Overview
This two-stage, multicenter clinical trial is designed to evaluate the feasibility, safety, and preliminary efficacy of at-home ultrasound stimulation to activate immune-neuromodulation in patients with rheumatoid arthritis (RA) and at least moderate disease activity. The study will enroll up to 40 participants at up to 6 sites across 2 stages. 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 for a daily home-use therapy.
Description
Stage 1 is an open-label pilot study of 5-8 participants receiving active daily ultrasound stimulation for 8 weeks. The primary objective is to assess feasibility and safety, defined by the absence of device-related serious adverse events (SAEs) or Grade ≥2 adverse events (AEs) requiring medical intervention per CTCAE criteria. Data from Stage 1 will be used to refine trial procedures and confirm readiness for Stage 2.
Stage 2 consists of a randomized double-blind, sham-controlled study enrolling up to 30 participants, allocated 2:1 to receive active or sham daily ultrasound stimulation for 8 weeks. This stage is designed to estimate the treatment effect size, using clinical and biomarker-based endpoints, and to collect safety and adherence data on a larger cohort.
All participants will be followed through Week 12 to assess post-treatment safety and durability of clinical and immunologic effects.
Eligibility
Inclusion Criteria:
- At least 18 years old
- Diagnosis of rheumatoid arthritis as defined by ACR/EULAR 2010 classification criteria
- A positive test result for Rheumatoid Factor (RF) \> 14 IU/mL and/or Anti-Citrullinated Protein Antibodies (Anti-CCP) ≥ 20 U/mL
- At least moderate disease activity, defined as DAS28-CRP \> 3.8 and at least 4/28 tender and 4/28 swollen joints at the screening and baseline visits
- High sensitivity CRP (hsCRP) ≥ 10 mg/L at the screening and baseline visits
- On stable dose of background DMARD therapy (see exclusion criteria)
- Able and willing to comply with all study-related procedures, including at-home device use, daily treatment, scheduled visits, and assessments
Exclusion Criteria:
- Unable to provide informed consent
- Current or planned participation in another interventional clinical trial
- Prior use of \> 2 biologic or targeted synthetic DMARDs for RA where the primary reason for discontinuation was efficacy
- Conventional synthetic DMARDs:
- Initiated within last 12 weeks or adjusted dose within 4 weeks prior to enrollment
- Inability to maintain a stable dose during the study
- Biologic DMARDs:
- Initiated or dose-adjusted within 12 weeks prior to enrollment
- Inability to maintain a stable dose during the study
- JAK inhibitors:
- Use within 4 weeks prior to enrollment or expected use during study participation
- Corticosteroids:
- Initiated or dose-adjusted within 4 weeks prior to enrollment
- Current dose \> 10 mg/day prednisone (or equivalent)
- Current tobacco or nicotine product use
- Pregnant or planning to become pregnant during the study period
- Known hypersensitivity to ultrasound gel or membrane components
- Active bacterial, viral, or fungal infection
- Receiving chemotherapy or immunotherapy for malignancy
- History of splenic disorders, including splenectomy, congenital asplenia, or splenomegaly on screening 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
- Uncontrolled fibromyalgia or other diffuse pain syndromes that may confound symptom reporting