Iodine-124 Evuzamitide PET/CT Imaging in Carriers of TTR Mutations
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 80
- 试验地点
- 1
- 主要终点
- LV % Injected dose
研究概览
简要总结
The purpose of this study is to determine if TTR gene carriers have early signs of a type of heart disease called amyloidosis using a new radiotracer dye (iodine-124 evuzamitide, I-124E).
Participants will undergo a screening that includes a medical history review and completion of quality-of-life surveys. Once screening is complete, participants will undergo an imaging test called a positron emission tomography (PET) scan combined with computed tomography (PET/CT) to make images of the body. The new radiotracer dye (I-124E, a radioactive contrast) will be used during the PET/CT to make amyloidosis visible in the heart and body.
详细描述
This will be a cross-sectional cohort study of 50 carriers of pathogenic TTR alleles without HF; 10-race matched non-carrier controls; and 20 patients with ATTR-CA. Participants will undergo standardized, PET/CT direct amyloid imaging assessments with I-124E to test the hypothesis that carriers of pathogenic TTR alleles without HF will have LV%ID intermediate to non-carrier controls and patients with ATTR-CA. This will address the fundamental questions of whether and to what extent cardiac amyloid infiltration is present in carriers of pathogenic TTR alleles prior to ATTR-CA disease onset.
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Cross Sectional
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
- 是
入选标准
- •A. Pathogenic TTR Allele Carriers without HF
- •men and women ages 30-80 who are pathogenic allele TTR carriers without history of HF (this will be assessed by study personnel and defined as : 1) No history of hospitalization within the previous 12 months for management of HF; 2) Without 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)
- •have already completed the protocol for NCT05489549 at UT Southwestern only
排除标准
- •a self-reported history or clinical history of HF
- •other known causes of cardiomyopathy
- •history of light-chain cardiac amyloidosis
- •prior type 1 myocardial infarction
- •cardiac transplantation
- •liver transplantation
- •body weight or habitus that exceeds the site-specific PET/CT parameters
- •estimated glomerular filtration rate ≤30 mL/min/1.73 m2
- •inability to safely undergo PET/CT
- •participating in a clinical trial for ATTR treatments or taking a fibril deleting agent
- •pregnancy or breastfeeding
- •patients taking heparin or heparin derivatives for anticoagulation
- •allergy to potassium iodide
- •known uncorrected thyroid disorder
- •B. Subjects with symptomatic hATTR-CA (may be supplemented with other ATTR-CA genotypes including wild-type in the occasion of slow enrollment):
- •men and women ages 30-80 who have symptomatic V122I hATTR-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)
- •hATTR-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 variant
- •have already completed the protocol for NCT05489549 at UT Southwestern only
- •other known causes of cardiomyopathy
- •history of light-chain cardiac amyloidosis
- •cardiac transplantation
- •liver transplantation
- •history of type I myocardial infarction
- •body weight or habitus that exceeds the site-specific PET/CT parameters
- •estimated glomerular filtration rate ≤30 mL/min/1.73 m2
- •inability to safely undergo PET/CT
- •participating in a clinical trial for ATTR treatments or taking a fibril deleting agent
- •patients taking heparin or heparin derivatives for anticoagulation
- •pregnancy or breastfeeding
- •allergy to potassium iodide
- •known uncorrected thyroid disorder
- •C. Non-carrier race-matched controls:
- •men and women ages 30-80 who are non-carriers without history of HF (this will be assessed by study personnel and defined as: 1) No history of hospitalization within the previous 12 months for management of HF; 2) Without an elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the previous 12 months; or 3) No clinical diagnosis of HF from a treating clinician
- •have previously enrolled in the Dallas Heart Study
- •a self-reported history or clinical history of HF
- •other known causes of cardiomyopathy
- •history of light-chain cardiac amyloidosis
- •prior type 1 myocardial infarction
- •cardiac transplantation
- •liver transplantation
- •body weight or habitus that exceeds the site-specific PET/CT parameters
- •estimated glomerular filtration rate ≤30 mL/min/1.73 m2
- •inability to safely undergo PET/CT
- •participating in a clinical trial for ATTR treatments or taking a fibril deleting agent
- •patients taking heparin or heparin derivatives for anticoagulation
- •pregnancy or breastfeeding
- •allergy to potassium iodide
- •known uncorrected thyroid disorder
研究组 & 干预措施
Pathogenic TTR Allele Carriers without Heart Failure
干预措施: Iodine-124 Evuzamitide (I-124E) (Diagnostic Test)
Subjects with Symptomatic ATTR-CA
干预措施: Iodine-124 Evuzamitide (I-124E) (Diagnostic Test)
Non-carrier race-matched controls
干预措施: Iodine-124 Evuzamitide (I-124E) (Diagnostic Test)
结局指标
主要结局
LV % Injected dose
时间窗: PET/CT Scan Visit
Evidence of subclinical cardiac amyloid infiltration as measured by PET/CT quantification imaging with I-124E. This will be defined as LV % injected dose (LV%ID = volume of interest \[VOI\] mean activity concentration in the LV X VOI volume / injected activity). LV%ID is an ideal metric to assess cardiac amyloid burden because it is: 1) correlated with validated metrics assessing cardiac amyloid burden; 2) sensitive for detection of early disease (patchy vs. diffuse uptake); and 3) highly repeatable and standardizable to other metrics of radiotracer uptake. LV%ID is adjusted for injected activity, but not for body weight, because the latter is unnecessary for a radiotracer accumulating in the heart and specific organs, not in the whole body.
次要结局
- LVFW SUVR, mean(PET/CT Scan Visit)
- LVFW wall SUVR, max(PET/CT Scan Visit)
- IVS SUVR, mean(PET/CT Scan Visit)
- IVS SUVR, max(PET/CT Scan Visit)
- RVFW SUVR, mean(PET/CT Scan Visit)
- RVFW SUVR, max(PET/CT Scan Visit)
- RV % Injected Dose (RV%ID)(PET/CT Scan Visit)
- LV Cardiac Amyloid Activity (CAA)(PET/CT Scan Visit)
- LV Target-to-Background Ratio (TBR)(PET/CT Scan Visit)
- RV Cardiac Amyloid Activity (CAA)(PET/CT Scan Visit)
- RV Target-to-Background Ratio (TBR)(PET/CT Scan Visit)
- Left Atrial Uptake(PET/CT Scan Visit)
- Right Atrial Uptake(PET/CT Scan Visit)
- Liver Uptake(PET/CT Scan Visit)
- Spleen Uptake(PET/CT Scan Visit)
- Kidney Uptake(PET/CT Scan Visit)
研究者
Justin Grodin
Associate Professor
University of Texas Southwestern Medical Center