Ultrasound Stimulation for Inflammation and Healthy Subjects

Overseen By Igor A. Shumilin, PhD

Age: 18 - 65

Sex: Any

Trial Phase: Academic

Sponsor: University of Virginia

Must not be taking: Anti-inflammatories, Immunosuppressants, Anticoagulants, Antiplatelets

Disqualifiers: Cancer, Hypertension, Diabetes, Obesity, Autoimmune disorders, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 38

Duration: 4-8 weeks

40 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to explore whether ultrasound waves can trigger an anti-inflammatory response by targeting specific nerves, namely the splenic and cervical vagus nerves. Researchers are testing different ultrasound levels to determine which best reduces inflammation without medication. The study seeks healthy volunteers who have no chronic conditions and are not taking any medications that affect inflammation. As an unphased trial, it offers participants a unique opportunity to contribute to groundbreaking research on reducing inflammation without medication.

What prior data suggests that this ultrasound stimulation is safe for healthy subjects?

Research shows that ultrasound therapy is generally safe and easy to handle. Studies have found that low-intensity pulsed ultrasound (LIPUS) can help reduce swelling in various conditions. Clinical trials have successfully used it to decrease inflammation. This method is considered affordable, safe, and easy to use.

Other studies tested ultrasound on animals, where it reduced swelling without causing serious side effects. While these results are encouraging, it's important to remember that what works in animals doesn't always work the same way in humans.

Overall, current evidence suggests that using ultrasound to reduce inflammation is a safe option. The treatment has been used in different situations without major problems. However, like any treatment, rare reactions might occur, so discussing any concerns with the trial team is always a good idea. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about using ultrasound stimulation for inflammation because it offers a non-invasive way to potentially reduce inflammation by targeting the body's internal systems. Unlike standard anti-inflammatory treatments that often rely on medications like NSAIDs or corticosteroids, this method uses pulsed ultrasound to stimulate specific areas such as the splenic hilum and cervical vagus nerve. This innovative approach could lead to fewer side effects and more precise control over inflammation, making it a promising alternative to traditional drug therapies.

What evidence suggests that ultrasound-induced anti-inflammation could be effective for reducing inflammation?

Research has shown that low-intensity ultrasound can reduce swelling and aid healing for various conditions. This trial will explore different ultrasound treatments, including those with varying mechanical indices, to assess their effects on inflammation. Studies have found that ultrasound can boost the body's immune system, helping manage swelling. For instance, research on animals demonstrated that ultrasound improved recovery in rats with spinal cord injuries by reducing swelling. Another study discovered that ultrasound can trigger the release of substances that help control swelling. Overall, these findings suggest that ultrasound might be a promising way to manage swelling in humans. ^{3 6 7 8 9}

Who Is on the Research Team?

Mark D. Okusa, MD, FASN

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for healthy adults aged 25-50 who speak English, can follow the study's rules, and will be available throughout. They must have normal blood counts and organ function. People with bleeding disorders, heart issues like arrhythmias or high blood pressure needing multiple drugs, recent drug use (anti-inflammatories, anticoagulants), infections, allergies to ultrasound gel, implants like pacemakers or a history of certain surgeries cannot join.

Inclusion Criteria

Provision of signed and dated informed consent form

Male or female, aged 25-50 years

Able to comprehend the study goals and procedures, stated willingness to comply with all study procedures, and availability for the duration of the study

Exclusion Criteria

History of bleeding disorder

History of arrhythmia (e.g., clinically significant bradycardia, atrial flutter, atrial fibrillation, ventricular arrhythmias)

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

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive pulsed ultrasound stimulation targeting the splenic nerve or the cervical vagus nerve at different intensities

4-8 weeks

Multiple visits with a minimum of 14 days between each stimulation

Follow-up

Participants are monitored for changes in immune cell concentrations and cytokine levels post-ultrasound treatment

2-4 weeks

Assessments within 24 to 48 hours post-treatment

What Are the Treatments Tested in This Trial?

Interventions

• Ultrasound-induced Anti-inflammation

Trial Overview The study tests if pulsed ultrasound aimed at nerves in the neck or near the spleen can reduce inflammation in healthy people. It checks two things: how intense the ultrasound should be and exactly where it should target.

How Is the Trial Designed?

Group I: Group 2 Active Control 1 Intervention

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 II: Group 1 Active Control 1 Intervention

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.

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5660123/

Low-Intensity Ultrasound-Induced Anti-inflammatory Effects ... Background: Low-intensity ultrasound (LIUS) was shown to be beneficial in mitigating inflammation and facilitating tissue repair in various pathologies.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05685108

NCT05685108 | Optimizing Ultrasound-induced Anti- ... Recently, the use of pulsed ultrasonic waves to modulate the neuroimmune pathway has gained interest due to its potential in treating inflammatory disorders non ...

3. nature.com nature.com/articles/s41598-022-07114-6

Ultrasound stimulation improves inflammatory resolution ... This study showed that low-intensity US stimulation could induce the recovery of hindlimb dyskinesia in rats with a damaged spinal cord. Two US ...

4. elifesciences.org elifesciences.org/reviewed-preprints/89512v2

Pulsed ultrasound promotes secretion of anti-inflammatory ... This study illuminates the effects of ultrasound-induced extracellular vesicle interactions with macrophages. It provides solid data offering ...

5. frontiersin.org frontiersin.org/journals/medicine/articles/10.3389/fmed.2024.1292473/full

Effectiveness of low-intensity pulsed ultrasound on ... Numerous research studies have validated the effectiveness of low-intensity pulsed ultrasound (LIPUS) in OA treatment.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11337181/

Ultrasound therapy for pain reduction in musculoskeletal ... The current evidence supports the effectiveness of ultrasound therapy in reducing pain and aiding rehabilitation for knee conditions.

7. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/08/NCT05685108/Prot_SAP_000.pdf

Optimizing Ultrasound-induced Anti-inflammation in ... DATA AND SAFETY MONITORING PLAN ... treatment conditions to assess the relative impact of each ultrasound stimulation protocol.

8. sciencedirect.com sciencedirect.com/science/article/pii/S106345841200026X

Anti-inflammatory effect of low intensity ultrasound (LIUS) ... In this study, the effect of low intensity ultrasound (LIUS) applied to an adjuvant-induced arthritic rat model on the synovium was investigated. Design.

9. qims.amegroups.org qims.amegroups.org/article/view/55363/html

intensity pulsed ultrasound in inflammation - Xu In a clinical trial, LIPUS has been shown to alleviate inflammatory responses efficiently. As a cheap, safe, and convenient physical method, LIPUS is promising ...