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Substudy (NCT04456582): Noninvasive Assessment of Myocardial Stiffness by 2D-SWE Ultrasound Technique (Two-dimensional Shear Wave Elastography) in Patients With Amyloidosis and Fabry Disease. (FABRY)

Primary Purpose

Fabry Disease, Amyloidosis

Status

Unknown status

Phase

Not Applicable

Locations

Brazil

Study Type

Interventional

Intervention

Shear-wave elastography

About this trial

This is an interventional diagnostic trial for Fabry Disease focused on measuring Fabry disease, Amyloidosis, Shear-wave elastography

Eligibility Criteria

18 Years - 85 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

- Documented diagnosis of ATTRh with and without cardiac involvement.

For the definition of cardiac involvement by ATTRh, all the criteria below must be presented:

Pathogenic mutation of TTR consistent with ATTRh.
Evidence of cardiac commitment by echocardiography or nuclear magnetic resonance with measurement of the interventricular septum at the end of diastole (SIVd)> 12mm or / and medical history of heart failure, and / or levels of troponin and / or BNP above the reference value without another more likely cause.
Amyloid deposit in cardiac or extra-cardiac tissue (eg, abdominal fat aspirate, salivary gland, connective sheath of the median nerve) confirmed by congo red staining or presence of grade 2 or 3 myocardial scintigraphy (DPD-CT) of cardiac uptake, in cases where the presence of monoclonal gammopathy of undetermined significance (MGUS) was ruled out.
In the presence of MGUS, confirmation of the TTR protein in the tissue is necessary through immunohistochemistry (IHC) or mass spectrometry.

Exclusion Criteria:

Presence of another type of cardiomyopathy such as hypertension, valve or ischemic heart disease (eg, previous myocardial infarction documented with myocardial necrosis markers and electrocardiographic changes).
Presence of diseases other than cardiac amyloidosis, impairing the assessment of functional capacity, such as chronic obstructive pulmonary disease, severe arthritis or peripheral arterial disease, recent or planned orthopedic procedure during the course of the study (eg, spine surgery or under lower limbs) that impairs walking in the 6-minute test evaluation.
Acute coronary heart disease or unstable angina in the past 3 months Report of disease of the sinus or atrioventricular node with indication of a pacemaker, but with no intention of implantation.
Presence of untreated hypothyroidism or hyperthyroidism.
Previous heart, liver or other organ transplant.
Presence of neoplasia in the last 3 years, except for basal and squamous cell carcinomas of skin or cervical cancer in situ previously treated.
Presence of other medical conditions or comorbidities that, in the investigator's opinion, could interfere with the course of the study or the interpretation of the data.
Pregnancy.
History of alcohol abuse in the last 2 years or excessive daily alcohol intake (for women, more than 14 units per week; for men, more than 21 units of alcohol per week [unit: one glass of wine (125ml) = one dose of distillate = 332.5ml of beer).

Sites / Locations

Instituto do Coração - Hospital das Clínicas da Faculdade de Medicina da Universidade de São PauloRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Active Comparator

Placebo Comparator

Arm Label

Fabry disease patients

Amyloidosis transthyretin with cardiac commitment

Healthy subjects

Arm Description

Patients diagnosed with Fabry disease. Interventions will be as follows: Shear wave myocardial elastography to assess myocardial stiffness by non-invasively quantifying diastolic myocardial elasticity (EMD) in Fabry disease (DF) and cardiac amyloidosis (AC) in the ATTRh form and correlating with other complementary imaging tests and laboratory tests (electrocardiogram, 2D echocardiogram, troponin and BNP) and with a 6-minute walk test and quality of life questionnaires.

Patients diagnosed with amyloidosis who present cardiac commitment. Interventions will be as follows: Shear wave myocardial elastography to assess myocardial stiffness by non-invasively quantifying diastolic myocardial elasticity (EMD) in Fabry disease (DF) and cardiac amyloidosis (AC) in the ATTRh form and correlating with other complementary imaging tests and laboratory tests (electrocardiogram, 2D echocardiogram, troponin and BNP) and with a 6-minute walk test and quality of life questionnaires.

Healthy patients. Interventions will be as follows: Shear wave myocardial elastography to assess myocardial stiffness by non-invasively quantifying diastolic myocardial elasticity (EMD) in Fabry disease (DF) and cardiac amyloidosis (AC) in the ATTRh form and correlating with other complementary imaging tests and laboratory tests (electrocardiogram, 2D echocardiogram, troponin and BNP) and with a 6-minute walk test.

Outcomes

Primary Outcome Measures

Myocardial stiffness

To evaluate the diastolic myocardial elasticity in patients with Fabry's disease and compare it with the ATTR group with cardiac involvement and the control group.

Secondary Outcome Measures

Systolic and diastolic function

To correlate diastolic myocardial elasticity with systolic and diastolic function indexes assessed by two-dimensional echocardiogram and with strain analysis using the speckle tracking technique;

Brain Natriuretic Peptide and troponin assessment

To correlate diastolic myocardial elasticity with a 6-minute walk test, Brain Natriuretic Peptide and troponin.

Full Information

NCT ID

NCT04893889

First Posted

May 14, 2021

Last Updated

May 14, 2021

Sponsor

University of Sao Paulo General Hospital

Collaborators

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT04893889

Brief Title

Substudy (NCT04456582): Noninvasive Assessment of Myocardial Stiffness by 2D-SWE Ultrasound Technique (Two-dimensional Shear Wave Elastography) in Patients With Amyloidosis and Fabry Disease.

Acronym

FABRY

Official Title

Substudy (NCT04456582): Noninvasive Assessment of Myocardial Stiffness by 2D-SWE Ultrasound Technique (Two-dimensional Shear Wave Elastography) in Patients With Amyloidosis and Fabry Disease.

Study Type

Interventional

2. Study Status

Record Verification Date

April 2021

Overall Recruitment Status

Unknown status

Study Start Date

September 9, 2020 (Actual)

Primary Completion Date

August 31, 2021 (Anticipated)

Study Completion Date

March 30, 2022 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Sao Paulo General Hospital

Collaborators

Pfizer

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

Introduction: Heart failure with preserved systolic function encompasses several different diseases, but which have diastolic dysfunction and its components in common: myocardial stiffness and altered relaxation. Myocardial stiffness represents an important parameter for diagnosis and prognosis, but only changes in relaxation are evaluated in clinical practice. Cardiac elastography has been proposed as a diagnostic modality for noninvasive assessment of myocardial stiffness. Objective: The aim of our study is to investigate the potential of myocardial elastography by shear waves to assess myocardial stiffness by non-invasively quantifying diastolic myocardial elasticity (EMD) in Fabry disease (DF) and cardiac amyloidosis (AC ) in the ATTRh form and correlate with other complementary imaging and laboratory tests (electrocardiogram, 2D echocardiogram, troponin and BNP) and with a 6-minute walk test and quality of life questionnaires. Material and methods: 60 adults will be prospectively included: 20 patients with Fabry disease, 40 patients with hRTRT (20 with cardiac involvement) and 20 patients as a control group. Echocardiography, electrocardiogram and laboratory evaluations will be performed. The elastocardiographic assessment of myocardial stiffness will be performed in ultrasound equipment (Canon, Aplio i800) using a multifrequency convex transducer, under specific adjustment of the equipment to perform myocardial elastography.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Fabry Disease, Amyloidosis

Keywords

Fabry disease, Amyloidosis, Shear-wave elastography

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

Outcomes Assessor

Allocation

Non-Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Fabry disease patients

Arm Type

Experimental

Arm Description

Arm Title

Amyloidosis transthyretin with cardiac commitment

Arm Type

Active Comparator

Arm Description

Arm Title

Healthy subjects

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Diagnostic Test

Intervention Name(s)

Shear-wave elastography

Intervention Description

Myocardial shear wave elastography to assess myocardial stiffness by non-invasively quantifying diastolic myocardial elasticity.

Primary Outcome Measure Information:

Title

Myocardial stiffness

Description

To evaluate the diastolic myocardial elasticity in patients with Fabry's disease and compare it with the ATTR group with cardiac involvement and the control group.

Time Frame

7 months

Secondary Outcome Measure Information:

Title

Systolic and diastolic function

Description

To correlate diastolic myocardial elasticity with systolic and diastolic function indexes assessed by two-dimensional echocardiogram and with strain analysis using the speckle tracking technique;

Time Frame

7 months

Title

Brain Natriuretic Peptide and troponin assessment

Description

To correlate diastolic myocardial elasticity with a 6-minute walk test, Brain Natriuretic Peptide and troponin.

Time Frame

7 months

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

85 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: - Documented diagnosis of ATTRh with and without cardiac involvement. For the definition of cardiac involvement by ATTRh, all the criteria below must be presented: Pathogenic mutation of TTR consistent with ATTRh. Evidence of cardiac commitment by echocardiography or nuclear magnetic resonance with measurement of the interventricular septum at the end of diastole (SIVd)> 12mm or / and medical history of heart failure, and / or levels of troponin and / or BNP above the reference value without another more likely cause. Amyloid deposit in cardiac or extra-cardiac tissue (eg, abdominal fat aspirate, salivary gland, connective sheath of the median nerve) confirmed by congo red staining or presence of grade 2 or 3 myocardial scintigraphy (DPD-CT) of cardiac uptake, in cases where the presence of monoclonal gammopathy of undetermined significance (MGUS) was ruled out. In the presence of MGUS, confirmation of the TTR protein in the tissue is necessary through immunohistochemistry (IHC) or mass spectrometry. Exclusion Criteria: Presence of another type of cardiomyopathy such as hypertension, valve or ischemic heart disease (eg, previous myocardial infarction documented with myocardial necrosis markers and electrocardiographic changes). Presence of diseases other than cardiac amyloidosis, impairing the assessment of functional capacity, such as chronic obstructive pulmonary disease, severe arthritis or peripheral arterial disease, recent or planned orthopedic procedure during the course of the study (eg, spine surgery or under lower limbs) that impairs walking in the 6-minute test evaluation. Acute coronary heart disease or unstable angina in the past 3 months Report of disease of the sinus or atrioventricular node with indication of a pacemaker, but with no intention of implantation. Presence of untreated hypothyroidism or hyperthyroidism. Previous heart, liver or other organ transplant. Presence of neoplasia in the last 3 years, except for basal and squamous cell carcinomas of skin or cervical cancer in situ previously treated. Presence of other medical conditions or comorbidities that, in the investigator's opinion, could interfere with the course of the study or the interpretation of the data. Pregnancy. History of alcohol abuse in the last 2 years or excessive daily alcohol intake (for women, more than 14 units per week; for men, more than 21 units of alcohol per week [unit: one glass of wine (125ml) = one dose of distillate = 332.5ml of beer).

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Fabio Fernandes, MD, PhD

Phone

+551126615057

fabio.fernandes@incor.usp.br

First Name & Middle Initial & Last Name or Official Title & Degree

Caio R Cafezeiro, MD

Phone

+551126615057

caiocafezeiro@usp.br

Facility Information:

Facility Name

Instituto do Coração - Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo

City

São Paulo

State/Province

Sao Paulo

ZIP/Postal Code

05403-900

Country

Brazil

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Fabio Fernandes, MD, PhD

Phone

+551126615057

fabio.fernandes@incor.usp.br

First Name & Middle Initial & Last Name & Degree

Caio R Cafezeiro, MD

Phone

+551126615057

caiocafezeiro@usp.br

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

Substudy (NCT04456582): Noninvasive Assessment of Myocardial Stiffness by 2D-SWE Ultrasound Technique (Two-dimensional Shear Wave Elastography) in Patients With Amyloidosis and Fabry Disease.

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