ATTR Amyloid Cardiomyopathy: Characterization of Extracellular Vesicles as Potential Disease Stratifiers and Prognostic Biomarkers (EV-ATTR)

December 16, 2025 updated by: FELIX JOSÉ ALVAREZ RAMIRES, University of Sao Paulo General Hospital

This study explores whether extracellular vesicles (EVs) tiny particles released into the bloodstream by cells can serve as early and minimally invasive biomarkers for transthyretin amyloid cardiomyopathy (ATTR-CM). Because ATTR-CM is often diagnosed only after significant heart damage has occurred, there is an urgent need for earlier detection methods.

The study will enroll individuals with different clinical presentations of transthyretin amyloidosis, along with healthy controls. Participants will undergo blood sampling, cardiac imaging (including echocardiography, cardiac MRI, and scintigraphy when indicated), and molecular EV analysis.

By comparing EV profiles across groups, the study aims to determine whether these vesicles reflect early cardiac involvement, track disease progression, and support more accurate and timely diagnosis. Ultimately, this research seeks to improve clinical decision-making and patient outcomes in ATTR cardiomyopathy.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Transthyretin amyloid cardiomyopathy (ATTR-CM) is a progressive infiltrative disease caused by the deposition of misfolded transthyretin protein in the myocardium. Despite advances in imaging and treatment, early detection and accurate risk stratification remain major challenges, often resulting in delayed diagnosis and worse clinical outcomes.

This prospective observational study will enroll 70 adult participants, distributed into four predefined groups:

  • ATTR-CM with myocardial dysfunction (n = 20)
  • Hereditary ATTR with predominant neurologic involvement (n = 20)
  • Genotype-positive individuals without clinical manifestation (n = 10)
  • Healthy controls (n = 20)

All participants will undergo blood collection for extracellular vesicle (EV) isolation and molecular profiling. EVs are nanoscale particles released by cells that carry proteins, lipids, and nucleic acids reflective of their cellular origin and physiological state, potentially serving as minimally invasive biomarkers.

Participants with cardiac involvement will additionally undergo standardized cardiac evaluations, including echocardiography, cardiac MRI, and nuclear imaging when indicated. Clinical data, functional status, and laboratory parameters will be correlated with EV characteristics to assess their association with disease severity and progression.

By integrating EV profiling with clinical and imaging findings across different phenotypes and disease stages, this study aims to identify biomarkers capable of improving diagnostic accuracy, tracking disease evolution, and supporting personalized care strategies in ATTR amyloidosis.

Study Type

Observational

Enrollment (Estimated)

70

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Brazil
    • São Paulo
      • São Paulo, São Paulo, Brazil, 05403000
        • Recruiting
        • Instituto do Coracao, HCFMUSP
        • Sub-Investigator:
          • Fabio Fernandes, MD, PhD
        • Contact:
        • Contact:
          • Camila R Moreno, PhD
          • Phone Number: 5511994849265
        • Principal Investigator:
          • Felix JA Ramires, MD, PhD
        • Sub-Investigator:
          • Camila R Moreno, PhD
        • Sub-Investigator:
          • Keila CB Fonseca, PhD
        • Sub-Investigator:
          • Orlando Ribeiro, BSc
        • Sub-Investigator:
          • Allecineia B Cruz, PhD
        • Sub-Investigator:
          • Bruno V Kerges, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

This study will enroll adult participants aged 18 years or older, including patients with confirmed transthyretin cardiac amyloidosis (with or without myocardial dysfunction), as well as healthy volunteers without known cardiac disease. The population includes individuals with different clinical presentations of ATTR and matched controls for comparative analysis.

Description

Inclusion Criteria:

  • Adult patients aged 18 years or older;
  • Confirmed diagnosis of transthyretin cardiac amyloidosis (TTR-CA), with or without myocardial dysfunction, according to established diagnostic criteria;
  • Willingness to comply with study procedures and requirements;
  • Ability to provide written informed consent.

Exclusion Criteria:

  • Presence of other significant cardiac conditions that may interfere with study outcomes, such as severe coronary artery disease or major valvular disease;
  • Inability to provide informed consent or to participate in the required clinical assessments and examinations.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
TTR-CA + DM
TTR amyloid cardiomyopathy and myocardial dysfunction
TTR-A
TTR amyloidosis and neurological involvement
TTR-Gen
TTR amyloid genotype without phenotypic expression
CTL
healthy controls

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Serum concentration of circulating extracellular vesicles (EVs)
Time Frame: baseline
Quantification of the total concentration of circulating extracellular vesicles isolated from peripheral blood, expressed as number of particles per mL, measured by Nanoparticle Tracking Analysis (NTA - NanoSight), in participants with different clinical presentations of transthyretin amyloidosis (ATTR) and in healthy controls.
baseline
Circulating extracellular vesicle protein profile
Time Frame: baseline
Protein profiling of circulating extracellular vesicles isolated from peripheral blood, including protein identification and assessment of relative abundance by mass spectrometry, followed by targeted validation and quantification of selected proteins using Western blotting and/or ELISA. Results will be reported as relative protein expression intensity or, when applicable, as absolute concentration (ng/mL), in participants with transthyretin amyloidosis (ATTR) and healthy controls, assessed at baseline.
baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Correlation between circulating extracellular vesicle concentration and echocardiographic parameters
Time Frame: baseline
Correlation between plasma concentration of circulating extracellular vesicles, measured as particles/mL by Nanoparticle Tracking Analysis, and cardiac structure and function parameters assessed by transthoracic echocardiography, including interventricular septal thickness (mm), left ventricular ejection fraction (%), and global longitudinal strain (%), analyzed using Pearson or Spearman correlation coefficients as appropriate, in participants with transthyretin amyloidosis (ATTR) and healthy controls.
baseline
Correlation between extracellular vesicle molecular profile and cardiac magnetic resonance findings
Time Frame: baseline
Correlation between the molecular profile of circulating extracellular vesicles, including protein levels assessed by Western blotting and/or ELISA and microRNA expression assessed by RT-qPCR, and cardiac involvement parameters evaluated by cardiac magnetic resonance imaging, including extracellular volume fraction (ECV, %) and presence or absence of late gadolinium enhancement, analyzed using correlation methods as appropriate, in participants with transthyretin amyloidosis (ATTR) and healthy controls.
baseline
Correlation between extracellular vesicle characteristics and myocardial uptake on scintigraphy
Time Frame: baseline
Correlation between circulating extracellular vesicle concentration, measured as particles/mL by Nanoparticle Tracking Analysis, and extracellular vesicle molecular characteristics assessed by RT-qPCR and Western blotting, and the degree of myocardial uptake evaluated by bone scintigraphy using an appropriate radiotracer and visual scoring system (e.g., Perugini grade 0-3), analyzed using correlation methods as appropriate, in participants with transthyretin amyloidosis (ATTR) and healthy controls.
baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Sao Paulo General Hospital

Collaborators

InCor Heart Institute

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 18, 2024

Primary Completion (Estimated)

May 31, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted

November 25, 2025

First Submitted That Met QC Criteria

December 16, 2025

First Posted (Estimated)

January 2, 2026

Study Record Updates

Last Update Posted (Estimated)

January 2, 2026

Last Update Submitted That Met QC Criteria

December 16, 2025

Last Verified

December 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 83160124.2.0000.0068

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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