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

Not Applicable

• Conditions: Lupus Erythematosus, Systemic; Musculoskeletal Pain
• Interventions: Device: Vagus nerve stimulation; Device: Sham vagus nerve stimulation

• Registration Number: NCT02822989
• Lead Sponsor: Northwell Health

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2016-05-26
• Study First Submitted QC: 2016-07-05
• Study First Posted: 2016-07-06
• Study Start: 2017-11-01
• Primary Completion: 2018-04-30
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-08
• Last Update Posted: 2020-09-09
• Study Completion: 2020-11-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 18

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Vagus Nerve Stimulation	Vagus nerve stimulation	Subjects randomized to this arm will receive transcutaneous vagus nerve stimulation for 5 minutes on 4 consecutive days.
Sham Vagus Nerve Stimulation	Sham vagus nerve stimulation	Subjects randomized to this arm will receive sham stimulation for 5 minutes for 4 consecutive days.

Primary Outcome Measures

Name	Time	Method
Musculoskeletal pain.	5 days	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.

Secondary Outcome Measures

Name	Time	Method
SLE Disease activity	5 days	SLE disease activity will be assessed using the SLEDAI, a validated disease activity instrument for SLE.
Fatigue	12 days	Fatigue will be measured using the FACET F questionnaire which will be completed by each subject.
Tender and swollen joint counts	12 days	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.
SLE cutaneous activity	12 days	Cutaneous activity will be assessed using the CLASI, a validated index for SLE skin disease.
Musculoskeletal Pain	12 days	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.
Percentage of subjects with treatment emergent adverse events.	12 days	The percentage of participants with treatment emergent adverse events will be assessed using the NCI-CTAEversion4.

Trial Locations

Locations (1)

Feinstein Institute; 🇺🇸 Manhasset, New York, United States