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| Name | Class |
|---|---|
| SecondWave Systems Inc. | INDUSTRY |
| United States Department of Defense | FED |
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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:
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Ultrasound Group | Experimental | Daily ultrasound application to the spleen of approximately 18 minutes for up to 7 days, in addition to standard clinical care. |
|
| Control Group | No Intervention | Control Group |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Splenic Ultrasound | Device | Daily ultrasound application to the spleen of approximately 18 minutes for up to 7 days, in addition to standard clinical care |
|
| 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) |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Erik Peterson, M.D. | University of Minnesota | Principal Investigator |
| Andrew Olson, M.D. | University of Minnesota | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| M Health Fairview Ridges Hospital | Burnsville | Minnesota | 55337 | United States | ||
| M Health Fairview St. Joseph's Hospital |
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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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| 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 CRP levels |
| Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier) |
| Hypoxemia duration | Change in duration of hypoxemia | Baseline to date of discharge or date of death, whichever came first, assessed up to 6 months |
| D-dimer levels | Change in D-dimer levels | Baseline to Day 8 (end of stimulation; or date of discharge or death if earlier) |
| 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 |
| 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) |
| Saint Paul |
| Minnesota |
| 55102 |
| United States |
| 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 |