Genetic Screening of an At-risk Population for Hereditary TransthyRetin-related AMyloidosis and Longitudinal Monitoring of TTR Positive Subjects- A Multicenter Epidemiological Longitudinal Protocol
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- 入组人数
- 5,028
- 试验地点
- 83
- 主要终点
- Analysis of prevalance of hATTR mutations among a cohort of participants at risk for hATTR.
研究概览
简要总结
National, multicenter, epidemiological, longitudinal protocol to investigate the hATTR prevalence in an at-risk population for Hereditary Transthyretin Amyloidosis (hATTR) and subjects diagnosed with hATTR, to monitor the clinical status in TTR positive subjects and to establish hATTR biomarker/s
详细描述
Hereditary TransThyRetin Amyloidosis (hATTR) is a slowly progressive condition, that is transmitted as an autosomal dominant trait and is characterized by abnormal extracellular deposits of fibrillar, misfolded proteins (amyloid fibrils) in the body. Amyloid fibrils can be deposited in different body compartments, such as the nerves, heart, gastrointestinal tract, kidneys and brain, causing severe structural changes. More than 30 proteins can trigger the formation of amyloid fibrils, 5 of which can infiltrate the heart and cause cardiac amyloidosis.
One of these amyloidogenic protein is transthyretin, formerly known as prealbumin. Transthyretin (TTR) is found primarily in the serum (secreted by the liver) and cerebrospinal fluid (secreted by the choroid plexus) and functions as a carrier for the hormone thyroxine (T4) and retinol-binding protein (bound to retinol or vitamin A). The destabilization of the TTR protein and the formation of misfolded TTR.
It is the goal of this study to investigate the prevalence of Hereditary Transthyretin-related Amyloidosis (hATTR) in a cohort of 5.000 subjects are at risk for Hereditary Transthyretin Amyloidosis (hATTR) and subjects diagnosed with hATTR, to monitor the clinical status in TTR positive subjects and to establish hATTR biomarker/s.
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
- 否
入选标准
- •Informed consent is obtained from the participant
- •The participant is 18 years of age or older
- •The participant has no diagnosis of alcoholism according to international guidelines
- •The participant has not undergone chemotherapy for any carcinoma
- •The participant is at risk for hATTR due to two or more the factors listed below:
- •cardiomyopathy or polyneuropathy with no obvious etiology atypical Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) or Motor Neuron Disease (MND)
- •autonomic dysfunction
- •hypertrophic cardiomyopathy or heart failure with preserved ejection fraction Left Ventricular Hypertrophy (LVH)
- •bilateral carpal tunnel syndrome
- •spinal stenosis or spinal radiculopathy
- •gait disorders
- •ocular changes involving vitreous opacities
- •unexplained weight loss >5kg
- •renal abnormalities
- •family history of hATTR
- •based on imaging or biopsy suspected for the wild type TTR (ATTR) and not genetically tested for hATTR
- •OR • The participant is diagnosed with hATTR
- •The participant is a 1st or 2nd degree relative of the TTR positive subject
- •Exclusion Criteria
- •Informed consent is not obtained from the participant
- •The participant is younger than 18 years of age
- •The participant has a diagnosis of alcoholism according to International guidelines
- •The participant has undergone chemotherapy for any carcinoma
- •The participant is not at risk for hATTR
排除标准
- 未提供
结局指标
主要结局
Analysis of prevalance of hATTR mutations among a cohort of participants at risk for hATTR.
时间窗: 4 years
DBS-based genetic analyses of TTR gene will be perfomed via the combination of the Next-Generation Sequencing (the mutation will be confirmed by Sanger sequencing) and the Multiplex ligation-dependent probe amplification.
To monitor clinical status in TTR positive subjects.
时间窗: 4 years
8 Follow up visits within 24 months
次要结局
- Establishment of biomarker/s in TTR positive cohort.(4 years)