UNITE Study (UMN-SW) for COVID-19

Ultrasound Neural and Immunomodulation Treatment Evaluation Study (UMN-SW) for COVID-19 With Wearable Ultrasound Device

SecondWave Systems Inc., DARPA (United States Department of Defense), MCDC (United States Department of Defense)

The research objective of the UNITE Study is to assess the potential efficacy of ultrasound application to the spleen using a small wearable ultrasound system in the treatment of coronavirus disease 2019 (COVID-19) in a pilot study. Specific Aims: Determine the efficacy of splenic ultrasound with a new wearable device in affecting markers of systemic inflammation in COVID-19 infection between an ultrasound group versus a control group; and Evaluate the potential efficacy of splenic ultrasound with this new wearable device in affecting clinical outcomes in COVID-19 infection in the ultrasound group compared to a control group.

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 investigational ultrasound devices produced by SecondWave Systems called the MINI (Miniature Immunotherapy and Neuromodulation Instrument). There will be two groups in this study with 29 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 30 minutes per day for 7 days, unless the participant is discharged sooner. For ultrasound stimulation, a small wearable ultrasound device is positioned on the upper left abdomen area over the ribs. The ultrasound session on the first study day includes a period of 5-10 minutes when study personnel 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 and daily blood draws will be performed in each participant throughout the study through Day 8. 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.

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.

Daily ultrasound application to the spleen of approximately 18 minutes for up to 7 days, in addition to standard clinical care.

Daily ultrasound application to the spleen of approximately 18 minutes for up to 7 days, in addition to standard clinical care

Mean change in the number of days of hospitalized state of patients (based on the ordinal scale) in the ultrasound group versus the control group

Between-arm comparison of area under the curve of ordinal scale values (absolute and normalized) from baseline to end of treatment between groups.

Baseline to Day 8 (end of treatment; last observation carried forward if date of discharge or death is earlier)

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 at a flow rate of 2 L/min or greater 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 SOC clinician and investigators of this 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

First-in-human demonstration of splenic ultrasound stimulation for non-invasively controlling inflammation