Optimizing Ultrasound-induced Anti-inflammation in Human Subjects

NCT05685108 | Recruiting DMC FDA Device

• 1 other identifier: HSR220029
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy Subjects

Keywords

Cholinergic anti-inflammatory pathway; Vagus nerve; Cytokines; Neuromodulation

Outcome Measures

Primary Outcomes (2)

• Change in concentrations of immune cells and cytokines depending on ultrasound stimulation intensity

  The primary outcome is to determine ultrasound intensities that have a biological effect on immune cells measured as a statistically significant change in the level of cytokines produced by immune cells. White blood cells will be isolated from peripheral blood and treated ex vivo with inflammatory stimuli to evaluate their capacity for cytokine production. The cytokines to be measured are (all will be measured in pg/ml): sCD40L; EGF; Eotaxin; FGF-2; FLT-3L; Fractalkine; G-CSF; GM-CSF; GRO; IFNα2; IFNy; IL-1α; IL-1β; IL-1Ra; IL-2; IL-3; IL-4; IL-5; IL-6; IL-7; IL-8; IL-9; IL-10; IL-12p40; IL-12p70; IL-13; IL-15; IL-17A; IL-17E; IL-17F; IL-18; IL-22; IL-27; IP-10; MCP-1; MCP-3; M-CSF; MDC; MIG; MIP-1α; MIP-1β; PDGF-AA; PDGF-AB/BB; TGFα; TNFα; TNFβ; VEGF-A.

  Immune cells will be stimulated and assessed prior to and within 24 to 48 hours post-ultrasound treatment. Results of Luminex analysis of the pre- and post-ultrasound stimulation supernatants will be compared to quantify the impacts of the treatment.

• Change in concentrations of immune cells and cytokines depending on ultrasound stimulation site

  The primary outcome is to determine the effects of spleen-targeted versus cervical vagus-targeted ultrasound stimulation on the inflammatory capacity of immune cells. This will be measured by stimulating white blood cells from peripheral blood ex vivo with inflammatory stimuli to evaluate their capacity for cytokine production. The cytokines to be measured are (all will be measured in pg/ml): sCD40L; EGF; Eotaxin; FGF-2; FLT-3L; Fractalkine; G-CSF; GM-CSF; GRO; IFNα2; IFNy; IL-1α; IL-1β; IL-1Ra; IL-2; IL-3; IL-4; IL-5; IL-6; IL-7; IL-8; IL-9; IL-10; IL-12p40; IL-12p70; IL-13; IL-15; IL-17A; IL-17E; IL-17F; IL-18; IL-22; IL-27; IP-10; MCP-1; MCP-3; M-CSF; MDC; MIG; MIP-1α; MIP-1β; PDGF-AA; PDGF-AB/BB; TGFα; TNFα; TNFβ; VEGF-A.

  Immune cells will be stimulated and assessed prior to and within 24 to 48 hours post-ultrasound treatment. Results of Luminex analysis of the pre- and post-ultrasound stimulation supernatants will be compared to quantify the impacts of the treatment.

Secondary Outcomes (1)

• Distribution of immune cells

  The secondary outcome will be assessed before and max 48-hours after receiving ultrasound stimulation.

Other Outcomes (1)

• Participant comfort, experience, and new-onset sensations by questionnaire

  The outcome will be assessed immediately after, within 24 to 48 hours, and 2 weeks after receiving ultrasound stimulation

Study Arms (2)

Group 1

ACTIVE COMPARATOR

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.

Device: Ultrasound stimulation intensity

Group 2

ACTIVE COMPARATOR

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.

Device: Ultrasound stimulation site

Interventions

Ultrasound stimulation intensity 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 1

Ultrasound stimulation site 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.

Group 2

Eligibility Criteria

• Age: 25 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Virginia: lead

Study Sites (1)

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

Charlottesville, Virginia, 22903, United States

RECRUITING

Related Publications (4)

• 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.

  PMID: 28970585 BACKGROUND

• 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.

  PMID: 32508112 BACKGROUND

• 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.

  PMID: 25644106 BACKGROUND

• 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.

  PMID: 30862827 BACKGROUND

Study Officials

• Mark D. Okusa, MD, FASN

  University of Virginia

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Mark D. Okusa, MD, FASN

CONTACT

+14349242187; mdo7y@virginia.edu

Igor A. Shumilin, PhD

CONTACT

+14349249691; IAS2N@hscmail.mcc.virginia.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Division of Nephrology

Model Details: After screening, eligible participants will be assigned to one of the two groups and randomized to order of treatments.

Study Record Dates

• First Submitted: December 15, 2022
• First Posted: January 13, 2023
• Study Start: September 15, 2024
• Primary Completion: October 1, 2025
• Study Completion: October 1, 2025
• Last Updated: July 22, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)