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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests ultrasound therapy as a new treatment for cardiac amyloidosis, a condition where abnormal protein buildup affects the heart. The researchers aim to determine if this therapy improves blood flow and heart function. Participants will receive the ultrasound treatment, and the results will be compared before and after the sessions. Suitable candidates have been diagnosed with cardiac amyloidosis and are in remission (their disease is not actively worsening). This study is not suitable for those with severe heart or lung conditions or those unable to lie flat for an hour. As a Phase 4 trial, this research focuses on understanding how this already FDA-approved and effective treatment can benefit more patients.

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 is the safety track record for sonotherapy?

Research has shown that ultrasound therapy, similar to the one tested in this trial, improves blood flow and helps break down blood clots. This suggests the therapy might benefit the heart and be well-tolerated by the body. Since this trial is in a later stage, earlier evidence indicates its safety. Treatments in later trial stages have typically undergone more testing in people, providing more information about possible side effects. However, discussing any concerns with the trial team is crucial to understand personal implications. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about sonotherapy for cardiac amyloidosis because it offers a non-invasive approach that differs significantly from standard treatments like chemotherapy or targeted drug therapies. Sonotherapy uses ultrasound waves to potentially disrupt and break down amyloid deposits in the heart, which is a novel mechanism compared to current methods that primarily focus on managing symptoms or slowing disease progression. This technique could lead to more rapid and targeted treatment with fewer side effects, making it a promising option for patients with this challenging condition.

What evidence suggests that sonotherapy might be an effective treatment for cardiac amyloidosis?

Studies have shown that sonotherapy, a type of ultrasound treatment, can help people with cardiac amyloidosis. One study found that among 29 patients who received ultrasound sessions, moderate levels of ultrasound energy produced the best results. This treatment improves heart function, enhances blood flow, and helps the heart muscle move better. The positive outcomes from these sessions suggest that sonotherapy could be a promising option for managing cardiac amyloidosis. In this trial, all participants will undergo sonotherapy to further evaluate its effectiveness. ^{1 2 4 6 7}

Who Is on the Research Team?

Sharmila Dorbala, MBBS, MPH

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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 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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. withpower.com withpower.com/trial/phase-4-amyloidosis-9-2021-478f0

Ultrasound Therapy for Cardiac Amyloidosis (UTICA Trial) 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 ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT04667494?tab=history&a=7

Record History | ver. 7: 2022-07-18 | NCT04667494 This is a prospective pilot clinical study of subjects with cardiac amyloidosis and control subjects without amyloidosis where we plan to evaluate changes in ...

3. centerwatch.com centerwatch.com/clinical-trials/listings/NCT04667494/ultrasound-therapy-in-cardiac-amyloidosis

Ultrasound Therapy In Cardiac Amyloidosis Study Summary. This is a prospective pilot clinical study of subjects with cardiac amyloidosis and control subjects without amyloidosis where ...

4. ultromics.com ultromics.com/press-releases/ultromics-study-shows-ai-could-improve-early-detection-of-cardiac-amyloidosis

Ultromics Study Shows AI Could Improve Early Detection of ... The AI was able to detect cardiac amyloidosis earlier and more accurately than traditional methods, finding patients who would otherwise have ...

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11333534/

Current Therapies and Future Horizons in Cardiac ... Heart transplantation for ATTR-amyloidosis was first reported in 2003, with combined liver transplantation and good outcome (n=3, 1-year ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12411953/

Outcomes in patients with cardiac amyloidosis undergoing ... LVA was seen in 73% of patients undergoing LA arrhythmia, and it occupied 50.4% of the LA surface, most commonly the posterior wall (53%). However, its presence ...

7. academic.oup.com academic.oup.com/eurheartj/article/46/40/4090/8193027

Cardiac amyloidosis detection from a single ... Sensitivity of the AI model [80.0% (70.3%, 89.8%)] was significantly lower than the TCAS [93.3% (86.4%, 98.3%) P = .02] and significantly higher ...