Optimizing Ultrasound-induced Anti-inflammation in Human Subjects

NCT ID: NCT05685108

Last Updated: 2025-07-22

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

RECRUITING

Clinical Phase

NA

Total Enrollment

40 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-09-15

Study Completion Date

2025-10-31

Brief Summary

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This is a feasibility study to determine whether pulsed ultrasound stimulation targeting the splenic nerve or the cervical vagus nerve can elicit an anti-inflammatory immune response in healthy volunteers.

Detailed Description

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Recent advances have shown that neural pathways are able to regulate immunity and inflammation. The cholinergic anti-inflammatory pathway is a well-characterized neural circuit that consists of the vagus nerve to spleen circuit, which has been stimulated with implantable devices to improve autoimmune conditions such as rheumatoid arthritis.

Recently, the use of pulsed ultrasonic waves to modulate the neuroimmune pathway has gained interest due to its potential in treating inflammatory disorders non-invasively. This study is designed to test the hypothesis that pulsed ultrasound stimulation can be used effectively in human subjects to control pathogenic inflammatory responses. The overall goal of this project is to determine which, if any, ultrasound stimulation protocols are able to restrict the inflammatory response of immune cells collected from healthy subjects post-ultrasound stimulation.

Four different levels of ultrasound intensity ("doses") will be tested in this study to determine the dose(s) capable of producing an anti-inflammatory effect. The doses will be defined in terms of mechanical index and each subject will receive two different doses of ultrasound. In addition, the study will investigate the efficacy of cervical vagus (neck)-targeted ultrasound, given that it may have an effect similar to spleen-targeted ultrasound through upstream vagus nerve modulation.

Conditions

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Healthy Subjects

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

After screening, eligible participants will be assigned to one of the two groups and randomized to order of treatments.
Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

NONE

Study Groups

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Group 1

In Subgroup 1, individuals will receive pulsed ultrasound with a mechanical index of 0.6 and 1.4 delivered to the splenic hilum.

In Subgroup 2, individuals will receive pulsed ultrasound with a mechanical index of 1.0 and 1.8 delivered to the splenic hilum.

In Subgroup 3, individuals will receive sham treatment and pulsed ultrasound with a mechanical index of 1.4 delivered to the splenic hilum.

In all Subgroups, the two doses will be administered in separate visits with min. 14 days between each stimulation.

Group Type ACTIVE_COMPARATOR

Ultrasound stimulation intensity

Intervention Type DEVICE

A clinical ultrasound transducer will be placed against the abdomen or neck of an individual in order to administer insonification to the splenic nerve.

Group 2

Individuals will receive pulsed ultrasound with a mechanical index of 1.4 delivered to the splenic hilum and the cervical vagus nerve. The two doses will be administered in separate visits with min. 14 days between each stimulation.

Group Type ACTIVE_COMPARATOR

Ultrasound stimulation site

Intervention Type DEVICE

A clinical ultrasound transducer will be placed against the abdomen or neck of an individual in order to administer insonification to the splenic nerve and the cervical vagus nerve.

Interventions

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Ultrasound stimulation intensity

A clinical ultrasound transducer will be placed against the abdomen or neck of an individual in order to administer insonification to the splenic nerve.

Intervention Type DEVICE

Ultrasound stimulation site

A clinical ultrasound transducer will be placed against the abdomen or neck of an individual in order to administer insonification to the splenic nerve and the cervical vagus nerve.

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* Male or female, aged 25-50 years
* Provision of signed and dated informed consent form
* Able to comprehend the study goals and procedures, stated willingness to comply with all study procedures, and availability for the duration of the study
* Considered English proficient so that the subject can follow verbal commands during the ultrasound procedure
* In good general health, as evidenced by medical history
* Laboratory results indicating normal blood count and adequate organ function
* Agreement to adhere to Lifestyle Considerations throughout study duration.

Exclusion Criteria

* Chronic medical conditions, including cancer (in remission or active cancer), cerebrovascular disease, chronic kidney disease, heart conditions (such as heart failure, coronary artery disease, cardiomyopathies), lung disease, liver disease, hypertension, diabetes mellitus type 1 and 2, human immunodeficiency virus infection, primary immunodeficiencies, solid organ or hematopoietic cell transplantation, tuberculosis, and cystic fibrosis, autoimmune disorders (e.g., rheumatoid arthritis, inflammatory bowel disease), sickle cell anemia or other anemia syndromes
* Mean systolic and diastolic blood pressure values during screening of ≥160 and ≥100 mm Hg, respectively, hypertension on non-selective beta-blockers and/or alpha-methyl dopa, or hypertension requiring more than two anti-hypertension medications
* Obesity (body mass index ≥30 kg/m2)
* Use of anti-inflammatory or immunomodulatory medication, such as non- steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, or other immunosuppressants, within one week of receiving ultrasound delivery
* Use of anticoagulant drugs (e.g., coumadin, direct oral anticoagulants) or antiplatelet drugs (e.g., aspirin, clopidogrel) within one week of receiving ultrasound delivery
* Pregnancy, breastfeeding, or planning to become pregnant during the study
* Active bacterial or viral infection; febrile illness within 2 weeks of receiving ultrasound delivery
* Known allergic reactions to ultrasound gel
* Treatment with another investigational drug or other intervention within 1 month of receiving ultrasound delivery
* Any vaccination received within 1 month of receiving ultrasound delivery
* Current smoker or nicotine use within 2 weeks of receiving ultrasound delivery
* Use of recreational drugs within 2 weeks of receiving ultrasound delivery
* History of arrythmia (e.g., clinically significant bradycardia, atrial flutter, atrial fibrillation, ventricular arrythmias)
* History of deep vein thrombosis or pulmonary embolism
* History of bleeding disorder
* History of seizure
* History of unilateral or bilateral vagotomy
* Participants with an implantable medical device, such as pacemaker, hearing aid implant, or any implanted electronic device
* Surgery or traumatic injury (e.g., visceral injury, cerebral injury) in the past 3 months
* Prior surgery on thyroid or parathyroid glands, esophagus, stomach, or spleen
* Participant is considered by the Investigator, after reviewing medical and psychiatric history, physical examination, and laboratory evaluations, to be unsuitable for any other reason that may either place the patient at increased risk during participation or interfere with the interpretation of the study. outcomes.
Minimum Eligible Age

25 Years

Maximum Eligible Age

50 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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University of Virginia

OTHER

Sponsor Role lead

Responsible Party

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Mark Okusa, MD

Chief, Division of Nephrology

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Mark D. Okusa, MD, FASN

Role: PRINCIPAL_INVESTIGATOR

University of Virginia

Locations

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University of Virginia, Division of Nephrology; Center for Immunity, Inflammation & Regenerative Medicine

Charlottesville, Virginia, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Mark D. Okusa, MD, FASN

Role: CONTACT

+14349242187

Igor A. Shumilin, PhD

Role: CONTACT

+14349249691

Facility Contacts

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Mark D. Okusa, MD, FASN

Role: primary

434-924-2187

Igor A. Shumilin, PhD

Role: backup

+14349249691

References

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Okusa MD, Rosin DL, Tracey KJ. Targeting neural reflex circuits in immunity to treat kidney disease. Nat Rev Nephrol. 2017 Nov;13(11):669-680. doi: 10.1038/nrneph.2017.132. Epub 2017 Oct 3.

Reference Type BACKGROUND
PMID: 28970585 (View on PubMed)

Cai J, Nash WT, Okusa MD. Ultrasound for the treatment of acute kidney injury and other inflammatory conditions: a promising path toward noninvasive neuroimmune regulation. Am J Physiol Renal Physiol. 2020 Jul 1;319(1):F125-F138. doi: 10.1152/ajprenal.00145.2020. Epub 2020 Jun 8.

Reference Type BACKGROUND
PMID: 32508112 (View on PubMed)

Gigliotti JC, Huang L, Bajwa A, Ye H, Mace EH, Hossack JA, Kalantari K, Inoue T, Rosin DL, Okusa MD. Ultrasound Modulates the Splenic Neuroimmune Axis in Attenuating AKI. J Am Soc Nephrol. 2015 Oct;26(10):2470-81. doi: 10.1681/ASN.2014080769. Epub 2015 Feb 2.

Reference Type BACKGROUND
PMID: 25644106 (View on PubMed)

Cotero V, Fan Y, Tsaava T, Kressel AM, Hancu I, Fitzgerald P, Wallace K, Kaanumalle S, Graf J, Rigby W, Kao TJ, Roberts J, Bhushan C, Joel S, Coleman TR, Zanos S, Tracey KJ, Ashe J, Chavan SS, Puleo C. Noninvasive sub-organ ultrasound stimulation for targeted neuromodulation. Nat Commun. 2019 Mar 12;10(1):952. doi: 10.1038/s41467-019-08750-9.

Reference Type BACKGROUND
PMID: 30862827 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

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HSR220029

Identifier Type: -

Identifier Source: org_study_id

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