Vagus Nerve Stimulation for Systemic Lupus Erythematous

NCT ID: NCT05315739

Last Updated: 2025-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-08-24
• Study Completion Date: 2023-08-23

Brief 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).

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Active treatment

Non-invasive transcutaneous vagus nerve stimulation applied by the gammaCore device (electroCore)

Group Type: ACTIVE_COMPARATOR

Non-invasive transcutaneous vagus nerve stimulation (tVNS)

Intervention Type: 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 treatment

Inactive sham vagus nerve stimulation applied by the gammaCore sham device (electroCore)

Group Type: SHAM_COMPARATOR

Sham vagus nerve stimulation

Intervention Type: 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.

Interventions

Non-invasive transcutaneous vagus nerve stimulation (tVNS)

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.

Intervention Type: DEVICE

Sham vagus nerve stimulation

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.

Intervention Type: DEVICE

Other Intervention Names

GammaCore Sapphire device; GammaCore Sapphire sham device

Eligibility Criteria

Inclusion Criteria

• 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.
• Having signs of autonomic dysfunction, as assessed by scoring one or more of:

1. VAGUS score ≥1

2. SUDOSCAN score < 50µS for hands or < 70µS for feet

3. 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

Exclusion Criteria

• 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
• 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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aalborg University Hospital

OTHER

Sponsor Role: collaborator

Rigshospitalet, Denmark

OTHER

Sponsor Role: lead

Responsible Party

Søren Jacobsen

Professor, MD, DMSc

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Søren H Jacobsen, DMSc

Role: PRINCIPAL_INVESTIGATOR

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

Locations

Rigshospitalet

Copenhagen, , Denmark

Countries

Denmark

References

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.

Reference Type: DERIVED

PMID: 36127117 (View on PubMed)

Other Identifiers

SLE-VNS-1.0

Identifier Type: -

Identifier Source: org_study_id