UNITE Study (UMN-GE) for COVID-19

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

The research objective of the UNITE Study is to assess device feasibility of ultrasound application to the spleen to assess its effect on coronavirus disease 2019 (COVID-19) in a pilot study with an off-the-shelf ultrasound GE device originally used for diagnostic applications.

Specific Aims:

1. Determine the feasibility of splenic ultrasound with an ultrasound 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 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 possible clinical improvements in COVID-19 patients.

This study will employ off-the-shelf 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 various 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.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • 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 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

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
IL-6 changes	Percentage of participants with observed change in IL-6 level	Baseline to Day 8 (end of stimulation; or date of discharge)
IL-1β changes	Percentage of participants with observed change in IL-1β level	Baseline to Day 8 (end of stimulation; or date of discharge)
CRP changes	Percentage of participants with observed change in CRP level	Baseline to Day 8 (end of stimulation; 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

Other Outcome Measures

Outcome Measure	Time Frame
Change in death rate	Baseline to date of discharge or date of death, whichever came first, assessed up to 6 months
Change in rate of requiring mechanical ventilation	Baseline to date of discharge or date of death, whichever came first, assessed up to 6 months
Change in duration of hypoxemia	Baseline to date of discharge or date of death, whichever came first, assessed up to 6 months
Change in D-dimer levels	Baseline to Day 8 (end of stimulation; or date of discharge)
Change in serum cytokine concentration of TNF	Baseline to Day 8 (end of stimulation; or date of discharge)
Change in serum cytokine concentration of IL-10	Baseline to Day 8 (end of stimulation; or date of discharge)
Change in serum cytokine concentration of IFN-gamma	Baseline to Day 8 (end of stimulation; or date of discharge)
Change in serum cytokine concentration of IL-18	Baseline to Day 8 (end of stimulation; or date of discharge)
Change in serum cytokine concentration of IL2R-alpha	Baseline to Day 8 (end of stimulation; or date of discharge)
Change in serum cytokine concentration of IL-4	Baseline to Day 8 (end of stimulation; or date of discharge)
Change in RNAseq identified pro-inflammatory pathways	Baseline to Day 8 (end of stimulation; or date of discharge)

Collaborators and Investigators

• Sponsor: University of Minnesota
• Collaborators: General Electric Research; DARPA (Department of Defense)
• Investigators: Principal Investigator: Hubert Lim, PhD, 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): January 14, 2021
• Primary Completion (Actual): March 15, 2021
• Study Completion (Actual): April 7, 2021

Study Registration Dates

• First Submitted: January 5, 2021
• First Submitted That Met QC Criteria: January 6, 2021
• First Posted (Actual): January 8, 2021

Study Record Updates

• Last Update Posted (Estimated): 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: ultrasound; neuromodulation; immunomodulation; spleen; ultrasound stimulation
• 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: OTOL-2020-29216

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