Lupus Erythematosus, Systemic, Musculoskeletal Pain
Conditions
Keywords
Lupus Erythematosus, Systemic, Musculoskeletal Pain, Inflammation
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.
Interventions
DEVICEVagus 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.
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.
Sponsors
Northwell Health
John and Marcia Goldman Foundation
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Musculoskeletal Pain From Baseline. | 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. |
| Percentage of Subjects With Treatment Emergent Adverse Events. | 12 days | The percentage of participants with grade 2 or higher treatment emergent adverse events will be assessed using the NCI-CTAEversion4. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Musculoskeletal Pain From Baseline | 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. |
| Fatigue | 5 days | 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. |
| Tender Joint Reduction | 5 days | The percentage of tender joints reduced from baseline assessed by an investigator upon examining 68 potential tender joints. |
| Swollen Joint Count Reduction | 5 days | 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. |
| Physician Global Assessment of Disease Activity (PGA) | 5 days | Change in PGA from baseline, an anchored visual analog scale.ranging from 0 to 3 with higher scores signifying higher disease activity. |
| Patient Global Assessment of Disease (PtGA) | 5 days | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORCynthia Aranow, M.D.
Northwell Health
Participant flow
Recruitment details
Subjects were recruited from local clinics, word of mouth or from the ClinicalTrials.gov site.
Pre-assignment details
No subjects were excluded from the study before assignment to a treatment group.
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 48.5 years STANDARD_DEVIATION 12.9 |
| Fatigue | 23.0 units on a scale STANDARD_DEVIATION 9.1 |
| Pain | 6.7 cm STANDARD_DEVIATION 1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 4 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Region of Enrollment United States | 18 Participants |
| Sex: Female, Male Female | 12 Participants |
| Sex: Female, Male Male | 0 Participants |
| Swollen joints | 2 Swollen joints per subject STANDARD_DEVIATION 2.2 |
| Tender joints | 9.1 Tender joints per subject STANDARD_DEVIATION 8.8 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 13 | 0 / 6 |
| other Total, other adverse events | 1 / 13 | 0 / 6 |
| serious Total, serious adverse events | 0 / 13 | 0 / 6 |
Outcome results
None listed