Vagus Nerve Stimulation for Systemic Lupus Erythematous

NCT05315739 | Completed FDA Device

• 1 other identifier: SLE-VNS-1.0
• Study Type: interventional
• Target: 75
• Locations: 1 country
• Sites: 1

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

Keywords

Vagus Nerve Stimulation; Fatigue; Pain; Health-Related Quality Of Life; Autonomic Nervous System Disorders; Inflammation; Autoimmunity; Kidney Diseases; Vascular Diseases; Heart Diseases

Outcome Measures

Primary Outcomes (1)

• 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).

  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)

  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)

  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)

  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)

  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)

  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).

Study Arms (2)

Active treatment

ACTIVE COMPARATOR

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

Device: Non-invasive transcutaneous vagus nerve stimulation (tVNS)

Sham treatment

SHAM COMPARATOR

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

Device: Sham vagus nerve stimulation

Interventions

Non-invasive transcutaneous vagus nerve stimulation (tVNS) 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.

Also known as: GammaCore Sapphire device

Active treatment

Sham vagus nerve stimulation 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.

Also known as: GammaCore Sapphire sham device

Sham treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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.
• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Aalborg University Hospital: collaborator

Study Sites (1)

Rigshospitalet

Copenhagen, 2100, Denmark

Location

Related Publications (1)

• 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.

  PMID: 36127117 DERIVED

MeSH Terms

Conditions

Lupus Erythematosus, Systemic; Primary Dysautonomias; Fatigue; Pain; Autonomic Nervous System Diseases; Inflammation; Autoimmune Diseases; Kidney Diseases; Vascular Diseases; Heart Diseases

Condition Hierarchy (Ancestors)

Connective Tissue Diseases; Skin and Connective Tissue Diseases; Immune System Diseases; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurologic Manifestations; Pathologic Processes; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Cardiovascular Diseases

Study Officials

• Søren H Jacobsen, DMSc

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, MD, DMSc

Study Record Dates

• First Submitted: February 25, 2022
• First Posted: April 7, 2022
• Study Start: August 24, 2022
• Primary Completion: August 23, 2023
• Study Completion: August 23, 2023
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Time Frame: From study end.
• Access Criteria: Researchers who provide a methodological sound proposal

Locations

DK (1)