Ultrasound Therapy In Cardiac Amyloidosis

NCT ID: NCT04667494

Last Updated: 2025-11-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 70 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-31
• Study Completion Date: 2027-04-30

Brief Summary

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.

Detailed Description

70 subjects will be enrolled in this study in 3 study groups: A) 30 subjects with light chain cardiac amyloidosis B) 30 subjects with transthyretin cardiac amyloidosis and C) 10 subjects without amyloidosis. All subjects will undergo rest 2D echocardiography, rest N-13 ammonia or rubidium-82 perfusion PET, Definity infusion with high mechanical index (MI) imaging defined as sonotherapy in this study protocol.

Conditions

Amyloidosis Cardiac

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Sonotherapy

All participants will undergo sonotherapy

Group Type: EXPERIMENTAL

Sonotherapy

Intervention Type: COMBINATION_PRODUCT

Use of high mechanical index ultrasound therapy with intravenous Definity contrast infusion

Interventions

Sonotherapy

Use of high mechanical index ultrasound therapy with intravenous Definity contrast infusion

Intervention Type: COMBINATION_PRODUCT

Eligibility Criteria

Inclusion Criteria

• Age > 18 years for AL-CA, > 65 years for ATTR-CA, > 65 years for controls
• Willing and able to provide consent
• Diagnosis of systemic light chain amyloidosis by standard criteria (see below) and in hematological remission (normal serum free light chain levels)

• (immunofixation of serum and urine, IgG free light chain (FLC) assay, a biopsy of fat pad/ bone marrow, or organ biopsy, followed by typing of the light chain using immunohistochemistry or immunogold assay with confirmation by Mass spectroscopy as needed) AND
• proof of cardiac involvement by AL amyloidosis
• abnormal cardiac biomarkers (Abnormal high sensitivity TnT 5th generation levels (>9 ng/L: female, >14 ng/L: male) or abnormal age appropriate N terminal pro-brain natriuretic peptide, NT-proBNP (abnormal values: <50 years: >450 pg/ml; 50-75 years:>900 pg/ml; >75 years: >1800 pg/ml) or
• abnormal echocardiogram (wall thickness > 12 mm) or
• abnormal cardiac MRI (wall thickness > 12 mm or extracellular volume > 0.35) OR
• Diagnosis of transthyretin cardiac amyloidosis by standard criteria

• endomyocardial biopsy followed by typing of the transthyretin amyloidosis using immunohistochemistry or immunogold assay with confirmation by Mass spectroscopy as needed
• extracardiac biopsy with typical cardiac imaging findings, or
• grade 2 or grade 3 myocardial uptake of technetium-99m pyrophosphate (PYP) if AL amyloidosis is excluded

Exclusion Criteria

• Hemodynamic instability
• Severe claustrophobia despite use of sedatives
• Decompensated heart failure (unable to lie flat for 1 hour)
• Concomitant non-ischemic non-amyloid heart disease (valvular heart disease or dilated cardiomyopathy)
• Severe valve stenosis or regurgitation in the aortic, mitral or tricuspid valves, including prior valve replacement
• Severe pulmonary artery hypertension
• Severe lung disease
• Known obstructive epicardial coronary artery disease with stenosis > 50% in any single territory
• Prior cardiac surgery
• Regional wall motion abnormality on echocardiogram
• Left ventricular ejection fraction < 40%
• Pregnant state
• Documented allergy to N-13 ammonia or Definity
• Contraindications to DEFINITY® (Perflutren Lipid Microsphere) Injectable Suspension:

o Patients with known or suspected Right-to-left, bi-directional, or transient right-to-left cardiac shunts, Hypersensitivity to perflutren

• Contraindications or challenges to sonotherapy

• Severe electrolyte abnormalities
• QTc prolongation (values are greater than 450 milliseconds in males and greater than 470 milliseconds in females)
• BMI > 35 kg/m2
• Documented intracardiac thrombus
• Atrial fibrillation not on anticoagulation
• Prior history of stroke
• Any other reason determined by the investigator that makes a subject a poor candidate for ultrasound therapy

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: lead

Responsible Party

Sharmila Dorbala

Director, Nuclear Cardiology

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Sharmila Dorbala, MD

Role: PRINCIPAL_INVESTIGATOR

Brigham and Women's Hospital

Locations

Brigham and Women's Hospital

Boston, Massachusetts, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Sharmila Dorbala, MD

Role: CONTACT

Phone: 617-732-6290

Email: sdorbala@bwh.harvard.edu

Facility Contacts

Sharmila Dorbala, MBBS, MPH

Role: primary

Other Identifiers

2020P003179

Identifier Type: -

Identifier Source: org_study_id