Ultrasound Therapy In Cardiac Amyloidosis (UTICA)
Primary Purpose
Amyloidosis Cardiac
Status
Recruiting
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Sonotherapy
Sponsored by
About this trial
This is an interventional treatment trial for Amyloidosis Cardiac
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 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
Sites / Locations
- Brigham and Women's HospitalRecruiting
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Sonotherapy
Arm Description
All participants will undergo sonotherapy
Outcomes
Primary Outcome Measures
Myocardial Blood Flow
N-13 ammonia PET based measure of myocardial blood flow in ml/gm/min
Systolic Function
Global Longitudinal Strain by echocardiography
Diastolic Function
Echo measured mitral e' velocity
Secondary Outcome Measures
Full Information
NCT ID
NCT04667494
First Posted
December 3, 2020
Last Updated
July 25, 2023
Sponsor
Brigham and Women's Hospital
1. Study Identification
Unique Protocol Identification Number
NCT04667494
Brief Title
Ultrasound Therapy In Cardiac Amyloidosis
Acronym
UTICA
Official Title
Ultrasound Therapy In Cardiac Amyloidosis
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 15, 2023 (Actual)
Primary Completion Date
June 30, 2025 (Anticipated)
Study Completion Date
June 30, 2025 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Brigham and Women's Hospital
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Device Product Not Approved or Cleared by U.S. FDA
Yes
Data Monitoring Committee
No
5. Study Description
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 perfusion PET, Definity infusion with high mechanical index (MI) imaging defined as sonotherapy in this study protocol.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Amyloidosis Cardiac
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
Outcome measures will be evaluated before and after intervention with sonotherapy.
Masking
None (Open Label)
Allocation
N/A
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Sonotherapy
Arm Type
Experimental
Arm Description
All participants will undergo sonotherapy
Intervention Type
Combination Product
Intervention Name(s)
Sonotherapy
Intervention Description
Use of high mechanical index ultrasound therapy with intravenous Definity contrast infusion
Primary Outcome Measure Information:
Title
Myocardial Blood Flow
Description
N-13 ammonia PET based measure of myocardial blood flow in ml/gm/min
Time Frame
1 day
Title
Systolic Function
Description
Global Longitudinal Strain by echocardiography
Time Frame
1 day
Title
Diastolic Function
Description
Echo measured mitral e' velocity
Time Frame
1 day
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Sharmila Dorbala, MD
Phone
617-732-6290
Email
sdorbala@bwh.harvard.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Sharmila Dorbala, MD
Organizational Affiliation
Brigham and Women's Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Brigham and Women's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sharmila Dorbala, MBBS, MPH
Phone
617-732-6290
Email
sdorbala@partners.org
First Name & Middle Initial & Last Name & Degree
Sharmila Dorbala, MBBS, MPH
12. IPD Sharing Statement
Plan to Share IPD
No
IPD Sharing Plan Description
There is no plan to share IRD
Learn more about this trial
Ultrasound Therapy In Cardiac Amyloidosis
We'll reach out to this number within 24 hrs