Ultrasound of the Spleen Utilizing Low-energy (Diagnostic Level) Insonification.

Effects of Ultrasound Insonification of the Spleen on Platelet Activity and Coagulation Biomarkers in Healthy Human Subjects

This is a three-cohort, randomized, double-blinded , sham-controlled, single-center, early feasibility research trial to determine whether organ-specific biologic effects on platelet activity and coagulation are achievable through selective ultrasound of the spleen utilizing low-energy (diagnostic-level) insonification.

• Group 1: Focused insonification at center of the spleen.
• Group 2: Prolonged duration insonification at center of the spleen
• Group 3: Prolonged duration insonification across the spleen.

Participants will receive 30 minutes of sham stimulation in the randomized group that is assigned to them, followed by active stimulation within the same group. Blood biomarkers (local and systemic) will be measured before and at several timepoints after stimulation to measure the molecular and cellular effects of the device

Inclusion Criteria

1. Provision of signed and dated informed consent form
2. Willingness to comply with all study procedures and availability for the entire study duration
3. Male or female, aged 18 to 50 years
4. Individuals without physical disabilities or conditions/diseases that may make them incapable of undergoing the study procedure or otherwise places them at a greater risk of harm.
5. Individuals without significant past medical or surgical histories that would render them at a greater risk of harm
6. Individuals that are considered English Proficient due to the study requirements to follow verbal commands during the ultrasound session
7. Individuals that are considered active as assessed by type of activity (i.e., walking, running, etc.) and number of hours a week performing the various activities
8. Willing to adhere to the ultrasound study regimen
9. Individuals able to attend all study visits at approximately the same time of day (i.e., 8-12 pm)
10. Individuals able to comprehend the study goals and procedures, and can provide informed consent for participation

Exclusion Criteria:

1. Individuals participating in another research study that may affect the conduct or results of this study

2. Individuals considered substantially overweight or obese via body mass index (BMI > 30)

3. Individuals having or exhibiting any of the following:

   • surgery in the past 90 days
   • previous surgery of the spleen or splenectomy, esophagus, lungs, stomach, duodenum, or liver
   • recent traumatic injury, including intracerebral hemorrhage and visceral injury
   • end stage renal disease and/or uremia
   • active malignancy
   • previous leukemia and/or lymphoma
   • human immunodeficiency virus infection or AIDS
   • rheumatoid arthritis or other immune-mediated diseases (e.g. inflammatory bowel disease)
   • arrhythmias, including but not limited to, atrial fibrillation, atrial flutter, clinically significant bradycardia, ventricular arrhythmias, and A-V block
   • implanted pacemaker or cardioverter/defibrillator (AICD)
   • history of stable or unstable angina, myocardial infarction, angioplasty, or coronary arterial by-pass grafting surgery
   • history of stroke or TIA
   • history of deep venous thrombosis (DVT) and/or pulmonary embolism (PE)
   • previous episodes of pancreatitis
   • spinal disorders
   • chronic pain syndromes
   • stage III-IV pressure ulcers
   • sickle cell anemia or other anemia syndromes
   • diagnosed with fever of unknown origin (FUO)
   • previously or currently implanted vagus nerve stimulator
   • previously or currently implanted spinal cord stimulator or other chronically implanted electronic medical device
   • history of seizures
   • history of cancer

4. Individuals who have taken any of the following medications within two weeks of receiving ultrasound delivery:

   • anti-coagulants (warfarin, Xarelto)
   • anti-platelet agent (aspirin, clopidogrel)
   • anti-inflammatory (aspirin, NSAIDs)
   • anti-hypertensive (α-methyldopa)
   • epinephrine-related drugs, norepinephrine-related drugs, and drugs that stimulate release of epinephrine and/or norepinephrine (Micronefrin, Asthmanefrin)
   • immunosuppressive agents (steroids, newer immunomodulatory drugs)
   • alpha and/or beta-adrenoceptor blocking agents
   • anti-seizure medications
   • other medications, supplements, etc. that may interfere with the ultrasound delivery or study results

5. Individuals with a substance abuse (alcoholism or other) problem

6. Individuals that consumed alcohol within 7 days of the baseline visit

7. Individuals currently using or have used cocaine, heroin, marijuana, or other illicit recreational drugs within the past 3 months

8. Prisoners

9. Participant has a history of thrombocytopenia (platelet count <100k)

10. Participant has reported coagulopathy (elevated PT, PTT, elevated activated clotting time (ACT))

11. Participant has internal bleeding, external bleeding, easy bruising

12. Participant has a history of abnormal bleeding or blood disorder, including anemia or anemia-related disorders

13. Participant has a history of thrombocytopenia (platelet count <100k)

14. Participant has a history of coagulopathy, including hemophilia, stroke, pulmonary embolism, myocardial infarction, or deep vein thromboses

15. Participant has a history of conditions that can cause coagulopathic conditions, including atrial fibrillation, heart valve surgery or replacement, hip or knee replacement, or clotting disorders

16. Participants using coagulation- or platelet-modifying therapies such as clotting factor products, emicizumab, desmopressin acetate, epsilon amino caproic acid, heparin and its derivatives, argatroban, desirudin, bivalirudin, dabigatran, apixaban, edoxaban, betrixaban

17. Participant has a history of chronic tobacco use or has ingested nicotine via smoking, vaping, smokeless tobacco, or nicotine patches in the past three months

18. Participant has consumed caffeine within the past 12 hours

19. Participant has received a blood transfusion within 30 days prior to study

20. Participant has a history of neurologic diseases or traumatic brain injury

21. Women of childbearing potential, not using adequate contraception as per investigator judgment or not willing to comply with contraception for the duration of the study

22. Females who are pregnant, lactating or menstruating

23. Participant has any other significant disease or disorder which, in the opinion of the Investigator, may either put the participants are risk because of participation in the trial, or may influence the result of the trial, or the participant's ability to participate in the trial