Modelling and Control of Non-invasive Vagus Nerve Stimulation for Autoimmune Diseases (1A)

Inclusion Criteria:

• Systemic lupus erythematosus (SLE) (defined by the American College of Rheumatology-or SLICC criteria)
• Musculoskeletal pain ≥ 4 on a non-anchored VAS 10 cm scale
• BILAG C on Musculoskeletal Domain of the BILAG 2004
• If on corticosteroids, the dose must be stable and ≤ 10mg/day (prednisone orequivalent) for at least 28 days before baseline,
• If on background immunosuppressive treatment the dose must be stable for at least 28days before baseline
• Able and willing to give written informed consent and comply with the requirements ofthe study protocol.

Exclusion Criteria:

• Treatment with rituximab within one year of baseline as it is related to lymphocytedepletion that could alter the result of the biomarker study (subjects with previoustreatment with rituximab can enter study only with documentation of B cell repletion).
• Treatment with cyclophosphamide within 2 months of baseline as it is related tolymphocyte depletion that could alter the result of the biomarker study.
• Expectation to increase steroids and/or immunosuppressive treatment.
• Anti-phospholipid syndrome.
• Fibromyalgia (fibromyalgia will be defined as a score > 13 on the Fibromyalgia SymptomScale), chronic fatigue syndrome.
• Treatment with an anti-cholinergic or sympathicomimetic medication, including over thecounter medications.
• Implantable electronic devices such as pacemakers, defibrillators, hearing aids,cochlear implants or deep brain stimulators.
• Joint replacement within 60 days prior to study enrolment or planned within the courseof the study.
• Any planned surgical procedure requiring general anaesthesia within the course of thestudy.
• Intra-articular cortisone injections within 28 days of the start of study.
• Chronic inflammatory disorders apart from SLE affecting the joints.
• Investigational drug and/or treatment during the 28 days or seven half-lives of theinvestigational drug prior to the start of study drug dosing (Day 0), whichever is thegreater length of time.
• Active infection including hepatitis B, hepatitis C or HIV at baseline due to highprevalence of neuropathy.
• Any condition which, in the opinion of the investigator, would jeopardize thesubject's safety following exposure to a study intervention.
• Pregnancy or lactation.
• Haemoglobin below 9.0 gm/dL (by the most recent CBC) as anaemia is related to no-neurogenic orthostatic hypotension and increases cardiovascular symptoms in COMPASS 31scale
• Comorbid disease that may require administration of corticosteroid use.
• Inability to comply with study and follow-up procedures.
• Known cardiac arrhythmia, severe cardiac disease or neurodegenerative disease.
• Known or confirmed at baseline screening peripheral or autonomic nervous systeminvolvement, including LES-related, toxic polyneuropathies, metabolic neuropathies (including diabetes), etc.
• Previous experience with vagus nerve stimulation devices