Clinical trial NCT05315739: Vagus Nerve Stimulation for Systemic Lupus Erythematous
Official title: Vagus Nerve Stimulation as a Novel Treatment for Systemic Lupus Erythematous: A Double Blinded Randomized Controlled Trail
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
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
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: Aalborg University Hospital
First posted: 2022-04-07
Enrollment: 84
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Fatigue (changes during period 1 and 2)
timeFrame: 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:
measure: Questionnaire on autonomic symptoms: Composite Autonomic Symptoms Score 31 (COMPASS-31)
timeFrame: 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).
measure: Questionnaire on SLE disease activity: Patient Global Assessment (PtGA)
timeFrame: 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).
measure: Questionnaire on SLE disease activity: Systemic Lupus Activity Questionnaire (SLAQ)
timeFrame: 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).
measure: Questionnaire on quality of life: Short form-12 (SF-12)
timeFrame: 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).
measure: Questionnaire on pain: Visual analog rating scale (VAS)
timeFrame: 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).
measure: SLE disease activity: SLE Disease Activity Index 2000 (SLEDAI-2K)
timeFrame: 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).
measure: SLE disease activity: SLEDAI Responder Index 50% (SRI-50)
timeFrame: 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).
measure: SLE disease activity: SLE Disease Activity Score (SLE-DAS)
timeFrame: 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).
measure: SLE disease activity: Physician Global Assessment (PGA)
timeFrame: 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).
measure: SLE disease activity: Painful and swollen joints
timeFrame: 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).
measure: Autonomic function: Resting heart rate variability (HRV)
timeFrame: 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).
measure: Autonomic function: Resting Cardiac Vagal Tone (CVT)
timeFrame: 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).
measure: Autonomic function: Cardiovascular autonomic reflex tests - heart rate response
timeFrame: 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).
measure: Autonomic function: Cardiovascular autonomic reflex tests - blood pressure response
timeFrame: 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).
measure: Autonomic function: Continuous heart rate and HRV monitoring
timeFrame: During period 1: From baseline to follow-up (day 7). During period 2: From baseline to day 7-visit.
measure: Autonomic function: Sweat secretion
timeFrame: 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).
measure: Pain tolerability: Cold pressor test
timeFrame: 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).
measure: Pain tolerability: Conditioned pain modulation (CMP)
timeFrame: 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).
measure: Cardiac function
timeFrame: 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).
measure: Vascular function: Microvascular function
timeFrame: 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).
measure: SLE routine status
timeFrame: 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).
measure: SLE inflammatory status - Multiplex plasma cytokine analysis
timeFrame: 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).
measure: SLE inflammatory status - Interferon-regulated gene expression
timeFrame: 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).
measure: SLE inflammatory status - Immune cell population distribution in whole blood
timeFrame: 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).
measure: SLE inflammatory status - Functional immune cell stimulation
timeFrame: 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).
measure: Kidney function
timeFrame: 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).
measure: Metabolic control
timeFrame: 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).
measure: Medication usage
timeFrame: 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
Other outcomes:
Locations:
Study officials:
affiliation: Rigshospitalet, Denmark
name: Søren Jacobsen, DMSc
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.