Ultrasound Cavitation Therapy for Peripheral Arterial Disease

Overseen By Jonathan Lindner, MD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Virginia

Disqualifiers: Severe heart failure, Pregnancy, others

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

Approved in 4 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 18 days

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ultrasound cavitation therapy to heal stubborn ulcers caused by peripheral arterial disease (PAD), which affects blood flow in the legs. The researchers aim to determine if sound waves with tiny bubbles can speed up healing and improve blood flow in the affected areas. Patients with PAD who have had a non-healing ulcer for over three months might be suitable for this study. Participants will either receive cavitation therapy or join a control group without the treatment to compare results. As an unphased trial, this study allows patients to contribute to innovative research that could lead to new treatment options for PAD-related ulcers.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

What prior data suggests that ultrasound cavitation therapy is safe for treating peripheral arterial disease?

Research has shown that ultrasound cavitation therapy, used to treat peripheral arterial disease (PAD), is generally safe and well-tolerated by patients. One study on patients with PAD symptoms found that this therapy did not cause major side effects. Most patients experienced improved blood flow and oxygen levels in their tissues, which are positive indicators for healing.

Ultrasound therapy has also been studied for other uses, such as reducing fat, and has been found safe in those cases as well. Overall, these findings suggest that ultrasound cavitation therapy is a safe option for people with PAD. However, discussing potential risks and benefits with a healthcare provider remains important. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Ultrasound Cavitation Therapy is unique because it uses sound waves to target and break down blockages in the arteries, which is different from traditional treatments like medications or surgical procedures. Unlike standard methods that might involve invasive techniques, this therapy offers a non-invasive option that could reduce recovery time and potential complications. Researchers are excited because this approach has the potential to improve blood flow more efficiently and with less discomfort for patients suffering from Peripheral Arterial Disease.

What evidence suggests that ultrasound cavitation therapy is effective for peripheral arterial disease?

Research has shown that ultrasound cavitation therapy, which participants in this trial may receive, can improve blood flow in individuals with blocked arteries in their legs. This improvement is crucial for those with peripheral arterial disease (PAD) because enhanced blood flow aids in healing wounds and ulcers. The therapy uses sound waves to create tiny bubbles that help clear the arteries. Studies also suggest that this treatment is safe and can enhance blood flow in the limbs, making it a promising option for treating severe ulcers that resist healing due to PAD. ^{1 2 4 6 7}

Are You a Good Fit for This Trial?

This trial is for people with severe non-healing ulcers due to Peripheral Arterial Disease (PAD), specifically those who have not seen any improvement in the past 3 months. Participants must have a confirmed PAD diagnosis and be classified as having Critical Limb Ischemia. Those with major illnesses affecting the limb, pregnant or breastfeeding women, allergies to ultrasound contrast agents or PEG, unstable blood pressure, or upcoming amputation are excluded.

Inclusion Criteria

I have severe leg artery disease with a non-healing wound for over 3 months.

I have been diagnosed with PAD due to low ankle-brachial index or non-compressible vessels.

Exclusion Criteria

You are allergic to ultrasound contrast agents or polyethylene glycol.

I am expected to undergo amputation or a procedure to restore blood flow within the next month.

Pregnant or lactating females

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ultrasound cavitation therapy to treat non-healing ulcers

18 days

Follow-up

Participants are monitored for changes in wound granulation and tissue perfusion

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ultrasound Cavitation Therapy

Trial Overview

The study tests if using ultrasound to shake microbubble contrast agents can help heal severe ulcers caused by poor blood flow in PAD patients. It looks at whether this treatment speeds up healing and improves blood flow in the affected limb compared to usual care without these ultrasound effects.

How Is the Trial Designed?

Group I: Cavitation therapy Experimental Treatment 1 Intervention

Subjects treated with cavitation energy

Group II: Control Active Control 1 Intervention

Control subjects not treated with cavitation energy

Ultrasound Cavitation Therapy is already approved in European Union, United States, Canada for the following indications:

Approved in European Union as Ultrasonic Cavitation for:

• Body contouring
• Fat reduction
• Cellulite treatment

Approved in United States as Ultrasonic Cavitation for:

• Body contouring
• Fat reduction
• Cellulite treatment

Approved in Canada as Ultrasonic Cavitation for:

• Body contouring
• Fat reduction
• Cellulite treatment

Who Is Running the Clinical Trial?

University of Virginia

Lead Sponsor

Trials

802

Recruited

1,342,000+

Published Research Related to This Trial

Low-intensity pulsed ultrasound (LIPUS) and SonoVue alone do not harm human renal glomerular endothelial cells (HRGECs), but when used together, they significantly reduce cell proliferation and increase cell death.

The combination of LIPUS and SonoVue works by suppressing the ERK1/2 signaling pathway, and blocking this pathway with an inhibitor prevents the harmful effects, suggesting a specific mechanism of action for the cytotoxicity observed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-intensity pulsed ultrasound in combination with SonoVue induces cytotoxicity of human renal glomerular endothelial cells via repression of the ERK1/2 signaling pathway. Liu, X., Wang, B., Ding, H., et al.[2018]

The study found that using percutaneous catheter-delivered ultrasound energy combined with local paclitaxel delivery resulted in a significantly lower rate of restenosis (3.6%) and no target lesion revascularization (0%) at 6 months in patients with critical limb ischemia, compared to the control group which had a 21.4% restenosis rate and 10.7% TLR.

No adverse procedural events occurred in either group, indicating that the ultrasound and paclitaxel treatment is safe, with no myocardial infarctions, deaths, or amputations reported during the follow-up period.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Local Ultrasound to Enhance Paclitaxel Delivery After Femoral-Popliteal Treatment in Critical Limb Ischemia: The PACUS Trial. Gandini, R., Del Giudice, C.[2021]

The study explores a new approach to treating acute peripheral arterial thrombosis using contrast-enhanced sonothrombolysis, which combines ultrasound, ultrasound contrast agents (UCAs), and fibrinolytic agents, potentially improving thrombus dissolution compared to standard methods.

Using a porcine model, the research aims to enhance the effectiveness of thrombolytic therapy while addressing safety concerns, such as the risk of severe allergic reactions to UCAs, which could lead to better outcomes for patients with arterial occlusions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Contrast-enhanced sonothrombolysis in a porcine model of acute peripheral arterial thrombosis and prevention of anaphylactic shock. Nederhoed, JH., Slikkerveer, J., Meyer, KW., et al.[2014]

A review of ten studies on therapeutic ultrasound for lower limb musculoskeletal conditions found no high-quality evidence supporting its effectiveness, as most studies were of low quality.

None of the placebo-controlled trials demonstrated significant differences between actual ultrasound treatment and sham (fake) ultrasound, indicating that therapeutic ultrasound may not be an effective treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effectiveness of therapeutic ultrasound for musculoskeletal conditions of the lower limb: A literature review. Shanks, P., Curran, M., Fletcher, P., et al.[2011]

In a study involving 9 pigs with induced thrombus, the use of targeted microbubbles carrying urokinase combined with ultrasound significantly improved arterial blood flow compared to urokinase alone, with 3 out of 5 pigs showing improvement in the microbubble group.

The targeted microbubble approach also resulted in a significantly lower thrombus weight, indicating a more effective thrombolysis without any observed adverse effects, suggesting a promising new method for treating acute peripheral arterial occlusion.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intravenous Targeted Microbubbles Carrying Urokinase versus Urokinase Alone in Acute Peripheral Arterial Thrombosis in a Porcine Model. Nederhoed, JH., Ebben, HP., Slikkerveer, J., et al.[2018]

In preclinical studies with mice, optimized ultrasound (US) conditions significantly increased blood flow in the treated limb, with the best results achieved using high line density and longer pulse durations, leading to a 3- to 4-fold increase in perfusion.

In a first-in-human study, the same optimized US conditions combined with intravenous microbubble contrast resulted in over a 2-fold increase in calf muscle blood flow in both healthy individuals and patients with peripheral artery disease (PAD), suggesting a potential new therapy for PAD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Augmentation of Tissue Perfusion in Patients With Peripheral Artery Disease Using Microbubble Cavitation. Mason, OR., Davidson, BP., Sheeran, P., et al.[2021]

In a pilot study involving 12 patients with critical limb ischemia, the use of low-frequency, high-intensity ultrasound followed by balloon angioplasty achieved a high primary patency rate of 95% at 6 months, indicating effective treatment for calcified infrapopliteal lesions.

The treatment was found to be safe, with no reported deaths, major amputations, or target vessel occlusions within 30 days, and complete ulcer healing was observed in all patients by the 6-month follow-up.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Six-Month Angiographic and Clinical Outcomes of Therapeutic Ultrasound Pretreatment Associated With Plain Balloon Angioplasty for Below-the-Knee Lesions in Patients With Critical Limb Ischemia: A Prospective, Single-Center Pilot Study. Del Giudice, C., Gandini, R.[2022]

In a study involving 40 patients with atherosclerotic lesions, low-dose ultrasound treatment applied locally to ischemic leg tissues resulted in improved peripheral circulation and microcirculation.

The treatment also positively affected hemocoagulation, suggesting that low-dose ultrasound may enhance blood flow and clotting factors in patients with vascular issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The ultrasonic therapy of patients with arteriosclerosis obliterans of the vessels of the lower extremities]. Vashkevich, DL.[2006]

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This study aims at evaluating the histological and ultrastructural changes induced by ultrasound cavitation on the different cell components of human skin.

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Ultrasound Cavitation Therapy for Peripheral Arterial Disease

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This literature review aims to examine the mechanisms of ultrasound-induced lipolysis and summarize current FDA-approved ultrasound therapies. It compares the ...

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TUS for patients with symptomatic PAD was safe and well tolerated. Most metrics of tissue perfusion and oxygenation improved, ...

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Safety and Efficacy of UltraShape Contour I Treatments to ...

Both preclinical and clinical studies have provided data to support the validity of the Contour I as a noninvasive fat reduction and body contouring treatment ...