Ultrasound Therapy In Cardiac Amyloidosis (UTICA)

Mass General Brigham

Status and phase

Enrolling

Phase 4

Conditions

Amyloidosis Cardiac

Treatments

Combination Product: Sonotherapy

Study type

Interventional

Funder types

Other

Identifiers

NCT04667494

2020P003179

Details and patient eligibility

About

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.

Full 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.

Enrollment

70 estimated patients

Sex

All

Ages

18 to 90 years old

Volunteers

Accepts Healthy Volunteers

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