Ultrasound Neuroimmune Modulation in Adults With Rheumatoid Arthritis

This two-stage, multicenter clinical trial is designed to evaluate the feasibility, safety, and preliminary efficacy of splenic ultrasound stimulation to activate immune-neuromodulation (SUSTAIN) in patients with rheumatoid arthritis (RA) and at least moderate disease activity. The findings from this trial will directly inform the design and power calculations for a future pivotal trial by identifying an appropriate effect size and confirming protocol feasibility and safety.

Inclusion Criteria: * 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 Exclusion Criteria: * Unable to provide informed consent * Current or planned participation in another interventional clinical trial * 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. * 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 * 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 * 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 * Recent abdominal surgery or trauma within 30 days of screening * Skin to spleen hilum depth \>7 cm as measured by ultrasound at the baseline visit * 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