ATTR Amyloid Cardiomyopathy: Characterization of Extracellular Vesicles as Potential Disease Stratifiers and Prognostic Biomarkers

NCT07314268 | Recruiting DMC

• 1 other identifier: 83160124.2.0000.0068
• Study Type: observational
• Target: 70
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Amyloidosis Cardiac; Amyloidosis, Hereditary; Amyloidosis Transthyretin; Wild-type ATTR Amyloidosis

Keywords

Early Diagnosis; Serum Biomarkers; Transthyretin Amyloid Cardiomyopathy; ATTR; Vesicle Protein Signature

Outcome Measures

Primary Outcomes (2)

• Serum concentration of circulating extracellular vesicles (EVs)

  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

  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 Outcomes (3)

• Correlation between circulating extracellular vesicle concentration and echocardiographic parameters

  baseline

• Correlation between extracellular vesicle molecular profile and cardiac magnetic resonance findings

  baseline

• Correlation between extracellular vesicle characteristics and myocardial uptake on scintigraphy

  baseline

Study Arms (4)

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• 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.

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• InCor Heart Institute: collaborator
• University of Sao Paulo General Hospital: lead

Study Sites (1)

Instituto do Coracao, HCFMUSP

São Paulo, São Paulo, 05403000, Brazil

RECRUITING

Related Publications (23)

• Perez-Gonzalez R, Kim Y, Miller C, Pacheco-Quinto J, Eckman EA, Levy E. Extracellular vesicles: where the amyloid precursor protein carboxyl-terminal fragments accumulate and amyloid-beta oligomerizes. FASEB J. 2020 Sep;34(9):12922-12931. doi: 10.1096/fj.202000823R. Epub 2020 Aug 9.

  PMID: 32772431 BACKGROUND

• Moreno CR, Ramires JAF, Lotufo PA, Soeiro AM, Oliveira LMDS, Ikegami RN, Kawakami JT, Pereira JJ, Reis MM, Higuchi ML. Morphomolecular Characterization of Serum Nanovesicles From Microbiomes Differentiates Stable and Infarcted Atherosclerotic Patients. Front Cardiovasc Med. 2021 Aug 5;8:694851. doi: 10.3389/fcvm.2021.694851. eCollection 2021.

  PMID: 34422924 BACKGROUND

• Roura S, Gamez-Valero A, Lupon J, Galvez-Monton C, Borras FE, Bayes-Genis A. Proteomic signature of circulating extracellular vesicles in dilated cardiomyopathy. Lab Invest. 2018 Oct;98(10):1291-1299. doi: 10.1038/s41374-018-0044-5. Epub 2018 Mar 14.

  PMID: 29540862 BACKGROUND

• Bakhshandeh B, Kamaleddin MA, Aalishah K. A Comprehensive Review on Exosomes and Microvesicles as Epigenetic Factors. Curr Stem Cell Res Ther. 2017;12(1):31-36. doi: 10.2174/1574888x11666160709211528.

  PMID: 27396390 BACKGROUND

• van der Pol E, Hoekstra AG, Sturk A, Otto C, van Leeuwen TG, Nieuwland R. Optical and non-optical methods for detection and characterization of microparticles and exosomes. J Thromb Haemost. 2010 Dec;8(12):2596-607. doi: 10.1111/j.1538-7836.2010.04074.x.

  PMID: 20880256 BACKGROUND

• Ridger VC, Boulanger CM, Angelillo-Scherrer A, Badimon L, Blanc-Brude O, Bochaton-Piallat ML, Boilard E, Buzas EI, Caporali A, Dignat-George F, Evans PC, Lacroix R, Lutgens E, Ketelhuth DFJ, Nieuwland R, Toti F, Tunon J, Weber C, Hoefer IE. Microvesicles in vascular homeostasis and diseases. Position Paper of the European Society of Cardiology (ESC) Working Group on Atherosclerosis and Vascular Biology. Thromb Haemost. 2017 Jun 28;117(7):1296-1316. doi: 10.1160/TH16-12-0943. Epub 2017 Jun 1.

  PMID: 28569921 BACKGROUND

• Sunkara V, Woo HK, Cho YK. Emerging techniques in the isolation and characterization of extracellular vesicles and their roles in cancer diagnostics and prognostics. Analyst. 2016 Jan 21;141(2):371-81. doi: 10.1039/c5an01775k.

  PMID: 26535415 BACKGROUND

• Roy S, Hochberg FH, Jones PS. Extracellular vesicles: the growth as diagnostics and therapeutics; a survey. J Extracell Vesicles. 2018 Feb 26;7(1):1438720. doi: 10.1080/20013078.2018.1438720. eCollection 2018.

  PMID: 29511461 BACKGROUND

• Stremersch S, De Smedt SC, Raemdonck K. Therapeutic and diagnostic applications of extracellular vesicles. J Control Release. 2016 Dec 28;244(Pt B):167-183. doi: 10.1016/j.jconrel.2016.07.054. Epub 2016 Aug 2.

  PMID: 27491882 BACKGROUND

• Gillmore JD, Maurer MS, Falk RH, Merlini G, Damy T, Dispenzieri A, Wechalekar AD, Berk JL, Quarta CC, Grogan M, Lachmann HJ, Bokhari S, Castano A, Dorbala S, Johnson GB, Glaudemans AW, Rezk T, Fontana M, Palladini G, Milani P, Guidalotti PL, Flatman K, Lane T, Vonberg FW, Whelan CJ, Moon JC, Ruberg FL, Miller EJ, Hutt DF, Hazenberg BP, Rapezzi C, Hawkins PN. Nonbiopsy Diagnosis of Cardiac Transthyretin Amyloidosis. Circulation. 2016 Jun 14;133(24):2404-12. doi: 10.1161/CIRCULATIONAHA.116.021612. Epub 2016 Apr 22.

  PMID: 27143678 BACKGROUND

• Fontana M, Pica S, Reant P, Abdel-Gadir A, Treibel TA, Banypersad SM, Maestrini V, Barcella W, Rosmini S, Bulluck H, Sayed RH, Patel K, Mamhood S, Bucciarelli-Ducci C, Whelan CJ, Herrey AS, Lachmann HJ, Wechalekar AD, Manisty CH, Schelbert EB, Kellman P, Gillmore JD, Hawkins PN, Moon JC. Prognostic Value of Late Gadolinium Enhancement Cardiovascular Magnetic Resonance in Cardiac Amyloidosis. Circulation. 2015 Oct 20;132(16):1570-9. doi: 10.1161/CIRCULATIONAHA.115.016567. Epub 2015 Sep 11.

  PMID: 26362631 BACKGROUND

• Maurer MS, Elliott P, Comenzo R, Semigran M, Rapezzi C. Addressing Common Questions Encountered in the Diagnosis and Management of Cardiac Amyloidosis. Circulation. 2017 Apr 4;135(14):1357-1377. doi: 10.1161/CIRCULATIONAHA.116.024438.

  PMID: 28373528 BACKGROUND

• Gonzalez-Lopez E, Gagliardi C, Dominguez F, Quarta CC, de Haro-Del Moral FJ, Milandri A, Salas C, Cinelli M, Cobo-Marcos M, Lorenzini M, Lara-Pezzi E, Foffi S, Alonso-Pulpon L, Rapezzi C, Garcia-Pavia P. Clinical characteristics of wild-type transthyretin cardiac amyloidosis: disproving myths. Eur Heart J. 2017 Jun 21;38(24):1895-1904. doi: 10.1093/eurheartj/ehx043.

  PMID: 28329248 BACKGROUND

• Treibel TA, Fontana M, Gilbertson JA, Castelletti S, White SK, Scully PR, Roberts N, Hutt DF, Rowczenio DM, Whelan CJ, Ashworth MA, Gillmore JD, Hawkins PN, Moon JC. Occult Transthyretin Cardiac Amyloid in Severe Calcific Aortic Stenosis: Prevalence and Prognosis in Patients Undergoing Surgical Aortic Valve Replacement. Circ Cardiovasc Imaging. 2016 Aug;9(8):e005066. doi: 10.1161/CIRCIMAGING.116.005066.

  PMID: 27511979 BACKGROUND

• Galat A, Guellich A, Bodez D, Slama M, Dijos M, Zeitoun DM, Milleron O, Attias D, Dubois-Rande JL, Mohty D, Audureau E, Teiger E, Rosso J, Monin JL, Damy T. Aortic stenosis and transthyretin cardiac amyloidosis: the chicken or the egg? Eur Heart J. 2016 Dec 14;37(47):3525-3531. doi: 10.1093/eurheartj/ehw033. Epub 2016 Feb 22.

  PMID: 26908951 BACKGROUND

• Ruberg FL, Berk JL. Transthyretin (TTR) cardiac amyloidosis. Circulation. 2012 Sep 4;126(10):1286-300. doi: 10.1161/CIRCULATIONAHA.111.078915. No abstract available.

  PMID: 22949539 BACKGROUND

• Mankad AK, Shah KB. Transthyretin Cardiac Amyloidosis. Curr Cardiol Rep. 2017 Aug 24;19(10):97. doi: 10.1007/s11886-017-0911-5.

  PMID: 28840452 BACKGROUND

• Damy T, Costes B, Hagege AA, Donal E, Eicher JC, Slama M, Guellich A, Rappeneau S, Gueffet JP, Logeart D, Plante-Bordeneuve V, Bouvaist H, Huttin O, Mulak G, Dubois-Rande JL, Goossens M, Canoui-Poitrine F, Buxbaum JN. Prevalence and clinical phenotype of hereditary transthyretin amyloid cardiomyopathy in patients with increased left ventricular wall thickness. Eur Heart J. 2016 Jun 14;37(23):1826-34. doi: 10.1093/eurheartj/ehv583. Epub 2015 Nov 3.

  PMID: 26537620 BACKGROUND

• Maleszewski JJ. Cardiac amyloidosis: pathology, nomenclature, and typing. Cardiovasc Pathol. 2015 Nov-Dec;24(6):343-50. doi: 10.1016/j.carpath.2015.07.008. Epub 2015 Aug 1.

  PMID: 26361138 BACKGROUND

• Banypersad SM, Moon JC, Whelan C, Hawkins PN, Wechalekar AD. Updates in cardiac amyloidosis: a review. J Am Heart Assoc. 2012 Apr;1(2):e000364. doi: 10.1161/JAHA.111.000364. Epub 2012 Apr 24. No abstract available.

  PMID: 23130126 BACKGROUND

• Alexander KM, Orav J, Singh A, Jacob SA, Menon A, Padera RF, Kijewski MF, Liao R, Di Carli MF, Laubach JP, Falk RH, Dorbala S. Geographic Disparities in Reported US Amyloidosis Mortality From 1979 to 2015: Potential Underdetection of Cardiac Amyloidosis. JAMA Cardiol. 2018 Sep 1;3(9):865-870. doi: 10.1001/jamacardio.2018.2093.

  PMID: 30046835 BACKGROUND

• Donnelly JP, Hanna M. Cardiac amyloidosis: An update on diagnosis and treatment. Cleve Clin J Med. 2017 Dec;84(12 Suppl 3):12-26. doi: 10.3949/ccjm.84.s3.02.

  PMID: 29257735 BACKGROUND

• Gilstrap LG, Dominici F, Wang Y, El-Sady MS, Singh A, Di Carli MF, Falk RH, Dorbala S. Epidemiology of Cardiac Amyloidosis-Associated Heart Failure Hospitalizations Among Fee-for-Service Medicare Beneficiaries in the United States. Circ Heart Fail. 2019 Jun;12(6):e005407. doi: 10.1161/CIRCHEARTFAILURE.118.005407. Epub 2019 Jun 7.

  PMID: 31170802 BACKGROUND

Biospecimen

Retention: SAMPLES WITHOUT DNA

Serum samples will be collected and processed for isolation of circulating extracellular vesicles. Aliquots will be stored for proteomic, molecular, and vesicle characterization analyses.

MeSH Terms

Conditions

Amyloid Neuropathies, Familial; Amyloidosis, Familial; Disease

Condition Hierarchy (Ancestors)

Heredodegenerative Disorders, Nervous System; Neurodegenerative Diseases; Nervous System Diseases; Amyloid Neuropathies; Peripheral Nervous System Diseases; Neuromuscular Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Metabolism, Inborn Errors; Metabolic Diseases; Nutritional and Metabolic Diseases; Amyloidosis; Proteostasis Deficiencies; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Felix Jose A Ramires, MD, PhD

CONTACT

+551126615057; felix.ramires@incor.usp.br

Camila R Moreno, PhD

CONTACT

551126615201; camila.moreno@hc.fm.usp.br

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 12 Months
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 25, 2025
• First Posted: January 2, 2026
• Study Start: October 18, 2024
• Primary Completion (Estimated): May 31, 2026
• Study Completion (Estimated): December 31, 2026
• Last Updated: January 2, 2026

Record last verified: 2025-12

Locations

BR (1)