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

Northwell Health19 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

Conditions

Lupus Erythematosus, Systemic Musculoskeletal Pain

Interventions

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.

Sham vagus nerve stimulationDEVICE

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.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: 1. Age ≥18 years, 2. SLE (defined by the ACR or SLICC criteria), 3. Musculoskeletal pain ≥ 4 on a non-anchored VAS 10 cm scale 4. BILAG C on Musculoskeletal Domain of the BILAG 2004 5. If on corticosteroids, the dose must be stable and ≤ 10mg/day (prednisone or equivalent) for at least 28 days before baseline, 6. If on background immunosuppressive treatment the dose must be stable for at least 28 days before baseline 7. Able and willing to give written informed consent and comply with the requirements of the study protocol. Exclusion Criteria: 1. Treatment with rituximab within one year of baseline (subjects with previous treatment with rituximab can enter study only with documentation of B cell repletion), 2. Treatment with cyclophosphamide within 2 months of baseline, 3. Expectation to increase steroids and/or immunosuppressive treatment, 4. Anti-phospholipid syndrome, 5. Fibromyalgia (fibromyalgia will be defined as a score \> 13 on the Fibromyalgia Symptom Scale (FSS). 6. Treatment with an anti-cholinergic medication, including over the counter medications, 7. Implantable electronic devices such as pacemakers, defibrillators, hearing aids, cochlear implants or deep brain stimulators. 8. Current tobacco or nicotine user, 9. Joint replacement within 60 days prior to study enrollment or planned within the course of the study, 10. Any planned surgical procedure requiring general anesthesia within the course of the study, 11. Intra-articular cortisone injections within 28 days of the start of study, 12. Chronic inflammatory disorders apart from SLE affecting the joints, 13. 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, 14. Active infection including hepatitis B or hepatitis C at baseline, 15. Any condition which, in the opinion of the investigator, would jeopardize the subject's safety following exposure to a study intervention, 16. Pregnancy or lactation, 17. Comorbid disease that may require administration of corticosteroid use, 18. Inability to comply with study and follow-up procedures.

Outcomes

Primary Outcomes

Change in Musculoskeletal Pain From Baseline.

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.

Time frame: 5 days

Percentage of Subjects With Treatment Emergent Adverse Events.

The percentage of participants with grade 2 or higher treatment emergent adverse events will be assessed using the NCI-CTAEversion4.

Time frame: 12 days

Secondary Outcomes

Change in Musculoskeletal Pain From Baseline

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.

Time frame: 12 days

Fatigue

Change from baseline fatigue will be measured using the FACIT F (Functional Assessment of Chronic Illness Therapy) questionnaire. The score ranges from 0 to 52, a higher score indicates less fatigue.

Time frame: 5 days

Fatigue

Change from baseline fatigue will be measured using the FACIT F (Functional Assessment of Chronic Illness Therapy) questionnaire. The score ranges from 0 to 52, a higher score indicates less fatigue.

Time frame: 12 days

Tender Joint Reduction

The percentage of tender joints reduced from baseline assessed by an investigator upon examining 68 potential tender joints.

Time frame: 5 days

Tender Joint Reduction

The percentage of tender joints reduced from baseline assessed by an investigator upon examining 68 potential tender joints.

Time frame: 12 days

Swollen Joint Count Reduction

The percentage of swollen joints reduced from baseline assessed by an investigator upon examining 66 potential swollen joints. Data shown for seven taVNS and five SS subjects with swollen joints at baseline.

Time frame: 5 days

Swollen Joint Count Reduction

Time frame: 12 days

Physician Global Assessment of Disease Activity (PGA)

Change in PGA from baseline, an anchored visual analog scale.ranging from 0 to 3 with higher scores signifying higher disease activity.

Time frame: 5 days

Physician Global Assessment of Disease Activity (PGA)

Change in PGA from baseline, an anchored visual analog scale.ranging from 0 to 3 with higher scores signifying higher disease activity.

Time frame: 12 days

Patient Global Assessment of Disease (PtGA)

Change in Patient Global Assessment of disease (PtGA) from baseline. This measure is a 10 cm visual analog scale (0-10); higher scores indicate a higher patient assessment of their disease activity.

Time frame: 5 days

Patient Global Assessment of Disease (PtGA)

Change in Patient Global Assessment of disease (PtGA) from baseline. This measure is a 10 cm visual analog scale (0-10); higher scores indicate a higher patient assessment of their disease activity.

Time frame: 12 days

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes