Transcutaneous Vagus Nerve Stimulation for the Treatment of Lupus
Condition: Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Intervention: TENS for vagus stimulation; TENS for sham stimulation
Intervention description: TENS electrodes are applied on an area of the external ear innervated by the auricular branch of the vagus nerve.; TENS electrodes are applied on an area of the external ear devoid of vagus innervation.
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 7.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: vagus nerve stimulation; systemic lupus erythematosus

Summary:

      This is a 3-month double blinded randomized controlled study of transcutaneous electrical
      vagus nerve stimulation (tVNS) compared to a sham stimulation for the treatment of patients
      with active systemic lupus erythematosus (SLE).
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patients with SLE age 18-70 meeting the American College of Rheumatology
             Classification Criteria. Patients need to meet a minimum of 4 out of 11 criteria
             simultaneously or serially on two separate occasions.

          2. Positive antinuclear antibody or anti-dsDNA within one year of screening

          3. Non-serological SLEDAI ≥4 or ≥1 BILAG B or A and presence of inflammatory arthritis
             (defined by at least 3 swollen and 3 tender joints) at screening

          4. Patients may receive on one or more of the following immune suppressive therapies:
             hydroxychloroquine, quinacrine, methotrexate, azathioprine, mycophenolate mofetil,
             tacrolimus, sirolimus, belimumab, abatacept. Immune suppressive medications should
             have been administered at stable doses for ≥30 days prior to baseline. Patients may
             also be on prednisone up to 10mg daily or equivalent steroid treatment at the baseline
             visit.

        Exclusion Criteria:

          1. Acute lupus nephritis defined as class II,III, IV or V nephritis diagnosed within 6
             months or prot/creat > 1.5 gm/gm due to active lupus or in process of receiving
             induction therapy for nephritis

          2. Active CNS lupus affecting mental status

          3. Any other organ threatening or life threatening manifestation of SLE as well as those,
             who, in the opinion of the investigator, have severe multi-organ or refractory lupus

          4. Rituximab treatment within 6 months prior to screening and/or without return of B
             cells to baseline levels

          5. Treatment with cyclophosphamide within a month prior to screening

          6. Treatment with any investigational drug within 3 months or 5 half-lives whichever is
             longer

          7. Recurrent vaso-vagal syncopal episodes

          8. Unilateral or bilateral vagotomy

          9. Presence of any evidence of vagus nerve pathology or injury

         10. Heart failure (NYHA class III or IV)

         11. Known atherosclerotic disease, including severe carotid artery disease, uncontrolled
             hypertension, uncontrolled diabetes, and history of myocardial infarction (MI),
             cardiomyopathy or stroke within the past year. Clinically stable patients with
             coronary artery disease, but no recent MI (within the past year) and no current
             symptoms of angina are not however excluded.

         12. Valvular and other structural heart disease that is evident by transthoracic
             echocardiogram and is associated with heart failure (NYHA class III or IV)

         13. Prolonged QT interval or abnormal baseline ECG - sick sinus syndrome, Mobitz type 2
             second or third degree heart block, atrial fibrillation, atrial flutter, recent
             history of ventricular tachycardia or ventricular fibrillation or clinically
             significant premature ventricular contraction

         14. Individuals currently implanted with an electrical and/or neurostimulator device, such
             as cardiac pacemaker or defibrillator, vagal neurostimulator, deep brain stimulator,
             spinal stimulator, bone growth stimulator, or cochlear implant

         15. Known respiratory disease that has decreased any pulmonary function test more than 25%
             below expected values or has resulted in hospitalization within the past year

         16. All diagnosed syndromes affecting the central nervous system (CNS) or autonomic
             nervous system

         17. Major psychiatric disorders including evidence of major depressive disorder (DSM-5
             diagnostic criteria) that is not currently controlled by medications

         18. Hemoglobin below 9.0 gm/dL (by the most recent CBC)

         19. Pregnancy or breast feeding

         20. Inability or unwillingness to understand and/or sign informed consent

         21. Any other medical condition, whether or not related to lupus, which, in the opinion of
             the investigator, would render the patient inappropriate or too unstable to complete
             the study protocol