# Proof of concept and feasibility in humans for pulsed ultrasound treatment to reduce inflammation and risk of AKI

> **NIH NIH R01** · UNIVERSITY OF VIRGINIA · 2024 · $311,538

## Abstract

Abstract
This clinical study proposal is being submitted in response to PAS-20-160 "Small R01s for Clinical Trials
Targeting Diseases within the Mission of NIDDK, which does not require preliminary data." in order to
address unmet needs in the acute kidney injury (AKI) field through a novel approach to ameliorate
immunopathology. AKI is a devastating clinical disorder and major health burden with no FDA approved
drugs for its prevention or treatment. Current barriers to successful treatment of AKI include off-target effects
of pharmacological agents, the invasive nature of certain therapies, a lack of appropriate animal models of
AKI that faithfully mimic human disease, and incomplete understanding of the pathophysiology of AKI. Since
our first report that a simple ultrasound (US)-based protocol reduced tissue and systemic inflammation and
prevented ischemia-reperfusion injury (IRI) in mice, we have demonstrated that this effect was dependent
on the spleen and functional α7-nicotinic acetylcholine receptors (α7nAChRs). These observations are
consistent with the hypothesis that US treatment activated the splenic inflammatory reflex, a neuro-
immunomodulatory pathway. Our studies indicate that the protective effect of US depends on an intact
spleen, the presence of T cells and bone marrow-derived α7nAChRs, and splenic innervation. US has
wwoptogenetics we have mapped the neurocircuit of the inflammatory reflex pathway and are now poised
to determine the effect in human AKI. In particular we will examine the effect of pulsed US on AKI induced
from cardiac surgery, due to the importance of inflammation in this disorder. This clinical study proposal is
intended to build upon and translate our preclinical studies over the past several years and is designed to
test the hypothesis that pulsed US stimulation can be used effectively in human subjects to control
pathogenic inflammatory responses through the stimulation of the cholinergic anti-inflammatory reflex
pathway. Aim 1 will test the hypothesis that pulsed US stimulation within the FDA-approved limits of
diagnostic ultrasonography is able to attenuate inflammation and alter the composition of immune cells
collected from healthy subjects. Subjects will receive US targeting the splenic nerve and then immune cells
will be isolated from their blood and treated ex vivo withw inflammatory stimuli to test their inflammatory
capacity in comparison to immune cells collected prior to US. Aim 2 will test, in a pilot study, the hypothesis
that prior ultrasound stimulation in a population at risk for the development of AKI, i.e. adults undergoing
cardiac surgery, will reduce systemic inflammation and innate immunity. Additional goals will be to acertain
if there are any side effects as well as to obtain necessary data and develop the necessary elements to
conduct a large rmulticenter clinical trial to determine the efficacy of pulsed ultrasound to prevent AKI.

## Key facts

- **NIH application ID:** 10980616
- **Project number:** 1R01DK137937-01A1
- **Recipient organization:** UNIVERSITY OF VIRGINIA
- **Principal Investigator:** Mark Douglas Okusa
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $311,538
- **Award type:** 1
- **Project period:** 2024-09-15 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10980616

## Citation

> US National Institutes of Health, RePORTER application 10980616, Proof of concept and feasibility in humans for pulsed ultrasound treatment to reduce inflammation and risk of AKI (1R01DK137937-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10980616. Licensed CC0.

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