Using the Cholinergic Anti-Inflammatory Pathway to Treat Systemic Lupus Musculoskeletal Pain

Study Overview
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Brief Summary
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Systemic Lupus Erythematosus (SLE) is a chronic autoimmune, inflammatory disease and musculoskeletal pain is one of the most common symptoms. This study will investigate whether transcutaneous stimulation of the vagus nerve will decrease lupus musculoskeletal pain. This study will additionally investigate the biologic effects of vagus nerve stimulation on inflammation. It will be the first clinical study using one of the body's own pathways of modulating the immune system and inflammatory response, the cholinergic anti-inflammatory pathway, in SLE.

Official Title
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Using the Cholinergic Anit-Inflammatory Pathway to Treat Systemic Lupus Musculoskeletal Pain

Conditions
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Lupus Erythematosus, Systemic, Musculoskeletal Pain

Intervention / Treatment
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* Device: Vagus nerve stimulation
* Device: Sham vagus nerve stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years, SLE (defined by the ACR 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 or equivalent) for at least 28 days before baseline, If on background immunosuppressive treatment the dose must be stable for at least 28 days before baseline Able and willing to give written informed consent and comply with the requirements of the study protocol. Exclusion Criteria: Treatment with rituximab within one year of baseline (subjects with previous treatment with rituximab can enter study only with documentation of B cell repletion), Treatment with cyclophosphamide within 2 months of baseline, Expectation to increase steroids and/or immunosuppressive treatment, Anti-phospholipid syndrome, Fibromyalgia (fibromyalgia will be defined as a score > 13 on the Fibromyalgia Symptom Scale (FSS). Treatment with an anti-cholinergic medication, including over the counter medications, Implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators. Current tobacco or nicotine user, Joint replacement within 60 days prior to study enrollment or planned within the course of the study, Any planned surgical procedure requiring general anesthesia within the course of the study, 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 the investigational drug prior to the start of study drug dosing (Day 0), whichever is the greater length of time, Active infection including hepatitis B or hepatitis C at baseline, Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to a study intervention, Pregnancy or lactation, Comorbid disease that may require administration of corticosteroid use, Inability to comply with study and follow-up procedures.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Vagus Nerve Stimulation<br>Subjects randomized to this arm will receive transcutaneous vagus nerve stimulation for 5 minutes on 4 consecutive days. | Device: Vagus nerve stimulation<br>* Patients will receive transcutaneous stimulation of the auricular branch of the left vagus nerve for 5 minutes daily for 4 consecutive days. The device is a handheld electrical pulse generator and a pair of electrodes to be placed at the ear for stimulation. The specific target at the ear will be the auricular branch of the vagus nerve which innervates the skin of the ear canal. Electrodes will be placed near/at the entrance to the canal of the ear to provide stimulation to the auricular branch.<br>|
| Sham Comparator: Sham Vagus Nerve Stimulation<br>Subjects randomized to this arm will receive sham stimulation for 5 minutes for 4 consecutive days. | Device: Sham vagus nerve stimulation<br>* Patients will receive sham transcutaneous stimulation of the auricular branch of the left vagus nerve for 5 minutes daily for 4 consecutive days. Sham stimulation will be performed in the identical manner as true transcutaneous stimulation except that the patient will not receive electrical stimulation of the vagus nerve.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Musculoskeletal pain. | Patients rate their musculoskeletal pain by making a mark on a 10cm anchored Visual Analog Scale where 0=no musculoskeletal pain and 10 =worst possible musculoskeletal pain. | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SLE Disease activity | SLE disease activity will be assessed using the SLEDAI, a validated disease activity instrument for SLE. | 5 days | 
| Fatigue | Fatigue will be measured using the FACET F questionnaire which will be completed by each subject. | 5 days | 
| Fatigue | Fatigue will be measured using the FACET F questionnaire which will be completed by each subject. | 12 days | 
| Tender and swollen joint counts | The number of tender and swollen joints of the subject will be assessed by the investigator who will examine 68 potential tender joints and 66 potential swollen joints. | 5 days | 
| Tender and swollen joint counts | The number of tender and swollen joints of the subject will be assessed by the investigator who will examine 68 potential tender joints and 66 potential swollen joints. | 12 days | 
| SLE cutaneous activity | Cutaneous activity will be assessed using the CLASI, a validated index for SLE skin disease. | 5 days | 
| SLE cutaneous activity | Cutaneous activity will be assessed using the CLASI, a validated index for SLE skin disease. | 12 days | 
| Musculoskeletal Pain | Patients rate their musculoskeletal pain by making a mark on a 10cm anchored Visual Analog Scale where 0=no musculoskeletal pain and 10 =worst possible musculoskeletal pain. | 12 days | 
| Percentage of subjects with treatment emergent adverse events. | The percentage of participants with treatment emergent adverse events will be assessed using the NCI-CTAEversion4. | 12 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lupus Erythematosus, Systemic, Musculoskeletal Pain, Inflammation