UNITE Study (UCSD-SW) for COVID-19 (UNITE)

• ClinicalTrials.gov Identifier: NCT04803409
• Recruitment Status: Active, not recruiting
• First Posted: March 17, 2021
• Last Update Posted: December 10, 2021
• Sponsor: Imanuel Lerman
• Collaborators: SecondWave Systems Inc.; MCDC (Unites States Department of Defense)
• Information provided by (Responsible Party): Imanuel Lerman, University of California, San Diego

Study Description

Brief Summary:

The research objective of the UNITE Study is to assess the potential efficacy of ultrasound application to the spleen using a small wearable ultrasound system in the treatment of coronavirus disease 2019 (COVID-19) in a pilot study.

Specific Aims:

Determine the efficacy of splenic ultrasound in affecting markers of systemic inflammation in COVID-19 infection.

Evaluate the potential efficacy of splenic ultrasound in affecting clinical outcomes in COVID-19 infection.

Condition or disease:

Covid19:

Cytokine Storm Inflammation

Device:

Splenic Ultrasound

Phase:

Not Applicable

Condition or disease	Intervention/treatment	Phase
Covid19	Device: Splenic Ultrasound	Not Applicable

Detailed Description:

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 System (Miniature Immunotherapy and Neuromodulation Instrument System).

There will be two groups in this study with 20 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, and 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 Design Go to sections Study Type : Interventional (Clinical Trial) Estimated Enrollment : 40 participants Allocation: Randomized Intervention Model: Parallel Assignment 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: Other

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 40 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: 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.
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Ultrasound Neural and Immunomodulation Treatment Evaluation Study (UCSD-SW) for COVID-19
• Actual Study Start Date: March 22, 2021
• Estimated Primary Completion Date: December 15, 2021
• Estimated Study Completion Date: December 31, 2021

Arms and Interventions

Arm	Intervention/treatment
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; Splenic Ultrasound: Daily ultrasound application to the spleen of approximately 18 minutes for up to 7 days, in addition to standard clinical care
No Intervention: Control Group; Control Group

Outcome Measures

Primary Outcome Measures :

1. IL-6 Change [ Time Frame: Baseline to Day 8 (end of treatment; or date of discharge) ]
   Between-arm change of IL-6 levels from baseline to end of treatment between groups
2. IL-1β [ Time Frame: Baseline to Day 8 (end of treatment; or date of discharge ]
   Between-arm change of IL-1β levels from baseline to end of treatment between groups
3. CRP [ Time Frame: Baseline to Day 8 (end of treatment; or date of discharge) ]
   Between-arm change of CRP levels from baseline to end of treatment between groups

Secondary Outcome Measures :

1. Change in time to recovery [ Time Frame: Baseline to date of recovery, assessed up to 6 months ]
   Day of recovery is defined as the first day on which the subject satisfies this category from the ordinal scale: Hospitalized, no oxygen therapy

Other Outcome Measures:

1. Change in death rate [ Time Frame: : Baseline to date of discharge or date of death, whichever came first, assessed up to 6 months ]
   Change in death rate
2. Change in rate of requiring mechanical ventilation [ Time Frame: Baseline to date of discharge or date of death, whichever came first, assessed up to 6 months ]
   Change in rate of requiring mechanical ventilation
3. Change in duration of hypoxemia [ Time Frame: Baseline to date of discharge or date of death, whichever came first, assessed up to 6 months ]
   Change in duration of hypoxemia
4. Change in serum cytokine concentration of TNF [ Time Frame: Baseline to Day 8 (end of treatment; or date of discharge) ]
   Change in serum cytokine concentration of TNF
5. Change in serum cytokine concentration of IL-10 [ Time Frame: Baseline to Day 8 (end of treatment; or date of discharge) ]
   Change in serum cytokine concentration of IL-10
6. Change in serum cytokine concentration of IFN-gamma [ Time Frame: Baseline to Day 8 (end of treatment; or date of discharge) ]
   Change in serum cytokine concentration of IFN-gamma
7. Change in serum cytokine concentration of IL-18 [ Time Frame: Baseline to Day 8 (end of treatment; or date of discharge) ]
   Change in serum cytokine concentration of IL-18
8. Change in serum cytokine concentration of IL2R-alpha [ Time Frame: Baseline to Day 8 (end of treatment; or date of discharge) ]
   Change in serum cytokine concentration of IL2R-alpha
9. Change in serum cytokine concentration of IL-4 [ Time Frame: Baseline to Day 8 (end of treatment; or date of discharge) ]
   Change in serum cytokine concentration of IL-4
10. Change in D-dimer levels [ Time Frame: Baseline to Day 8 (end of treatment; or date of discharge ]
    Change in D-dimer levels

Eligibility Criteria

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

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
• 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
• On-duty Federal Employees and Military Personnel
• Patient without decision making capacity as determined by clinical judgement informed by communication with the UCSD primary Hospitalist team
• Any other clinical reasons deemed by the investigators of the study in which the patient would not be an appropriate candidate for the study

Contacts and Locations

Locations

United States, California

University of California San Diego

San Diego, California, United States, 92037

Sponsors and Collaborators

Imanuel Lerman

SecondWave Systems Inc.

MCDC (Unites States Department of Defense)

More Information

• Responsible Party: Imanuel Lerman, Asst Clin Prof, University of California, San Diego
• ClinicalTrials.gov Identifier: NCT04803409
• Other Study ID Numbers: 201611
• First Posted: March 17, 2021
• Last Update Posted: December 10, 2021
• Last Verified: December 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Additional relevant MeSH terms:

COVID-19; Respiratory Tract Infections; Infections; Pneumonia, Viral; Pneumonia; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases