Biological Effects of Ultrasound Insonification of the Spleen

NCT ID: NCT03548116

Last Updated: 2021-12-14

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

137 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-23

Study Completion Date

2022-11-30

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.

Conditions

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Healthy Volunteer

Keywords

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Healthy Volunteer Ultrasound Insonification Spleen

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

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.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

DOUBLE

Participants Investigators
The study participants will be blinded to their group assignment for the entire duration of the study. The study investigators will also be blinded to participant assignments on this study, except for the investigators performing the ultrasound procedure, co-investigators randomizing the participants, and co-investigators involved in the study's monitoring.

Study Groups

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Group 1

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).

Group Type SHAM_COMPARATOR

Sham Ultrasound

Intervention Type DEVICE

A specially designed ultrasound will be placed against the abdomen of an individual in order to administer sham insonification to the spleen.

Group 2

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).

Group Type EXPERIMENTAL

Ultrasound

Intervention Type DEVICE

A specially designed ultrasound will be placed against the abdomen of an individual in order to administer low levels of insonification to the spleen.

Group 3

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).

Group Type EXPERIMENTAL

Ultrasound

Intervention Type DEVICE

A specially designed ultrasound will be placed against the abdomen of an individual in order to administer low levels of insonification to the spleen.

Group 4

Individuals will receive sham non-imaging mode ultrasound (control group) delivered to the lower, middle, and upper spleen based on the spleen's size.

Group Type SHAM_COMPARATOR

Sham Ultrasound

Intervention Type DEVICE

A specially designed ultrasound will be placed against the abdomen of an individual in order to administer sham insonification to the spleen.

Group 5

Individuals will receive half-powered non-imaging mode ultrasound delivered to the lower, middle, and upper spleen based on the spleen's size.

Group Type EXPERIMENTAL

Ultrasound

Intervention Type DEVICE

A specially designed ultrasound will be placed against the abdomen of an individual in order to administer low levels of insonification to the spleen.

Group 6

Individuals will receive full-powered non-imaging mode ultrasound delivered to the lower, middle, and upper spleen based on the spleen's size.

Group Type EXPERIMENTAL

Ultrasound

Intervention Type DEVICE

A specially designed ultrasound will be placed against the abdomen of an individual in order to administer low levels of insonification to the spleen.

Group 7

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).

Group Type SHAM_COMPARATOR

Sham Ultrasound

Intervention Type DEVICE

A specially designed ultrasound will be placed against the abdomen of an individual in order to administer sham insonification to the spleen.

Interventions

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Ultrasound

A specially designed ultrasound will be placed against the abdomen of an individual in order to administer low levels of insonification to the spleen.

Intervention Type DEVICE

Sham Ultrasound

A specially designed ultrasound will be placed against the abdomen of an individual in order to administer sham insonification to the spleen.

Intervention Type DEVICE

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
Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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General Electric

INDUSTRY

Sponsor Role collaborator

John Pellerito

OTHER

Sponsor Role lead

Responsible Party

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John Pellerito

Vice Chairman of Education, Department of Radiology; Director, Peripheral Vascular Laboratory and the Body Imaging Fellowship Program

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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John Pellerito, MD

Role: PRINCIPAL_INVESTIGATOR

Northwell Health

Locations

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Northwell Health's The Feinstein Institute for Medical Research

Manhasset, New York, United States

Site Status

Countries

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United States

References

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Koopman FA, Chavan SS, Miljko S, Grazio S, Sokolovic S, Schuurman PR, Mehta AD, Levine YA, Faltys M, Zitnik R, Tracey KJ, Tak PP. Vagus nerve stimulation inhibits cytokine production and attenuates disease severity in rheumatoid arthritis. Proc Natl Acad Sci U S A. 2016 Jul 19;113(29):8284-9. doi: 10.1073/pnas.1605635113. Epub 2016 Jul 5.

Reference Type BACKGROUND
PMID: 27382171 (View on PubMed)

Zeng W, Pirzgalska RM, Pereira MM, Kubasova N, Barateiro A, Seixas E, Lu YH, Kozlova A, Voss H, Martins GG, Friedman JM, Domingos AI. Sympathetic neuro-adipose connections mediate leptin-driven lipolysis. Cell. 2015 Sep 24;163(1):84-94. doi: 10.1016/j.cell.2015.08.055.

Reference Type BACKGROUND
PMID: 26406372 (View on PubMed)

Parker JL, Cameron T. Technology for Peripheral Nerve Stimulation. Prog Neurol Surg. 2015;29:1-19. doi: 10.1159/000434651. Epub 2015 Sep 4.

Reference Type BACKGROUND
PMID: 26394391 (View on PubMed)

Birk DM, Yin D, Slavin KV. Regulation of Peripheral Nerve Stimulation Technology. Prog Neurol Surg. 2015;29:225-37. doi: 10.1159/000434674. Epub 2015 Sep 4.

Reference Type BACKGROUND
PMID: 26394389 (View on PubMed)

Tracey KJ. Physiology and immunology of the cholinergic antiinflammatory pathway. J Clin Invest. 2007 Feb;117(2):289-96. doi: 10.1172/JCI30555.

Reference Type BACKGROUND
PMID: 17273548 (View on PubMed)

Martelli D, McKinley MJ, McAllen RM. The cholinergic anti-inflammatory pathway: a critical review. Auton Neurosci. 2014 May;182:65-9. doi: 10.1016/j.autneu.2013.12.007. Epub 2013 Dec 24.

Reference Type BACKGROUND
PMID: 24411268 (View on PubMed)

Juan EJ, Gonzalez R, Albors G, Ward MP, Irazoqui P. Vagus Nerve Modulation Using Focused Pulsed Ultrasound: Potential Applications and Preliminary Observations in a Rat. Int J Imaging Syst Technol. 2014 Mar 1;24(1):67-71. doi: 10.1002/ima.22080.

Reference Type BACKGROUND
PMID: 25165410 (View on PubMed)

Goggins E, Inoue H, Okusa MD. Neuroimmune Control of Inflammation in Acute Kidney Injury and Multiorgan Dysfunction. J Am Soc Nephrol. 2025 Jul 7. doi: 10.1681/ASN.0000000813. Online ahead of print.

Reference Type DERIVED
PMID: 40622772 (View on PubMed)

Related Links

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https://commonfund.nih.gov/sparc

Stimulating Peripheral Activity to Relieve Conditions (SPARC)

http://iopscience.iop.org/article/10.1088/1742-6596/581/1/012003/meta

Ultrasonic Stimulation of Peripheral Nervous Tissue

Other Identifiers

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17-0859

Identifier Type: -

Identifier Source: org_study_id