Determining the Association of TTR Stabilizing Therapy With Circulating TTR Amyloid Aggregates Over Time in Patients With ATTR-CM: Longitudinal Biomarker Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 50
- 试验地点
- 2
- 主要终点
- Serial blood levels of circulating TTR amyloid aggregates (TAAs)
研究概览
简要总结
The objective of this study is to determine the association of clinically prescribed, on-label, TTR stabilizing therapy (e.g. tafamidis or acoramidis) with levels of circulating transthyretin amyloid aggregates (TAAs, a surrogate for amyloid disease activity) measured serially over time in patients with transthyretin cardiac amyloidosis (ATTR-CA). To accomplish this objective, the hypothesis that TTR stabilizing therapy will be associated lower circulating TAAs over time will be tested. Completion of this study will advance the understanding of the influence of ATTR-CA treatments on circulating evidence of amyloidosis and justify the role of blood testing to monitor treatment response in patients with ATTR-CA.
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
- 30 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Men and women ages 30-80 who have symptomatic ATTR-CA as determined by a history of HF (this will be assessed by study personnel and defined as : 1) history of hospitalization within the previous 12 months for management of HF; 2) an elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the previous 12 months; or 3) a clinical diagnosis of HF from a treating clinician)
- •ATTR-CA previously diagnosed histologically by amyloid staining and tissue typing with immunohistochemistry or mass spectrometry or by bone scintigraphy in without abnormal M-protein
- •TTR gene sequencing confirming the TTR genotype has resulted or is pending
- •Enrollment will be stratified by n/N=30/50 starting on-label TTR-stabilizing therapy (e.g. tafamidis) within 5 days after enrollment or by n/N=20/50 of those currently taking TTR-stabilizing therapy
排除标准
- •Other known causes of cardiomyopathy
- •History of light-chain cardiac amyloidosis
- •Cardiac transplantation
- •Liver transplantation
- •Has taken patisiran in the past 90 days, or inotersen in the past 180 days, has ever taken vutrisiran, or is participating in a clinical trial for ATTR treatments
- •Estimated glomerular filtration rate ≤30 mL/min/1.73 m2
- •Anticipated gaps in ATTR-CA treatment for 3 months after enrollment
结局指标
主要结局
Serial blood levels of circulating TTR amyloid aggregates (TAAs)
时间窗: Baseline, 1 month (+/- 5 days), and 3 months (+/- 5 days).
The primary hypothesis is that TTR stabilizing therapy will lower circulating evidence of amyloidosis in patients with ATTR-CA from baseline to 3 months. In addition, the study team expects that there will be a time\*treatment interaction identifying that treatment initiation will have a differential effect on serial levels of circulating s over time than those currently on treatment. These observations will support the role for measuring circulating TAAs to monitor treatment response in ATTR-CA.
次要结局
未报告次要终点
研究者
Justin Grodin
Associate Professor of Medicine
University of Texas Southwestern Medical Center