Ultrasound Therapy for Cardiac Amyloidosis

(UTICA Trial)

Overseen By Sharmila Dorbala, MD

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Brigham and Women's Hospital

Disqualifiers: Heart disease, Valve issues, Lung disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 1 day

70 Participants Needed

Trial Summary

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 data supports the effectiveness of the treatment Sonotherapy, Ultrasound Therapy, Sonotherapy for Cardiac Amyloidosis?

Research shows that ultrasound therapy can enhance the breakdown of blood clots and improve blood flow, which might suggest potential benefits for heart conditions. Additionally, sonodynamic therapy has been shown to inhibit fibrogenesis (formation of fibrous tissue) in heart cells, which could be relevant for treating cardiac amyloidosis. ^{1 2 3 4 5}

How is ultrasound therapy different from other treatments for cardiac amyloidosis?

Ultrasound therapy is unique because it uses sound waves to create controlled biological effects noninvasively, which can interact with tissues in various ways, such as through thermal and non-thermal effects like cavitation (formation of bubbles) and acoustic streaming. This approach is different from traditional treatments as it does not require surgery or medication, offering a potentially safer and less invasive option for managing cardiac conditions. ^{4 6 7 8 9}

What is the purpose of this trial?

This is a prospective pilot clinical study of subjects with cardiac amyloidosis and control subjects without amyloidosis where we plan to evaluate changes in myocardial blood flow, systolic and diastolic function before and after sonotherapy.

Research Team

Sharmila Dorbala, MBBS, MPH

Principal Investigator

Brigham and Women's Hospital

Eligibility Criteria

This trial is for adults over 18 with AL cardiac amyloidosis in remission, or those over 65 with ATTR cardiac amyloidosis or as controls. Participants must have proof of heart involvement and be able to consent. Excluded are pregnant individuals, those with other heart diseases, severe heart failure, allergies to specific ultrasound contrast agents, low ejection fraction (<40%), pulmonary hypertension, history of stroke, extreme claustrophobia, severe lung disease or valve issues.

Inclusion Criteria

Willing and able to provide consent

I am over 18 for AL-CA, over 65 for ATTR-CA, or over 65 as a control.

My heart is affected by AL amyloidosis, confirmed by tests or scans.

Exclusion Criteria

I have atrial fibrillation and am not taking blood thinners.

I have been diagnosed with blocked heart arteries.

A blood clot inside the heart has been confirmed by a doctor.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo sonotherapy, which includes rest 2D echocardiography, rest N-13 ammonia or rubidium-82 perfusion PET, and Definity infusion with high mechanical index imaging

1 day

Follow-up

Participants are monitored for changes in myocardial blood flow, systolic and diastolic function after sonotherapy

4 weeks

Treatment Details

Interventions

• Sonotherapy

Trial Overview The study tests sonotherapy's effects on blood flow and heart function in patients with cardiac amyloidosis compared to control subjects without the condition. It's a forward-looking pilot study where participants undergo sonotherapy treatment and then have their myocardial blood flow and heart functions assessed before and after the therapy.

Participant Groups

Group I: Sonotherapy Experimental Treatment 1 Intervention

All participants will undergo sonotherapy

Who Is Running the Clinical Trial?

Brigham and Women's Hospital

Lead Sponsor

Trials

1,694

Recruited

14,790,000+

Findings from Research

Sonodynamic therapy (SDT) effectively inhibits fibrogenesis in rat cardiac fibroblasts, showing potential as a treatment to prevent cardiac fibrosis.

The mechanism of action involves the activation of the AKT/GSK3β pathway and the blocking of TGF-β1/SMAD3 signaling, which reduces cell proliferation and levels of fibrotic markers like α-SMA and COLI/III.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sonodynamic Therapy Inhibits Fibrogenesis in Rat Cardiac Fibroblasts Induced by TGF-β1. Guo, Y., Dong, Z., Shi, Y., et al.[2019]

Therapeutic ultrasound is widely used for treating soft tissue injuries, which are common in rheumatic conditions, but there is limited evidence supporting its effectiveness in clinical settings.

The lack of clear benefits may stem from various factors, including technical differences in ultrasound application, the complexity of soft tissue injuries, and methodological issues in existing studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic ultrasound in soft tissue lesions. Speed, CA.[2022]

Fibrinolytic therapy is effective in reopening blocked coronary arteries during heart attacks, which helps reduce mortality and preserve heart function, but it can lead to bleeding complications.

Using low-intensity, high-frequency ultrasound as an adjuvant therapy can significantly enhance the rate of clot breakdown without causing damage to the clot itself, potentially allowing for lower doses of lytic agents and improving treatment outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ultrasound enhancement of thrombolytic therapy: observations and mechanisms. Harpaz, D.[2019]

In a study of 15 patients with acute myocardial infarction, ultrasound thrombolysis successfully restored blood flow in 87% of cases, demonstrating its efficacy as a treatment method.

The procedure was safe, with no adverse effects reported during treatment, and it resulted in a low final residual stenosis of 20% after adjunct angioplasty, indicating effective thrombus disruption.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Analysis of coronary ultrasound thrombolysis endpoints in acute myocardial infarction (ACUTE trial). Results of the feasibility phase. Rosenschein, U., Roth, A., Rassin, T., et al.[2019]

Sonothrombolysis, which uses ultrasound to help dissolve blood clots in acute stroke treatment, shows promise as a new strategy, especially for patients who cannot use traditional clot-dissolving drugs.

Combining ultrasound with fibrinolytic agents and echo contrast agents enhances the effectiveness of clot dissolution, potentially leading to better recovery outcomes for stroke patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Therapeutic ultrasound of acute cerebral artery occlusion]. Nedelmann, M., Gerriets, T., Kaps, M.[2021]

Therapeutic ultrasound (US) offers a noninvasive method to induce controlled biological effects in various tissues, making it a promising tool in cardiology.

The review highlights the growing clinical applications of US, particularly for cardiac pacing and treating cardiovascular diseases, emphasizing its potential to improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic Ultrasound in Cardiovascular Medicine. Coiado, OC., Lowe, J., O'Brien, WD.[2020]

Ultrasound therapy significantly decreased blood pressure in patients with hypertension, indicating its potential as a non-invasive treatment option for managing high blood pressure.

The study involved 29 patients undergoing 10 ultrasound sessions, and the most effective results were observed with medium ultrasound doses (0.5-1.5 W/cm2) and application times of 4-9 minutes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[The influence of ultrasound therapy on patient's blood pressure subjected to activity ultrasound]. Ciejka, E., Wiechna, K.[2009]

Ultrasound therapy has been studied for over 50 years and can treat tissues through various mechanisms such as thermal effects, shockwaves, and cavitation, making it a versatile treatment option.

Recent advancements in ultrasound technology have led to the development of devices for a wide range of non-cancer clinical applications, highlighting its potential to significantly improve patient care in various medical fields.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Emerging non-cancer applications of therapeutic ultrasound. O'Reilly, MA., Hynynen, K.[2018]

Ultrasound has shown potential as a therapeutic tool in cardiovascular diseases, with applications including thrombolysis, drug delivery, and local gene transfer, based on extensive in vitro and animal studies over the past 20 years.

The use of adjunct microbubbles with ultrasound enhances the effectiveness of treatments like thrombolysis and drug delivery, indicating that ultrasound could play a significant role in managing conditions related to thrombosis and inflammation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic ultrasound in cardiology. Nesser, HJ., Karia, DH., Tkalec, W., et al.[2019]

References

1. Germany pubmed.ncbi.nlm.nih.gov

Sonodynamic Therapy Inhibits Fibrogenesis in Rat Cardiac Fibroblasts Induced by TGF-β1. [2019]

2. England pubmed.ncbi.nlm.nih.gov

Therapeutic ultrasound in soft tissue lesions. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Ultrasound enhancement of thrombolytic therapy: observations and mechanisms. [2019]

4. United States pubmed.ncbi.nlm.nih.gov

Analysis of coronary ultrasound thrombolysis endpoints in acute myocardial infarction (ACUTE trial). Results of the feasibility phase. [2019]

5. Germany pubmed.ncbi.nlm.nih.gov

[Therapeutic ultrasound of acute cerebral artery occlusion]. [2021]

6. England pubmed.ncbi.nlm.nih.gov

Therapeutic Ultrasound in Cardiovascular Medicine. [2020]

7. Poland pubmed.ncbi.nlm.nih.gov

[The influence of ultrasound therapy on patient's blood pressure subjected to activity ultrasound]. [2009]

8. England pubmed.ncbi.nlm.nih.gov

Emerging non-cancer applications of therapeutic ultrasound. [2018]

9. Germany pubmed.ncbi.nlm.nih.gov

Therapeutic ultrasound in cardiology. [2019]