UNITE Study (UMN-SW) for COVID-19

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

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.

Study Overview

• Status: Completed
• Conditions: Inflammation; Covid19; Cytokine Storm
• 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 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.

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Burnsville, Minnesota, United States, 55337
      • M Health Fairview Ridges Hospital
    • Saint Paul, Minnesota, United States, 55102
      • M Health Fairview St. Joseph's Hospital

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Group
Experimental: Ultrasound Group; Daily ultrasound application to the spleen of approximately 18 minutes for up to 7 days, in addition to standard clinical care.	Device: Splenic Ultrasound; Daily ultrasound application to the spleen of approximately 18 minutes for up to 7 days, 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
IL-6 levels	Percentage of participants with observed change in IL-6 levels	Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
IL-1β levels	Percentage of participants with observed change in IL-1β levels	Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalized days based on the ordinal scale	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	Baseline to date of recovery, assessed up to 14 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hypoxemia duration	Change in duration of hypoxemia	Baseline to date of discharge or date of death, whichever came first, assessed up to 6 months
Mechanical ventilation	Change in rate of requiring mechanical ventilation	Baseline to date of discharge or date of death, whichever came first, assessed up to 6 months
Mortality rate	Change in mortality rate	Baseline to date of discharge or date of death, whichever came first, assessed up to 6 months
Ordinal scale values over time	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 stimulation; last observation carried forward if date of discharge or death is earlier)
CRP levels	Change in CRP levels	Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
D-dimer levels	Change in D-dimer levels	Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
TNF levels	Change in serum cytokine concentration of TNF	Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
IL-10 levels	Change in serum cytokine concentration of IL-10	Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
IFN-gamma levels	Change in serum cytokine concentration of IFN-gamma	Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
IL-18 levels	Change in serum cytokine concentration of IL-18	Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
IL2R-alpha levels	Change in serum cytokine concentration of IL2R-alpha	Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
IL-4 levels	Change in serum cytokine concentration of IL-4	Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)
RNAseq pathways	Change in RNAseq identified pro-inflammatory pathways	Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier)

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: SecondWave Systems Inc.; DARPA (United States Department of Defense); MCDC (United States Department of Defense)
• Investigators: Principal Investigator: Erik Peterson, M.D., University of Minnesota; Principal Investigator: Andrew Olson, M.D., University of Minnesota

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): April 29, 2021
• Primary Completion (Actual): February 1, 2022
• Study Completion (Actual): February 11, 2022

Study Registration Dates

• First Submitted: April 20, 2021
• First Submitted That Met QC Criteria: April 20, 2021
• First Posted (Actual): April 22, 2021

Study Record Updates

• Last Update Posted (Actual): May 3, 2024
• Last Update Submitted That Met QC Criteria: May 1, 2024
• Last Verified: May 1, 2024

More Information

Terms related to this study

• Keywords: Inflammation; Covid19; Cytokine Storm
• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Systemic Inflammatory Response Syndrome; Shock; COVID-19; Inflammation; Cytokine Release Syndrome
• Other Study ID Numbers: Pro00050829

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No