ATTR Amyloid Cardiomyopathy: Characterization of Extracellular Vesicles as Potential Disease Stratifiers and Prognostic Biomarkers
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 70
- 试验地点
- 1
- 主要终点
- Circulating extracellular vesicle protein profile
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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.
排除标准
- •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.
结局指标
主要结局
Circulating extracellular vesicle protein profile
时间窗: 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.
Serum concentration of circulating extracellular vesicles (EVs)
时间窗: 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.
次要结局
- 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)
研究者
FELIX JOSÉ ALVAREZ RAMIRES
Principal Investigator
University of Sao Paulo General Hospital