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| Name | Class |
|---|---|
| General Electric Research | INDUSTRY |
| DARPA (Department of Defense) | UNKNOWN |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ultrasound Group | Experimental | Daily ultrasound application to the spleen of approximately 10 minutes for up to 7 days, in addition to standard clinical care. |
|
| Control Group | No Intervention | Standard clinical care with no ultrasound stimulation. |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Splenic ultrasound | Device | GE LOGIQ E10 device with C1-6 ultrasound probe |
|
| 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) |
| 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 |
| Measure | Description | 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Hubert Lim, PhD | University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| M Health Fairview St. Joseph's Hospital | Saint Paul | Minnesota | 55102 | United States |
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| Label | URL |
|---|---|
| First-in-human demonstration of splenic ultrasound stimulation for non-invasively controlling inflammation | View source |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| ICF | No | No | Yes | Informed Consent Form | Dec 23, 2020 | Apr 20, 2021 | ICF_000.pdf |
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| ID | Term |
|---|---|
| D000086382 | COVID-19 |
| D000080424 | Cytokine Release Syndrome |
| D007249 | Inflammation |
| ID | Term |
|---|---|
| D011024 | Pneumonia, Viral |
| D011014 | Pneumonia |
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
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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.
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| 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) |
| D014777 |
| Virus Diseases |
| D018352 | Coronavirus Infections |
| D003333 | Coronaviridae Infections |
| D030341 | Nidovirales Infections |
| D012327 | RNA Virus Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| D018746 | Systemic Inflammatory Response Syndrome |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D012769 | Shock |