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

NCT ID: NCT02822989

Last Updated: 2020-09-09

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2017-11-01
• Study Completion Date: 2020-11-01

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.

Conditions

Lupus Erythematosus, Systemic; Musculoskeletal Pain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Vagus Nerve Stimulation

Subjects randomized to this arm will receive transcutaneous vagus nerve stimulation for 5 minutes on 4 consecutive days.

Group Type: ACTIVE_COMPARATOR

Vagus nerve stimulation

Intervention Type: DEVICE

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 Stimulation

Subjects randomized to this arm will receive sham stimulation for 5 minutes for 4 consecutive days.

Group Type: SHAM_COMPARATOR

Sham vagus nerve stimulation

Intervention Type: DEVICE

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.

Interventions

Vagus nerve stimulation

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.

Intervention Type: DEVICE

Sham vagus nerve stimulation

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.

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

John and Marcia Goldman Foundation

UNKNOWN

Sponsor Role: collaborator

Northwell Health

OTHER

Sponsor Role: lead

Responsible Party

Cynthia Aranow, MD

Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Cynthia Aranow, M.D.

Role: PRINCIPAL_INVESTIGATOR

Northwell Health

Locations

Feinstein Institute

Manhasset, New York, United States

Countries

United States

References

Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.

Reference Type: DERIVED

PMID: 33687069 (View on PubMed)

Other Identifiers

16-0171

Identifier Type: -

Identifier Source: org_study_id