Ultrasound Therapy In Cardiac Amyloidosis (UTICA)

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.

Study Overview

• Status: Recruiting
• Conditions: Amyloidosis Cardiac
• Intervention / Treatment: Combination product: 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.

• Study Type: Interventional
• Enrollment (Estimated): 70
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Sharmila Dorbala, MD; Phone Number: 617-732-6290; Email: sdorbala@bwh.harvard.edu

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Recruiting
      • Brigham and Women's Hospital
      • Contact: Sharmila Dorbala, MBBS, MPH; Phone Number: 617-732-6290; Email: sdorbala@partners.org
      • Principal Investigator: Sharmila Dorbala, MBBS, MPH

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sonotherapy; All participants will undergo sonotherapy	Combination product: Sonotherapy; Use of high mechanical index ultrasound therapy with intravenous Definity contrast infusion

What is the study measuring?

Primary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Brigham and Women's Hospital
• Investigators: Principal Investigator: Sharmila Dorbala, MD, Brigham and Women's Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 31, 2023
• Primary Completion (Estimated): April 30, 2026
• Study Completion (Estimated): April 30, 2027

Study Registration Dates

• First Submitted: December 3, 2020
• First Submitted That Met QC Criteria: December 8, 2020
• First Posted (Actual): December 14, 2020

Study Record Updates

• Last Update Posted (Estimated): March 6, 2024
• Last Update Submitted That Met QC Criteria: March 5, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis
• Other Study ID Numbers: 2020P003179

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: There is no plan to share IRD

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes