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Noninvasive Assessment of Myocardial Stiffness by 2D-SWE Ultrasound Technique (Bidimensional Shear Wave Elastography) in Patients With Transthyretin Amyloidosis (ELAST-2D)

Primary Purpose

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 Amyloidosis focused on measuring Amyloidosis, Elastography, Cardiac, Miocardical stiffness

Eligibility Criteria

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

Inclusion Criteria:

Documented diagnosis of HRTR 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

University of Sao Paulo Medical School - The Heart InstituteRecruiting

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Placebo Comparator

Arm Label

Amyloidosis transthyretin with cardiac commitment

Amyloidosis transthyretin without cardiac commitment

Healthy subjects

Arm Description

Shear wave elastography (SWE) will be used to evaluate to assess miocardial elasticity.

Outcomes

Primary Outcome Measures

Dyastolic miocardical elasticity

Diastolic myocardial elasticity could provide a more direct response to the constitution of the tissue and allow a simple, safe and diastolic function assessment and early initiation of specific treatment.

Secondary Outcome Measures

Full Information

NCT ID

NCT04456582

First Posted

June 29, 2020

Last Updated

June 29, 2020

Sponsor

Fábio Fernandes

Collaborators

Pfizer

1. Study Identification

Unique Protocol Identification Number

NCT04456582

Brief Title

Noninvasive Assessment of Myocardial Stiffness by 2D-SWE Ultrasound Technique (Bidimensional Shear Wave Elastography) in Patients With Transthyretin Amyloidosis

Acronym

ELAST-2D

Official Title

Noninvasive Assessment of Myocardial Stiffness by 2D-SWE Ultrasound Technique (Bidimensional Shear Wave Elastography) in Patients With Transthyretin Amyloidosis

Study Type

Interventional

2. Study Status

Record Verification Date

June 2020

Overall Recruitment Status

Unknown status

Study Start Date

June 3, 2020 (Actual)

Primary Completion Date

January 31, 2021 (Anticipated)

Study Completion Date

May 29, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Fábio Fernandes

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

Amyloidosis by mutation of the transthyretin gene (ATTRh) is part of a group of diseases in which the deposit of structurally abnormal proteins (amyloid fibrils) affects multiple organs such as: liver, kidney, eyes, nervous system, gastrointestinal tract and heart, and, finally, it increases the morbidity and mortality of affected patients. This deposit in the myocardium is manifested syndromically as heart failure with preserved or slightly reduced systolic function, and important diastolic dysfunction. The analysis of diastolic function comprises two components: the assessment of active relaxation, dependent on preload and afterload, and the assessment of the passive properties of the tissue - its hardness or rigidity. Myocardial stiffness represents an important parameter for diagnosis and prognosis, but its evaluation is not included in conventional echocardiography. Cardiac elastography has recently been proposed as a non-invasive diagnostic modality to assess myocardial stiffness.

6. Conditions and Keywords

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

Amyloidosis

Keywords

Amyloidosis, Elastography, Cardiac, Miocardical stiffness

7. Study Design

Primary Purpose

Diagnostic

Study Phase

Not Applicable

Interventional Study Model

Parallel Assignment

Masking

None (Open Label)

Allocation

Non-Randomized

Enrollment

60 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Amyloidosis transthyretin with cardiac commitment

Arm Type

Experimental

Arm Description

Shear wave elastography (SWE) will be used to evaluate to assess miocardial elasticity.

Arm Title

Amyloidosis transthyretin without cardiac commitment

Arm Type

Experimental

Arm Description

Shear wave elastography (SWE) will be used to evaluate to assess miocardial elasticity.

Arm Title

Healthy subjects

Arm Type

Placebo Comparator

Arm Description

Shear wave elastography (SWE) will be used to evaluate to assess miocardial elasticity.

Intervention Type

Procedure

Intervention Name(s)

Shear wave elastography

Intervention Description

The elastographic technique by ultrasound (USE), shear waves or shear wave elastography (SWE), quantitatively evaluates tissue stiffness by mapping the propagation of acoustic waves (shear waves), in a non-invasive manner and without emission of ionizing radiation. Their speeds are tracked by the ultrasound equipment after tissue deformation occurs, generated by pulses of acoustic radiation (ARFI) of the transducer itself. Assuming the correlation between tissue stiffness and increased acoustic propagation speeds, it is possible to describe mathematically the elasticity of tissues by measuring specific acoustic waves.

Primary Outcome Measure Information:

Title

Dyastolic miocardical elasticity

Description

Time Frame

Around 6 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 HRTR 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).

Facility Information:

Facility Name

University of Sao Paulo Medical School - The Heart Institute

City

Sao Paulo

ZIP/Postal Code

05403-000

Country

Brazil

Individual Site Status

Recruiting

Facility Contact: