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

Musculoskeletal Pain Clinical Trial

Official title:

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

Clinical Trial Details — Status: Enrolling by invitation

Administrative data

• NCT number: NCT02822989
• Other study ID #: 16-0171
• Status: Enrolling by invitation
• Phase: N/A
• Start date: November 1, 2017
• Est. completion date: November 1, 2020

Study information

• Verified date: September 2020
• Source: Northwell Health
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Enrolling by invitation
• Enrollment: 18
• Est. completion date: November 1, 2020
• Est. primary completion date: April 30, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Lupus Erythematosus, Systemic
• Musculoskeletal Pain

Intervention

Device:
• 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.
• 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.

Locations

Country	Name	City	State
United States	Feinstein Institute	Manhasset	New York

Sponsors (2)

Lead Sponsor	Collaborator
Northwell Health	John and Marcia Goldman Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	TNF, HMGB1, IL-6, Il1B, IFNa and IL10 levels	Levels of inflammatory cytokines (ie TNF, HMGB1, IL-6, Il1B, IFNa and IL10) will be measured in patients sera.	5 days
Other	TNF, HMGB1, IL-6, Il1B, IFNa and IL10 levels	Levels of inflammatory cytokines (ie TNF, HMGB1, IL-6, Il1B, IFNa and IL10) will be measured in patients sera.	12 days
Other	Lipopolysaccharide stimulated levels of TNF, HMGB1, IL-6, Il1B, IFNa and IL10 in whole blood.	Whole blood will be taken from patients and stimulated by lipopolysaccharide. Levels of TNF, HMGB1, IL-6, Il1B, IFNa and IL10 that are produced by the cells in the whole blood will be measured.	5 days
Other	Lipopolysaccharide stimulated levels of TNF, IL-6, Il1B, IFNa and IL10 in whole blood.	Whole blood will be taken from patients and stimulated by lipopolysaccharide. Levels of TNF, HMGB1, IL-6, Il1B, IFNa and IL10 that are produced by the cells in the whole blood will be measured.	12 days
Other	Gardiquimod stimulated levels of TNF, IL-6, Il1B, IFNa and IL10 in whole blood.	Whole blood will be taken from patients and stimulated by gardiquimod.. Levels of TNF, HMGB1, IL-6, Il1B, IFNa and IL10 that are produced by the cells in the whole blood will be measured.	5 days
Other	Gardiquimod stimulated levels of TNF, IL-6, Il1B, IFNa and IL10 in whole blood.	Whole blood will be taken from patients and stimulated by gardiquimod.. Levels of TNF, HMGB1, IL-6, Il1B, IFNa and IL10 that are produced by the cells in the whole blood will be measured.	12 days
Other	CpG stimulated levels of TNF, IL-6, Il1B, IFNa and IL10 in whole blood.	Whole blood will be taken from patients and stimulated by CpG. Levels of TNF, HMGB1, IL-6, Il1B, IFNa and IL10 that are produced by the cells in the whole blood will be measured.	5 days
Primary	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	SLE Disease activity	SLE disease activity will be assessed using the SLEDAI, a validated disease activity instrument for SLE.	5 days
Secondary	Fatigue	Fatigue will be measured using the FACET F questionnaire which will be completed by each subject.	5 days
Secondary	Fatigue	Fatigue will be measured using the FACET F questionnaire which will be completed by each subject.	12 days
Secondary	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
Secondary	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
Secondary	SLE cutaneous activity	Cutaneous activity will be assessed using the CLASI, a validated index for SLE skin disease.	5 days
Secondary	SLE cutaneous activity	Cutaneous activity will be assessed using the CLASI, a validated index for SLE skin disease.	12 days
Secondary	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
Secondary	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