Clinical trial NCT02822989: Using the Cholinergic Anti-Inflammatory Pathway to Treat Systemic Lupus Musculoskeletal Pain
Official title: Using the Cholinergic Anit-Inflammatory Pathway to Treat Systemic Lupus Musculoskeletal Pain
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Lupus Erythematosus, Systemic
Musculoskeletal Pain
Keywords: Lupus Erythematosus, Systemic
Musculoskeletal Pain
Inflammation
Lead sponsor: Northwell Health
Sponsor class: OTHER
Collaborators: name: John and Marcia Goldman Foundation
First posted: 2016-07-06
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Musculoskeletal pain.
timeFrame: 5 days
Secondary outcomes:
measure: SLE Disease activity
timeFrame: 5 days
measure: Fatigue
timeFrame: 5 days
measure: Fatigue
timeFrame: 12 days
measure: Tender and swollen joint counts
timeFrame: 5 days
measure: Tender and swollen joint counts
timeFrame: 12 days
measure: SLE cutaneous activity
timeFrame: 5 days
measure: SLE cutaneous activity
timeFrame: 12 days
measure: Musculoskeletal Pain
timeFrame: 12 days
measure: Percentage of subjects with treatment emergent adverse events.
timeFrame: 12 days
Other outcomes:
measure: TNF, HMGB1, IL-6, Il1B, IFNα and IL10 levels
timeFrame: 5 days
measure: TNF, HMGB1, IL-6, Il1B, IFNα and IL10 levels
timeFrame: 12 days
measure: Lipopolysaccharide stimulated levels of TNF, HMGB1, IL-6, Il1B, IFNα and IL10 in whole blood.
timeFrame: 5 days
measure: Lipopolysaccharide stimulated levels of TNF, IL-6, Il1B, IFNα and IL10 in whole blood.
timeFrame: 12 days
measure: Gardiquimod stimulated levels of TNF, IL-6, Il1B, IFNα and IL10 in whole blood.
timeFrame: 5 days
measure: Gardiquimod stimulated levels of TNF, IL-6, Il1B, IFNα and IL10 in whole blood.
timeFrame: 12 days
measure: CpG stimulated levels of TNF, IL-6, Il1B, IFNα and IL10 in whole blood.
timeFrame: 5 days
Locations:
city: Manhasset
country: United States
facility: Feinstein Institute
state: New York
Study officials:
affiliation: Northwell Health
name: Cynthia Aranow, M.D.
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.