Ultrasound Neuroimmune Modulation in Adults With Rheumatoid Arthritis

Prior treatment

• Prior use of \>2 biologic or targeted synthetic DMARDs for RA where the primary reason for discontinuation was efficacy
• Conventional synthetic DMARDs:
  • Initiation within 12 weeks prior to enrollment
  • Dose adjustment or discontinuation within 4 weeks prior to enrollment
  • If on a stable dose, inability to maintain the stable dose during the study period
• Biologic DMARDs:
  • Initiation or dose adjustment within 12 weeks prior to enrollment
  • Discontinuation within 4 weeks prior to enrollment
  • If on a stable dose, inability to maintain the stable dose during the study period
• JAK inhibitors:
  • Initiation, dose adjustment, or discontinuation within 4 weeks prior to enrollment
  • If on a stable dose, inability to maintain the stable dose during the study period
• Corticosteroids:
  • Initiation, dose adjustment, or discontinuation within 4 weeks prior to enrollment
  • Current dose \>10 mg/day prednisone (or equivalent)
  • If on a stable dose, inability to maintain the stable dose during the study
• Recent abdominal surgery or trauma within 30 days of screening

Other illness

• Inflammatory joint disease other than RA (including but not limited to gout, systemic lupus erythematosus, psoriatic arthritis, axial spondyloarthritis including ankylosing spondylitis and non-radiographic axial spondyloarthritis, reactive arthritis, overlap connective tissue diseases, scleroderma, polymyositis, dermatomyositis. Current diagnosis of secondary Sjogren's Syndrome is permitted.
• Known hypersensitivity to ultrasound gel or membrane components
• History of splenic disorders, including splenectomy, congenital asplenia, or splenomegaly on baseline visit ultrasound
• Rash, wound, or skin infection overlying the spleen
• History of vagal nerve injury, vagotomy, or known autonomic neuropathy
• Abdominal anatomy or condition precluding adequate ultrasound targeting of the spleen
• Uncontrolled fibromyalgia or other diffuse pain syndromes that may confound symptom reporting
• Any condition that, in the investigator's judgment, would preclude safe participation or compliance with study procedures

Other

• Unable to provide informed consent
• Current or planned participation in another interventional clinical trial
• NSAIDs:
  • Initiation, dose adjustment, or discontinuation of high-dose NSAIDs (≥1200 mg/day ibuprofen) within 14 days of informed consent. Over-the-counter use of NSAIDs is permissible.
• Pregnant or planning to become pregnant during the study period
• Skin to spleen hilum depth \>7 cm as measured by ultrasound at the baseline visit

• At least 18 years old
• Diagnosis of rheumatoid arthritis as defined by ACR/EULAR 2010 classification criteria
• At least moderate disease activity, defined as ≥4 tender joints (28-joint count) and ≥4 swollen joints (28-joint count) and a DAS28-CRP \>3.2 at the baseline visit
• hsCRP \> 0.3 mg/dL at the last qualifying visit, baseline or retest
• If on background DMARD therapy, must be on stable dose (see exclusion criteria)
• Able and willing to comply with all study-related procedures, including daily treatment sessions in the study vehicle, research site visits, and assessments