Ultrasound Treatment for Rheumatoid Arthritis Study [ULTRA Study] (ULTRA)

The research objective is to assess efficacy of spleen ultrasound stimulation in the treatment of rheumatoid arthritis (RA) in a pilot study.

Specific Aims:

• Measure RA disease activity and clinical metrics during and after an 8-week course of spleen-directed daily ultrasound treatments.
• Measure molecular correlates, including Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), cortisol and cytokine levels, of rheumatoid arthritis disease activity during spleen-directed daily ultrasound treatments.

Study Overview

• Status: Completed
• Conditions: Rheumatoid Arthritis
• Intervention / Treatment: Device: Splenic Ultrasound

Detailed Description

Ultrasound is widely used in human medicine because it is safe, non-invasive, and painless. The same kind of ultrasound that is used for imaging (for example, to visualize babies in utero) may be able to treat inflammatory diseases including Rheumatoid Arthritis.

Multiple studies in animals with hyper-inflammation conditions (e.g., inflammatory arthritis and sepsis/lipopolysaccharide [LPS] injections) and recent human studies (e.g., for the treatment of joint inflammation in Rheumatoid Arthritis) have shown that ultrasound applied to the spleen can suppress blood/genetic markers of inflammation.

This study will employ investigational ultrasound devices produced by SecondWave Systems called the MINI ultrasound system.

This is a pilot single-arm treatment trial in which up to 15 study participants will receive noninvasive splenic-ultrasound therapy over eight weeks (five daily stimulation sessions per week). Clinical outcomes will be compared from baseline to end of the 8-week treatment period. Investigational splenic-ultrasound therapy will be delivered with the SecondWave MINI ultrasound system. The objective of the study is to assess the safety and potential efficacy for the MINI system for treatment of Rheumatoid Arthritis.

For ultrasound stimulation, a small wearable ultrasound device is positioned on the upper left abdomen area over the ribs. Study personnel will use an ultrasound imaging device to locate the spleen and to position the wearable MINI device in a proper location around the ribs area. Daily stimulation consists of an approximately 18-minute period for application of ultrasound to the spleen. Collection of clinical outcome data, patient-reported assessments, and blood draws collected at the 5 study visits to assess biomarkers of inflammation will be performed in each participant throughout the study.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota Health Clinics and Surgery Center
    • Minneapolis, Minnesota, United States, 55455
      • University of Minnesota - Phillips-Wangensteen Building

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Males and females ages 18 and above

2. Must carry a diagnosis of rheumatoid arthritis, as defined by the American College of Rheumatology in 2010: (https://www.rheumatology.org/Portals/0/Files/2010_revised_criteria_classification_ra.pdf)

   - Classification as "definite RA" is based on the confirmed presence of synovial thickening in at least 1 joint, absence of an alternative diagnosis that better explains the synovitis, and achievement of a total score of 6 or greater (of a possible 10) from the individual scores in 4 domains: number and site of involved joints (score range 0-5), serologic abnormality (score range 0-3), elevated acute-phase response (score range 0-1), and symptom duration (2 levels; range 0-1)

3. Exhibiting symptoms or signs of inadequate inflammatory disease control according to one of two measures:

   1. Multidimensional HAQ score of greater than 0.3
   2. DAS-28-CRP greater than 3.2 (http://www.phusewiki.org/wiki/index.php?title=Disease_Activity_Score_-_CRP_(DAS-CRP)
4. Candidate participant's rheumatoid arthritis medical therapy should be stable for two weeks leading up to the study. Moreover, participants must be willing to maintain their current medication regimen throughout the study enrollment period (in adjunct to the additional investigational ultrasound treatment)

Exclusion Criteria:

1. Active bacterial or viral infection
2. Pregnant women or those trying to become pregnant
3. Receiving active chemotherapy or immunotherapy to treat malignancy within 30 days prior to enrollment
4. Having received Rituximab monoclonal antibody medication within 30 days prior to enrollment
5. Presence of an implanted device
6. Asplenia
7. Splenomegaly
8. Ascites
9. Recent abdominal surgery
10. Currently participating in an investigational drug or device study
11. Open wound/sores near stimulation sites
12. Inability to perform minimal daily self-cares associated with feeding/dressing, according to HAQ
13. Any other clinical reasons deemed by the investigators of the study in which the patient would not be an appropriate candidate for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ultrasound Group	Device: Splenic Ultrasound; Daily ultrasound application to the spleen of approximately 18 minutes per day, 5 days per week for up to 8 weeks, in addition to standard clinical care.; Other Names: SecondWave Systems investigational MINI device

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Within-arm change in the Disease Activity Score (DAS-28-CRP) from baseline to the completion of an up-to 8-week treatment period.	A decrease in Disease Activity Score indicates an improved outcome.	8 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Within-arm change of serum c-reactive protein (CRP) concentration.		8 weeks
Within-arm change of serum erythrocyte sedimentation rate (ESR).		8 weeks
Within-arm change of serum cortisol levels.		8 weeks
Within-arm change of serum Tumor Necrosis Factor (TNFa) concentration.		8 weeks
Within-arm change of serum Interleukin-1 beta (IL-1beta) concentration.		8 weeks
Within-arm change of serum Interleukin-6 (IL-6) concentration.		8 weeks
Within-arm change of serum Interleukin-6 (IL-8) concentration.		8 weeks
Within-arm change of serum Interferon gamma (IFN-gamma) concentration.		8 weeks
Within-arm change on the Multidimensional Health Assessment Questionnaire (HAQ).	A decreased score on the HAQ indicates an improved outcome.	8 weeks
Within-arm change on the EQ-5D health questionnaire.	A decreased score on questions from the EQ-5D indicates an improved outcome.	8 weeks
Exit interview questions.	These questions ask the participant about whether they feel that they have benefited from the investigational treatment, whether they would recommend the investigational treatment to others, and the comfort level of the investigational treatment.	End of study participation

Collaborators and Investigators

• Sponsor: SecondWave Systems Inc.
• Collaborators: University of Minnesota; DARPA (United States Department of Defense)
• Investigators: Principal Investigator: Erik Peterson, M.D., University of Minnesota Medical School, Division of Rheumatic and Autoimmune Diseases

Study record dates

Study Major Dates

• Study Start (Actual): June 29, 2022
• Primary Completion (Actual): July 19, 2023
• Study Completion (Actual): September 25, 2023

Study Registration Dates

• First Submitted: June 7, 2022
• First Submitted That Met QC Criteria: June 10, 2022
• First Posted (Actual): June 14, 2022

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 10, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Connective Tissue Diseases; Arthritis; Arthritis, Rheumatoid
• Other Study ID Numbers: Pro00062049; 140D0419C0092 (Other Grant/Funding Number: Department of Defense)

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