Clinical trial NCT04854798: UNITE Study (UMN-SW) for COVID-19
Official title: Ultrasound Neural and Immunomodulation Treatment Evaluation Study (UMN-SW) for COVID-19 With Wearable Ultrasound Device
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Covid19
Cytokine Storm
Inflammation
Keywords: Covid19
Cytokine Storm
Inflammation
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: SecondWave Systems Inc.
name: DARPA (United States Department of Defense)
name: MCDC (United States Department of Defense)
First posted: 2021-04-22
Enrollment: 58
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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.
Primary purpose: DEVICE_FEASIBILITY

Brief summary: The research objective of the UNITE Study is to assess device feasibility of ultrasound application to the spleen using a small wearable ultrasound system to assess its effect on coronavirus disease 2019 (COVID-19) in a pilot study using an early stage prototype device.

Specific Aims:

1. Determine the feasibility of splenic ultrasound with a prototype wearable device in affecting physiological markers in COVID-19 infected patients between an ultrasound group versus a control group for the primary analyses; and
2. Evaluate the potential capabilities of splenic ultrasound with this prototype wearable device in affecting additional outcomes in COVID-19 infected patients in the ultrasound group compared to a control group.

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 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.

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 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

Primary outcomes:
measure: IL-6 levels
timeFrame: Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
measure: IL-1β levels
timeFrame: Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
Secondary outcomes:
measure: Hospitalized days based on the ordinal scale
timeFrame: Baseline to date of recovery, assessed up to 14 days
Other outcomes:
measure: Ordinal scale values over time
timeFrame: Baseline to Day 8 (end of stimulation; last observation carried forward if date of discharge or death is earlier)
measure: CRP levels
timeFrame: Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
measure: Hypoxemia duration
timeFrame: Baseline to date of discharge or date of death, whichever came first, assessed up to 6 months
measure: D-dimer levels
timeFrame: Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
measure: Mechanical ventilation
timeFrame: Baseline to date of discharge or date of death, whichever came first, assessed up to 6 months
measure: Mortality rate
timeFrame: Baseline to date of discharge or date of death, whichever came first, assessed up to 6 months
measure: TNF levels
timeFrame: Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
measure: IL-10 levels
timeFrame: Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
measure: IFN-gamma levels
timeFrame: Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
measure: IL-18 levels
timeFrame: Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
measure: IL2R-alpha levels
timeFrame: Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
measure: IL-4 levels
timeFrame: Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
measure: RNAseq pathways
timeFrame: Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
Locations:
city: Burnsville
country: United States
facility: M Health Fairview Ridges Hospital
state: Minnesota
city: Saint Paul
country: United States
facility: M Health Fairview St. Joseph's Hospital
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: Erik Peterson, M.D.
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Minnesota
name: Andrew Olson, M.D.
role: PRINCIPAL_INVESTIGATOR
References: