autonomic Neuropathy
What is being tested?: Non-invasive transcutaneous vagus nerve stimulation (tVNS)
Type of treatment: Medical device
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 75 participants
Where: 1 siteDenmark
Study dates: 24 Aug 2022to 23 Aug 2023
Phase: Interventional
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Reading and understanding Danish.
SLE diagnosis based on SLE disease classification criteria for at least 1 year.
Stable disease and medication the past 28 days as defined by:
No change in disease modifying antirheumatic drugs or biological therapy,
Receiving maximally 10 mg prednisone daily.
Having signs of fatigue, as assessed by scoring ≤ 40 in the FACIT-Fatigue questionnaire.

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Having signs of autonomic dysfunction, as assessed by scoring one or more of:
VAGUS score ≥1
SUDOSCAN score < 50µS for hands or < 70µS for feet
COMPASS-31 score > 12
Patients willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other trial procedures.
Sign the dated informed consent documents

Who cannot join

Significant cardiovascular disease, including congenital cardiac disease, congestive heart failure, known severe coronary artery disease, or recent myocardial infarction (within 5 years), as assessed by a physician at the screening.
Blood pressure < 100/60 or > 160/105
Clinically significant bradycardia or tachycardia
History of abnormal baseline ECG, prolonged QT interval or arrhythmia
Previous surgery on the vagus nerve or abnormal cervical anatomy
Implanted or portable electro-mechanical medical devices, e.g. pacemaker, defibrillator, cochlear implant and infusion pump

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Metallic device such as a stent, bone plate or bone screw implanted at or near the neck
Receiving active laser treatment for proliferative retinopathy
Active cancer or cancer in remission
History of brain tumor, aneurysm, bleed, head trauma, clinically significant syncope or seizures
Any clinical abnormalities that, in the opinion of the investigator, may increase the risk associated with trial participation or may interfere with the interpretation of the trial results.
Participation in other clinical trials less than three months prior to inclusion, unless such a participation is judged to have no influence on the recordings
Female pregnancy (positive urine-HCG), ongoing lactation or intended pregnancy during the study period.
A pregnancy test is conducted at first and last visit to ensure that fertile female patients are not pregnant during the study period.
Further, the investigator ensures that fertile female patients use a safe contraception method during the study and for at least 15 hours after termination of the study period. Safe contraception: The combined oral contraceptive pill; intra uterine device; gestagen injection; subdermal implantation; hormone vaginal ring; and transdermal plaster.
Male patients who intend to father a child during the course of the study

Trial locations and contacts

1 site in 1 country.

Denmark1 site

Rigshospitalet
Copenhagen, 2100

Other trials in Denmark

About this study

Official title: Vagus Nerve Stimulation as a Novel Treatment for Systemic Lupus Erythematous: A Double Blinded Randomized Controlled Trail

The main objective is to evaluate whether adjuvant treatment with tVNS in SLE patients with signs of autonomic dysfunction and fatigue improves patient perceived levels of fatigue. Secondary outcomes include tVNS induced changes to: patient reported outcomes, autonomic nervous system function, SLE disease activity, immunologic profile, tolerability of pain and organ (cardiac, vascular and kidney) functions.

Participants are randomized to received either active non-invasive transcutaneous vagus nerve stimulation (tVNS) or inactive sham stimulation. The study period is divided in two periods. The first period investigates the effects of short-term, high-intensity tVNS treatment. The second phase investigates the effects of long-term, middle-intensity tVNS treatment.

Conditions: Systemic Lupus Erythematosus, Autonomic Dysfunction, Autonomic Neuropathy, Fatigue
Being tested: Non-invasive transcutaneous vagus nerve stimulation (tVNS), Sham vagus nerve stimulation
Keywords: Vagus Nerve Stimulation, Fatigue, Pain, Health-Related Quality Of Life, Autonomic Nervous System Disorders, Inflammation, Autoimmunity, Kidney Diseases, Vascular Diseases, Heart Diseases
Medical subject headings: Lupus Erythematosus, Systemic, Primary Dysautonomias, Fatigue, Pain, Autonomic Nervous System Diseases, Inflammation, Autoimmune Diseases, Kidney Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Non-invasive transcutaneous vagus nerve stimulation (tVNS)Device
Also called GammaCore Sapphire device
tVNS delivers an electrical current to the cervical branch of the vagus nerve. Four minutes of bilateral stimulation 4 times per day for 7 days (period 1) and 2 times per day for 8 weeks (period 2) are performed. The two periods are separated by a 2 weeks wash-out period.
Sham vagus nerve stimulationDevice
Also called GammaCore Sapphire sham device
The sham device produces a slight vibrating sound, but does not produce an electical current and hence, does not activate the vagus nerve.
Four minutes of bilateral stimulation 4 times per day for 7 days (period 1) and 2 times per day for 8 weeks (period 2). The two periods are separated by a 2 weeks wash-out period.

Study groups in NCT05315739
Study group	Role	What they receive
Active treatment	Active comparator	Non-invasive transcutaneous vagus nerve stimulation applied by the gammaCore device (electroCore) Receives: Device: Non-invasive transcutaneous vagus nerve stimulation (tVNS)
Sham treatment	Sham comparator	Inactive sham vagus nerve stimulation applied by the gammaCore sham device (electroCore) Receives: Device: Sham vagus nerve stimulation

What is being measured

The primary outcome is the main question the study is designed to answer.

Fatigue (changes during period 1 and 2)
The FACIT-Fatigue Scale is a short, 13-item, tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four-point scale for each item. The theoretical maximum value is 52 (maximal fatigue) and minimum 0 (no fatigue).
Measured: During period 1: At baseline, daily (day 2-6) until- and at follow-up (day 7). During period 2: At baseline, at day 7-visit, weekly (week 3-7) until- and at follow-up (week 8).

Secondary outcomes (28)

Questionnaire on autonomic symptoms: Composite Autonomic Symptoms Score 31 (COMPASS-31)
The COMPASS-31 is a validated questionnaire of 31 questions providing a quantitative measure of autonomic nervous system dysfunction symptoms. The score ranges from 0 (no symptoms) to 100 (most severe autonomic symptoms).
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Questionnaire on SLE disease activity: Patient Global Assessment (PtGA)
The participants rate their subjectively perceived disease activity on a scale from 0 to 10, in which 0 = no disease activity and 10 = worst imaginable disease activity.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit, weekly (week 3-7) until- and at follow-up (week 8).
Questionnaire on SLE disease activity: Systemic Lupus Activity Questionnaire (SLAQ)
In the SLAQ the participants rate their perceived disease activity by rating the severity of 24 disease activity related symptoms by either "no problem", "mild", "moderate" or "severe" In the SLAQ the participants rate their perceived disease activity by rating the severity of 24 disease activity related symptoms by either "no problem", "mild", "moderate" or "severe" and a Patient Global Disease Activity measure as mentioned in (3).
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit, and at follow-up (week 8).
Questionnaire on quality of life: Short form-12 (SF-12)
From the validated 12-item SF-12 a physical and mental component score of patient-reported health related quality of life is calculated. Component scores range from 0-100 (lowest to highest level of self-reported health) and are calculated by giving specific weights to each of the 12 individual items/questions, calculating a weighted sum, and finally adding the sum to a component specific constant.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit, and at follow-up (week 8).
Questionnaire on pain: Visual analog rating scale (VAS)
Participants will assess the level of musculoskeletal pain within the previous 7 days by scoring the level on the VAS (0 to 10, where 0 = no pain and 10 = worst imaginable pain).
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit, weekly (week 3-7) until- and at follow-up (week 8).
SLE disease activity: SLE Disease Activity Index 2000 (SLEDAI-2K)
The validated SLEDAI-2K entails 24 weighted descriptors of disease activity across 9 organ systems. The SLEDAI-2K-score ranges from 0 (no activity) to a theoretical maximum score of 105 and reports on manifestations occurring up to 10 days before the examination.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE disease activity: SLEDAI Responder Index 50% (SRI-50)
The SRI-50 is a validated derivation of SLEDAI-2K that considers clinically significant improvements (≥ 50%) between visits.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE disease activity: SLE Disease Activity Score (SLE-DAS)
The SLE-DAS is a validated index containing 17 clinical and laboratory descriptors and is a global measure of SLE disease activity suggested to have improved sensitivity to change and specificity as compared with the SLEDAI-2K.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE disease activity: Physician Global Assessment (PGA)
The PGA measures disease activity in SLE is determined by the physician's judgement of overall disease activity. It is scored by answering "How do you rate your patient's current disease activity?" with 1=mild, 2=moderate or 3=most active disease imaginable.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE disease activity: Painful and swollen joints
The number of painful and swollen joints are assessed according to the Disease Activity Score-28 (Swollen joints: 0 = no, and 28 = 28 swollen. Painful joints: 0 = n, and 28 = 28 painful joints).
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Autonomic function: Resting heart rate variability (HRV)
With the VagusTM device, 5 minutes of resting HRV is measured. Classical time (SDNN, RMSSD) and frequency (LF, HF, total and LF/HF) domain heart rate variability parameters will be assessed.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Autonomic function: Resting Cardiac Vagal Tone (CVT)
Cardiac vagal tone reflecting parasympathetic activity is measured through three chest electrocardiography electrodes. A cardiac monitor, the eMotion Faros device is attached to the electrodes and the electrocardiogram is sampled at 8 kHz for 5 minutes, from which the cardiac vagal tone is derived.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Autonomic function: Cardiovascular autonomic reflex tests - heart rate response
The heart rate response to three cardiovascular autonomic reflex tests are assessed with the VagusTM-device for estimation of the degree of autonomic dysfunction: The ratio of the maximum and minimum heart rate in relation to a) standing, b) deep breathing and, c) a Valsalva maneuver. By comparing results of the cardiovascular reflex tests with age-dependent cut-off levels, the degree of autonomic dysfunction is divided into categories: no, early (one) and manifest (two or three abnormal tests).
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Autonomic function: Cardiovascular autonomic reflex tests - blood pressure response
The blood pressure response to one cardiovascular autonomic reflex test is assessed. After a supine 5-min rest, the orthostatic blood pressure is measured. The participant stands for 5 minutes while the blood pressure is measured each minute. Blood pressure drops (systolic 20 mmHg or diastolic 10 mmHg) indicate impaired, especially, sympathetic function.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Autonomic function: Continuous heart rate and HRV monitoring
A small patch sensor (ePatch) will be used to monitor the heart rate variability during a period of 7 days. Classical time (RR-interval, SDNN, SDNNi, SDANN, RMSSD) and frequency (VLF, LF, HF and LF/HF) domain heart rate variability parameters will be assessed.
Measured: During period 1: From baseline to follow-up (day 7). During period 2: From baseline to day 7-visit.
Autonomic function: Sweat secretion
The Sudoscan® provides a quick, non-invasive and reproducible assessment of sympathetically controlled sudomotor function, and is based on a reaction between electrodes and chloride ions after a low-voltage sweat gland stimulation as the patient is situated with their hands and feet on two different measure pads for 3 minutes.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Pain tolerability: Cold pressor test
The left hand is immersed in circulated ice-chilled water (2.0°C). The subject will be instructed to tolerate to hold the hand in the water for up to 120 seconds or when intolerable pain is reached. At different timepoints throughout the stimulation, the participants are asked to rate the sensation on a numerical rating scale from 0 to 10, where 0 = no pain and 10 = worst pain.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Pain tolerability: Conditioned pain modulation (CMP)
The CPM-capacity response can be quantified by applying a "test-pain" (muscle pressure on right quadriceps) before and after the conditioning stimulus. The difference in pressure stimulus intensity before, during, and after induction of cold pressor pain provides a quantitative index of CPM capacity in the individual participant. The techniques used for pressure stimulation and cold pressor test described above will be combined to measure CPM.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Cardiac function
Cardiac function is assessed with echocardiography, which is a non-invasive ultrasound examination elapsing from 15 -30 minutes, performed with the patient in supine position. A transducer is run across the thorax for visualization of cardiac diastolic and systolic function, anatomical structures, arterial stiffness as well as muscle and chamber sizes to describe systolic and diastolic cardiac function.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Vascular function: Microvascular function
Nailfold video capillaroscopy is a non-invasive diagnostic technique that evaluates the morphology of the capillaries in the nailfold through direct visualization. It can reveal both the architecture of capillary rows and fine details of each vessel.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE routine status
SLE clinical status is assessed by performing routine blood-based analyses of hematological, serological and urinary markers for different organ-specific and SLE-specific characteristics.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE inflammatory status - Multiplex plasma cytokine analysis
SLE inflammatory status is assessed by analyzing the blood plasma for especially activation markers: TNF, IL-1b, sIL-2Ra, IL-6, IL-8, IL-17, IFN-g, IFN-alfa and Inhibition markers: sTNFr, IL-1RA, IL-10, TGF-b.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE inflammatory status - Interferon-regulated gene expression
SLE inflammatory status is assessed by analyzing interferon-regulated gene expression in whole blood (nCounter platform, NanoString Technologies, Seattle, WA).
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE inflammatory status - Immune cell population distribution in whole blood
SLE inflammatory status is assessed by analyzing the immune cell population distribution in whole blood (fluorescence-activated cell sorting).
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE inflammatory status - Functional immune cell stimulation
SLE inflammatory status is assessed by analyzing immune cell stimulation in whole blood (TruCulture).
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Kidney function
Kidney function is assessed by analyzing urine (3*24 hours) for kidney specific markers such as urine albumin- and protein/creatinine-ratio.
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Metabolic control
Metabolic control is assessed at the hospital by analyzing blood plasma for lipid and glucose profiles
Measured: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Medication usage
Changes in medication status within the time frame of the study and 3 months after study completion is recorded by accessing the participants medication file.
Measured: Medication status is reported at all visits (period 1: baseline and follow-up (day 7); period 2: baseline, day 7 and follow-up (week 8)) and three months after completing the study

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

24 Aug 202223 Aug 2023

First posted7 Apr 2022
Study start24 Aug 2022
Primary completion23 Aug 2023
Study completion23 Aug 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Systemic Lupus ErythematosusStudies of the same condition, open and under way.
More trials run by Copenhagen University Hospital, RigshospitaletThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 75 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05315739
Sponsor's protocol ID: SLE-VNS-1.0
Acronym: SLE-VNS
Status last verified: Sep 2025
First submitted: 25 Feb 2022
Last updated: 26 Sep 2025
Results posted: No
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: Yes
Individual data sharing: Yes: Data can be provided upon request.

Publications

Zinglersen AH, Drange IL, Myhr KA, Fuchs A, Pfeiffer-Jensen M, Brock C, Jacobsen S. Vagus nerve stimulation as a novel treatment for systemic lupus erythematous: study protocol for a randomised, parallel-group, sham-controlled investigator-initiated clinical trial, the SLE-VNS study. BMJ Open. 2022 Sep 20;12(9):e064552. doi: 10.1136/bmjopen-2022-064552.
PubMed 36127117

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Systemic Lupus Erythematosus trials

Study at a glance

From the registry record, last updated by the sponsor on 26 Sep 2025. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Vagus Nerve Stimulation as a Novel Treatment for Systemic Lupus Erythematous: A Double Blinded Randomized Controlled Trail
ClinicalTrials.gov ID: NCT05315739
Acronym / sponsor ID: SLE-VNS / SLE-VNS-1.0
Conditions: Systemic Lupus Erythematosus, Autonomic Dysfunction, Autonomic Neuropathy, Fatigue
Keywords: Vagus Nerve Stimulation, Fatigue, Pain, Health-Related Quality Of Life, Autonomic Nervous System Disorders, Inflammation, Autoimmunity, Kidney Diseases
Study type: Interventional
Recruitment status: Completed
Enrolment: 75 participants (actual)
Lead sponsor: Copenhagen University Hospital, RigshospitaletUniversity, hospital or other
Collaborators: Aalborg University Hospital
Study start: 24 Aug 2022 (actual)
Primary completion: 23 Aug 2023 (actual)
Study completion: 23 Aug 2023 (actual)
First posted: 7 Apr 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Active treatment	Active comparator	Device: Non-invasive transcutaneous vagus nerve stimulation (tVNS)Non-invasive transcutaneous vagus nerve stimulation applied by the gammaCore device (electroCore)
Sham treatment	Sham comparator	Device: Sham vagus nerve stimulationInactive sham vagus nerve stimulation applied by the gammaCore sham device (electroCore)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (12 listed)

Reading and understanding Danish.
SLE diagnosis based on SLE disease classification criteria for at least 1 year.
Stable disease and medication the past 28 days as defined by:
Having signs of fatigue, as assessed by scoring ≤ 40 in the FACIT-Fatigue questionnaire.
Having signs of autonomic dysfunction, as assessed by scoring one or more of:

Key exclusion criteria (16 listed)

Significant cardiovascular disease, including congenital cardiac disease, congestive heart failure, known severe coronary artery disease, or recent myocardial infarction (within 5 years), as assessed by a physician at the screening.
Blood pressure < 100/60 or > 160/105
Clinically significant bradycardia or tachycardia
History of abnormal baseline ECG, prolonged QT interval or arrhythmia
Previous surgery on the vagus nerve or abnormal cervical anatomy

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Non-invasive transcutaneous vagus nerve stimulation (tVNS)Also: GammaCore Sapphire devicetVNS delivers an electrical current to the cervical branch of the vagus nerve. Four minutes of bilateral stimulation 4 times per day for 7 days (period 1) and 2 times per day for 8 weeks (period 2) are performed. The two periods are separated by a 2 weeks wash-out period.	Device	Active treatment
Sham vagus nerve stimulationAlso: GammaCore Sapphire sham deviceThe sham device produces a slight vibrating sound, but does not produce an electical current and hence, does not activate the vagus nerve. Four minutes of bilateral stimulation 4 times per day for 7 days (period 1) and 2 times per day for 8 weeks (period 2). The two periods are separated by a 2 weeks wash-out period.	Device	Sham treatment

Primary outcome

Fatigue (changes during period 1 and 2)
Time frame: During period 1: At baseline, daily (day 2-6) until- and at follow-up (day 7). During period 2: At baseline, at day 7-visit, weekly (week 3-7) until- and at follow-up (week 8).
The FACIT-Fatigue Scale is a short, 13-item, tool that measures an individual's level of fatigue during their usual daily activities over the past week. The level of fatigue is measured on a four-point scale for each item. The theoretical maximum value is 52 (maximal fatigue) and minimum 0 (no fatigue).

28 secondary outcomes

Questionnaire on autonomic symptoms: Composite Autonomic Symptoms Score 31 (COMPASS-31)
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Questionnaire on SLE disease activity: Patient Global Assessment (PtGA)
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit, weekly (week 3-7) until- and at follow-up (week 8).
Questionnaire on SLE disease activity: Systemic Lupus Activity Questionnaire (SLAQ)
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit, and at follow-up (week 8).
Questionnaire on quality of life: Short form-12 (SF-12)
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit, and at follow-up (week 8).
Questionnaire on pain: Visual analog rating scale (VAS)
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit, weekly (week 3-7) until- and at follow-up (week 8).
SLE disease activity: SLE Disease Activity Index 2000 (SLEDAI-2K)
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE disease activity: SLEDAI Responder Index 50% (SRI-50)
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE disease activity: SLE Disease Activity Score (SLE-DAS)
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE disease activity: Physician Global Assessment (PGA)
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE disease activity: Painful and swollen joints
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Autonomic function: Resting heart rate variability (HRV)
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Autonomic function: Resting Cardiac Vagal Tone (CVT)
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Autonomic function: Cardiovascular autonomic reflex tests - heart rate response
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Autonomic function: Cardiovascular autonomic reflex tests - blood pressure response
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Autonomic function: Continuous heart rate and HRV monitoring
Time frame: During period 1: From baseline to follow-up (day 7). During period 2: From baseline to day 7-visit.
Autonomic function: Sweat secretion
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Pain tolerability: Cold pressor test
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Pain tolerability: Conditioned pain modulation (CMP)
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Cardiac function
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Vascular function: Microvascular function
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE routine status
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE inflammatory status - Multiplex plasma cytokine analysis
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE inflammatory status - Interferon-regulated gene expression
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE inflammatory status - Immune cell population distribution in whole blood
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
SLE inflammatory status - Functional immune cell stimulation
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Kidney function
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Metabolic control
Time frame: During period 1: At baseline and follow-up (day 7). During period 2: At baseline, at day 7-visit and at follow-up (week 8).
Medication usage
Time frame: Medication status is reported at all visits (period 1: baseline and follow-up (day 7); period 2: baseline, day 7 and follow-up (week 8)) and three months after completing the study

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 26 Sep 2025.
Derived from this study: PubMed 36127117Zinglersen AH, Drange IL, Myhr KA, Fuchs A, Pfeiffer-Jensen M, Brock C, Jacobsen S. Vagus nerve stimulation as a novel treatment for systemic lupus erythematous: study protocol for a randomised, parallel-group, sham-controlled investigator-initiated clinical trial, the SLE-VNS study. BMJ Open. 2022 Sep 20;12(9):e064552. doi: 10.1136/bmjopen-2022-064552.
Individual participant dataSharing planned: Yes. Data can be provided upon request.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Søren H Jacobsen, DMSc principal investigator

Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 12 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 26 Sep 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Fatigue (changes during period 1 and 2) (time frame: During period 1: At baseline, daily (day 2-6) until- and at follow-up (day 7). During period 2: At baseline, at day 7-visit, weekly (week 3-7) until- and at follow-up (week 8).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05315739, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Sep 2025.