UNITE Study (UMN-GE) for COVID-19

Study Overview
=================
Brief Summary
-----------------
The research objective of the UNITE Study is to assess the potential efficacy of ultrasound application to the spleen in the treatment of coronavirus disease 2019 (COVID-19) in a pilot study. Specific Aims: Determine the efficacy of splenic ultrasound in affecting markers of systemic inflammation in COVID-19 infection. Evaluate the potential efficacy of splenic ultrasound in affecting clinical outcomes in COVID-19 infection.

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 COVID-19. COVID-19 is a disease caused by infection with the SARS-CoV-2 virus. Some COVID-19 patients develop a severe respiratory disease called acute respiratory distress syndrome and this disease is caused, in part, by a significant increase in inflammatory factors. Clinical therapies that reduce this elevated inflammation in the body (e.g., inflammation molecules in your body called cytokines) may be capable of diminishing symptoms in severe cases of COVID-19. Multiple studies in animals with hyper-inflammation conditions (e.g., inflammatory arthritis and sepsis/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. Similar inflammatory markers, or cytokines, are elevated in the lungs of COVID-19 patients and believed to cause severe symptoms. Splenic ultrasound can potentially lower these inflammatory cytokines without hindering antibody production, leading to clinical improvements in COVID-19 patients. This study will employ ultrasound devices produced by General Electric (GE LOGIQ E10 device with C1-6 ultrasound probe) that are currently used in hospitals and approved for diagnostic imaging by the FDA. The ultrasound energies applied to the spleen in this study in COVID-19 patients will not exceed what is currently approved for diagnostic imaging with those GE ultrasound devices. There will be two groups in this study with 15 participants in each group. One group will receive ultrasound application to the spleen, in addition to the standard clinical care. A control group will receive standard clinical care without splenic ultrasound. Each ultrasound application session will last about 15-20 minutes per day for 7 days, unless the participant is discharged sooner. For ultrasound stimulation, a small gel-coated probe is positioned on the upper left abdomen area over the ribs. The ultrasound session includes a period of 5-10 minutes when study personnel use the ultrasound device to locate the spleen and to position the ultrasound probe in a proper location around the ribs area, and an approximately 10-minute period for application of ultrasound to the spleen. Collection of clinical outcome data and daily blood draws will be performed in each participant throughout the study. Additional data collected from each participant during their routine clinical care beyond their study involvement will also be analyzed together with the study data to evaluate the specific aims of the clinical trial.

Official Title
-----------------
Ultrasound Neural and Immunomodulation Treatment Evaluation Study (UMN-GE) for COVID-19

Conditions
-----------------
Covid19, Cytokine Storm, Inflammation

Intervention / Treatment
-----------------
* Device: Splenic ultrasound


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 and above Positive for SARS-CoV-2 (via PCR) Decreased blood oxygen saturation: Room air SaO2 < 94% and/or requiring supplemental oxygen to maintain SaO2 > 90% Admission to the hospital Exclusion Criteria: Pregnant women Asplenia Ascites Open wound/sores near the stimulation site Recent abdominal surgery Splenomegaly Mechanically ventilated (if patient goes onto mechanical ventilation while participating in the study, they can continue ultrasound treatment if recommended by standard of care clinician and investigators of the study) Comfort care status Any other clinical reasons deemed by the investigators of the study in which the patient would not be an appropriate candidate for the study

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The participants will be randomized to two groups: ultrasound group and control group. All participants will still receive standard clinical care. The ultrasound group will receive daily ultrasound application to the spleen for up to 7 days, in addition to the standard clinical care. The control group will receive standard clinical care without ultrasound stimulation.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ultrasound Group<br>Daily ultrasound application to the spleen of approximately 10 minutes for up to 7 days, in addition to standard clinical care. | Device: Splenic ultrasound<br>* GE LOGIQ E10 device with C1-6 ultrasound probe<br>|
| No Intervention: Control Group<br>Standard clinical care with no ultrasound stimulation. | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Between-arm change of IL-6 levels from baseline to end of treatment between groups |  | Baseline to Day 8 (end of treatment; or date of discharge) | 
| Between-arm change of IL-1β levels from baseline to end of treatment between groups |  | Baseline to Day 8 (end of treatment; or date of discharge) | 
| Between-arm change of CRP levels from baseline to end of treatment between groups |  | Baseline to Day 8 (end of treatment; or date of discharge) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in time to recovery | Day of recovery is defined as the first day on which the subject satisfies this category from the ordinal scale: Hospitalized, no oxygen therapy | Baseline to date of recovery, assessed up to 21 days | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
ultrasound, ultrasound stimulation, immunomodulation, neuromodulation, spleen