Clinical trial NCT05417854: Ultrasound Treatment for Rheumatoid Arthritis Study [ULTRA Study]
Official title: Ultrasound Treatment for Rheumatoid Arthritis Study [ULTRA Study]
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Rheumatoid Arthritis
Lead sponsor: SecondWave Systems Inc.
Sponsor class: INDUSTRY
Collaborators: name: University of Minnesota
name: DARPA (United States Department of Defense)
First posted: 2022-06-14
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DEVICE_FEASIBILITY

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Within-arm change in the Disease Activity Score (DAS-28-CRP) from baseline to the completion of an up-to 8-week treatment period.
timeFrame: 8 weeks
Secondary outcomes:
Other outcomes:
measure: Within-arm change of serum c-reactive protein (CRP) concentration.
timeFrame: 8 weeks
measure: Within-arm change of serum erythrocyte sedimentation rate (ESR).
timeFrame: 8 weeks
measure: Within-arm change of serum cortisol levels.
timeFrame: 8 weeks
measure: Within-arm change of serum Tumor Necrosis Factor (TNFa) concentration.
timeFrame: 8 weeks
measure: Within-arm change of serum Interleukin-1 beta (IL-1beta) concentration.
timeFrame: 8 weeks
measure: Within-arm change of serum Interleukin-6 (IL-6) concentration.
timeFrame: 8 weeks
measure: Within-arm change of serum Interleukin-6 (IL-8) concentration.
timeFrame: 8 weeks
measure: Within-arm change of serum Interferon gamma (IFN-gamma) concentration.
timeFrame: 8 weeks
measure: Within-arm change on the Multidimensional Health Assessment Questionnaire (HAQ).
timeFrame: 8 weeks
measure: Within-arm change on the EQ-5D health questionnaire.
timeFrame: 8 weeks
measure: Exit interview questions.
timeFrame: End of study participation
Locations:
city: Minneapolis
country: United States
facility: University of Minnesota - Phillips-Wangensteen Building
state: Minnesota
city: Minneapolis
country: United States
facility: University of Minnesota Health Clinics and Surgery Center
state: Minnesota
Study officials:
affiliation: University of Minnesota Medical School, Division of Rheumatic and Autoimmune Diseases
name: Erik Peterson, M.D.
role: PRINCIPAL_INVESTIGATOR
References: