Ultrasound Therapy In Cardiac Amyloidosis

study id #: NCT04667494

condition: Amyloidosis Cardiac

status: Recruiting

purpose:

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.

intervention: Sonotherapy

results: https://clinicaltrials.gov/ct2/show/results/NCT04667494

last updated: February 22, 2024

start date: August 31, 2023

estimated completion: June 30, 2025

last updated: December 7, 2023

phase of development: Phase 4

size / enrollment: 70

study 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.

primary outcomes:

• Myocardial Blood Flow
  N-13 ammonia or Rubidium-82 PET based measure of myocardial blood flow in ml/gm/min
• 1 day
  Systolic Function
  Global Longitudinal Strain by echocardiography
• 1 day
  Diastolic Function
  Echo measured mitral e' velocity
• 1 day
  

inclusion 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: 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 CMR

Implantable Cardioverter Defibrillator (ICD)
Significant renal dysfunction with estimated glomerular filtration rate < 30 ml/min/m2.
Dialysis

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

sponsor: Brigham and Women's Hospital

contacts: Sharmila Dorbala, MD, 617-732-6290, [email protected]

investigators: Sharmila Dorbala, MD,Brigham And Women's Hospital

trial center locations:

• United States, Massachusetts
  Brigham and Women’s Hospital
  Sharmila Dorbala, MBBS, MPH, 617-732-6290, [email protected]