Ultrasound Neuroimmune Modulation in Adults With Rheumatoid Arthritis (SUSTAIN)

July 2, 2026 updated by: Surf Therapeutics

Ultrasound Neuroimmune Modulation in Adults With Rheumatoid Arthritis: Feasibility and Safety in a Multicenter, Randomized, Double-Blind, Sham-Controlled Trial

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Stage 1 is an open-label pilot study of 6-10 participants. To maintain a seropositive-enriched cohort, enrollment of seronegative participants (those with RF ≤14 IU/mL and Anti-CCP <20 U/mL) is capped at 3 participants in Stage 1. All participants will receive daily active SUSTAIN therapy for 8 weeks. The initial active ultrasound parameter set (Experimental Treatment 1) will be based on the best available evidence at the start of the trial. If interim review of early efficacy data from the first 3-5 participants, specifically, the magnitude and direction of change in DAS28-CRP from Baseline to Week 4, suggests that a second parameter set may be warranted, the Sponsor may elect to enroll an additional 3-5 participants to receive a second active ultrasound parameter set (Experimental Treatment 2). This decision will be made by the Sponsor prior to enrollment of the first participant assigned to Experimental Treatment 2 and will be documented in a protocol decision memo. If the Sponsor determines that Experimental Treatment 1 demonstrates sufficient early signal, Stage 1 will be completed using a single parameter set.

The primary objective of Stage 1 is to assess feasibility, defined as ≥70% adherence to scheduled treatment sessions, 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 double-blind, randomized, sham-controlled study enrolling 30-40 participants, randomized 1:1 to receive daily active or sham SUSTAIN therapy for 8 weeks. Selection of the Stage 2 active treatment ultrasound parameter set will be based on the safety profile and magnitude/direction of the DAS28-CRP change from Baseline to Week 4 of the two experimental treatments. Enrollment of seronegative participants is capped at 10 in Stage 2, such that at least 75% of enrolled participants are seropositive. Randomization is stratified by serostatus to maintain balance across arms. This stage is designed to further characterize safety and adherence in a larger cohort, and to estimate treatment effect size using clinical and biomarker-based secondary endpoints.

All participants will be followed through Week 12 to assess post-treatment safety and durability of clinical and immunologic effects.

Study Type

Interventional

Enrollment (Estimated)

40

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Texas
      • Colleyville, Texas, United States, 75034
        • Recruiting
        • Precision Comprehensive Clinical Research Solutions
        • Principal Investigator:
          • Dhiman Basu, MD
        • Contact:
      • Dallas, Texas, United States, 75231
        • Recruiting
        • Rheumatology Associates
        • Contact:
        • Principal Investigator:
          • Robert Jenkins, MD, PhD
      • Irving, Texas, United States, 75061
        • Recruiting
        • Precision Comprehensive Clinical Research Solutions
        • Principal Investigator:
          • Renuka Basavaraju, MD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Treatment
Daily active stimulation for 8 weeks
Device: Active treatment
Daily active ultrasound stimulation
Sham Comparator: Control
Daily sham stimulation, for 8 weeks, which will look and feel the same as active stimulation, but with no ultrasound energy entering the body
Device: Sham (No Treatment)
Daily sham ultrasound stimulation

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Adverse Events
Time Frame: 12 weeks
All adverse events (AEs) regardless of treatment group that occur over the 12 week enrollment period will be coded and summarized by frequency, severity, and relatedness using the latest MedDRA version (v28.1).
12 weeks
Adherence to Therapy
Time Frame: 8 weeks
Proportion of patients adherent to treatment, defined by completing ≥70% of the 56 scheduled ultrasound treatments
8 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
American College of Rheumatology (ACR) 20, 50 and 70 response rates
Time Frame: Week 8
Difference between treatment and control groups in the proportion of subjects who achieve at least 20%, 50%, and 70% improvement from baseline to Week 8 in tender and swollen joint counts of 28 joints (scale 0=best to 28=worst) and 3 out of the following 5 measures: Health Assessment Questionnaire Disability Index (HAQ-DI) score (scale 0=no difficulty to 3=unable to do), subject global assessment (0=best to 10=worst), subject pain (0=no pain to 10=worst), evaluator's global assessment (0=best to 10=worst), or high sensitivity C-reactive protein (hsCRP) concentration (mg/mL).
Week 8
Change in Disease Activity Score-28 for Rheumatoid Arthritis with CRP (DAS28-CRP).
Time Frame: Week 8
Defined by EULAR based on a composite score of 4 items: tender and swollen joint counts of 28 joints (scale 0=best to 28=worst), subject global assessment (0=best to 10=worst) and high-sensitivity C-reactive protein (hsCRP) concentration (mg/L). DAS28-CRP response based on the minimal clinically important difference (MCID) of -1.2 from baseline to week 8.
Week 8
Change in Heath Assessment Questionnaire Disability Index (HAQ-DI)
Time Frame: Week 8
Haq-DI assesses physical function through eight daily activity domains (scale 0=no difficulty to 3=unable to do). Change from baseline to week 8 based on the MCID of -0.22.
Week 8
Change in Clinical Disease Activity Index (CDAI) score for Rheumatoid Arthritis
Time Frame: Week 8
The CDAI assesses disease activity by summing tender joint count (TJC), swollen joint count (SJC), patient global assessment (PGA), and physician global assessment (EGA). CDAI will be assessed from Baseline to Week 8.
Week 8
Change in Simplified Disease Activity Index (SDAI) for Rheumatoid Arthritis (RA)
Time Frame: Week 8
The SDAI is a measure of disease activity that includes all the 4 components of the CDAI, plus CRP. SDAI will be assessed from baseline to Week 8.
Week 8
Change in high sensitivity CRP (hsCRP)
Time Frame: Weeks 2, 4, 6, and 8
The primary endpoint is the change in hsCRP from baseline to weeks 2, 4, 6 and 8.
Weeks 2, 4, 6, and 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Surf Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 20, 2026

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

April 1, 2027

Study Registration Dates

First Submitted

December 2, 2025

First Submitted That Met QC Criteria

December 17, 2025

First Posted (Actual)

December 19, 2025

Study Record Updates

Last Update Posted (Actual)

July 7, 2026

Last Update Submitted That Met QC Criteria

July 2, 2026

Last Verified

July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • SURF-CLN-003

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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