Biological Effects of Ultrasound Insonification of the Spleen

Study Overview
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Brief Summary
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This is a seven-cohort, double-blinded, randomized, sham-controlled feasibility trial to determine whether organ-specific biological effects are achievable through selective ultrasound of the spleen utilizing low-energy insonification.

Detailed Description
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This study will consist of three study visits. At the screening visit, individuals will be asked to undergo a physical and neurological examination, a blood draw of 4 teaspoons, and a urine pregnancy test if of childbearing potential. The participants that clear study screening will be randomized to one of seven groups. The groups consist of: sham insonification at the hilum (connected probe or disconnected probe); half-powered insonification at the hilum; full-powered insonification at the hilum; sham insonification at the lower, middle, and upper spleen; half-powered insonification at the lower, middle, and upper spleen; and full-powered insonification at the lower, middle, and upper spleen. At the baseline visit, individuals will be asked to undergo a physical and neurological examination and a blood draw of 7 teaspoons before receiving ultrasound as per their assigned group. These individuals will then be asked to undergo a blood draw of 5 teaspoons at 1-hour and 2-hours after the ultrasound. Individuals will be asked to return 24 hours later for the follow-up visit, which will include a physical and neurological examination and a blood draw of 9 teaspoons. The blood samples collected before insonification, one hour after insonification, two hours after insonification, and twenty-four hours after insonification will be assessed for changes in biomarkers (substances in the body that indicate the status of a biological process or condition). These biomarkers include cytokines (proteins involved in the immune response), norepinephrine (chemical in the body that transmits signals), glucose (sugar in the blood), and blood cells that are involved in breathing, clotting, and the immune response. The study will be considered complete after completion of enrollment (10 participants in each group, for a study total of 70 participants), completion of study procedures by all participants, and the completion of analysis of identifiable study data.

Official Title
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Biological Effects of Ultrasound Insonification of the Spleen

Conditions
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Healthy Volunteer

Intervention / Treatment
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* Device: Ultrasound
* Device: Sham Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals between 18 and 45 years of age Individuals without physical disabilities or conditions/diseases that may make them incapable of undergoing the study procedures or otherwise places them at a greater risk of harm Individuals without significant past medical or surgical histories that would render them at a greater risk of harm Individuals that are considered English Proficient due to the study requirements to follow verbal commands during the ultrasound session 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 Individuals able to attend all study visits at approximately the same time of day (i.e., 8 - 12 pm) Individuals that are able to comprehend the study goals and procedures, and are able to provide informed consent for participation Exclusion Criteria: Individuals participating in another research study that may affect the conduct or results of this study Individuals considered substantially overweight or obese via body mass index (≥ 29) 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) a 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 history of thrombosis or bleeding disorders stage III-IV pressure ulcers sickle cell anemia or other anemia syndromes monocytosis thrombocytopenia diagnosed with fever of unknown origin (FUO) previously or currently implanted vagus nerve stimulator previously or currently implanted spinal cord stimulator other chronically-implanted electronic medical device history of seizures history of cancer Individuals who have taken any of the following medications within one week of receiving ultrasound delivery: anti-coagulant (Coumadin, Xarelto) anti-platelet (aspirin, Plavix) 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 Individuals with a substance abuse (alcoholism or other) problem Individuals that consumed alcohol within 4 days of the baseline visit Individuals currently using or have used tobacco or nicotine products within the past 1 month Individuals currently using or have used recreational drugs within the past 1 month Pregnant women Prisoners

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: After a screened individual is deemed eligible for continued participation, a study investigator will enter the participant's information into a randomization portal in order to receive the group assignment.
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Group 1<br>Individuals will receive sham non-imaging mode ultrasound (control group) delivered to just the spleen's hilum (area of spleen that allows passage of blood vessels, lymphatic vessels, and nerves). | Device: Sham Ultrasound<br>* A specially designed ultrasound will be placed against the abdomen of an individual in order to administer sham insonification to the spleen.<br>|
| Experimental: Group 2<br>Individuals will receive half-powered non-imaging mode ultrasound delivered to just the spleen's hilum (area of spleen that allows passage of blood vessels, lymphatic vessels, and nerves). | Device: Ultrasound<br>* A specially designed ultrasound will be placed against the abdomen of an individual in order to administer low levels of insonification to the spleen.<br>|
| Experimental: Group 3<br>Individuals will receive full-powered non-imaging mode ultrasound delivered to just the spleen's hilum (area of spleen that allows passage of blood vessels, lymphatic vessels, and nerves). | Device: Ultrasound<br>* A specially designed ultrasound will be placed against the abdomen of an individual in order to administer low levels of insonification to the spleen.<br>|
| Sham Comparator: Group 4<br>Individuals will receive sham non-imaging mode ultrasound (control group) delivered to the lower, middle, and upper spleen based on the spleen's size. | Device: Sham Ultrasound<br>* A specially designed ultrasound will be placed against the abdomen of an individual in order to administer sham insonification to the spleen.<br>|
| Experimental: Group 5<br>Individuals will receive half-powered non-imaging mode ultrasound delivered to the lower, middle, and upper spleen based on the spleen's size. | Device: Ultrasound<br>* A specially designed ultrasound will be placed against the abdomen of an individual in order to administer low levels of insonification to the spleen.<br>|
| Experimental: Group 6<br>Individuals will receive full-powered non-imaging mode ultrasound delivered to the lower, middle, and upper spleen based on the spleen's size. | Device: Ultrasound<br>* A specially designed ultrasound will be placed against the abdomen of an individual in order to administer low levels of insonification to the spleen.<br>|
| Sham Comparator: Group 7<br>Individuals will receive sham non-imaging mode ultrasound with a disconnected probe (control group) delivered to just the spleen's hilum (area of spleen that allows passage of blood vessels, lymphatic vessels, and nerves). | Device: Sham Ultrasound<br>* A specially designed ultrasound will be placed against the abdomen of an individual in order to administer sham insonification to the spleen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-inflammatory Response | The primary outcome to determine whether diagnostic-level ultrasound to the spleen has a biological effect is measured as a statistically significant change in the level of biomarkers associated with the inflammatory response following delivery of ultrasound. | The primary outcome will be assessed before ultrasound and at 1-hour, 2-hours, and 24-hours after receiving ultrasound. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transient Tissue Displacement | The secondary outcome to determine whether ultrasound delivery to the spleen leads to transient tissue displacement that is correlated to organ-specific biological effects is measured as a statistically significant correlation between the magnitude of transient displacement and the biological effects. | The secondary outcome will be assessed approximately every 15 seconds during the approximately 10-minute ultrasound. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Healthy Volunteer, Ultrasound, Insonification, Spleen