PET/CT Imaging in Carriers of TTR Mutations

Официальное название

Iodine-124 Evuzamitide PET/CT Imaging in Carriers of TTR Mutations

Обзор

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.

Подробное описание

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.

Вмешательства

• Диагностический тест Iodine-124 Evuzamitide (I-124E)
  I-124E is a novel amyloidophilic peptide radiotracer that binds via electrostatic interactions to electronegative glycosaminoglycans and amyloid protein fibrils - both are ubiquitous among amyloid deposits. PET/CT I-124E has acceptable dosimetry estimates and is acceptable for whole-body PET/CT imaging. Data from patients with amyloidosis has established that tracer uptake is present in locations of clinically anticipated amyloid deposits and in locations not clinically appreciated, but also con

Первичные конечные точки

• LV % Injected dose [Срок оценки: PET/CT Scan Visit]

Вторичные конечные точки (12)

• LVFW SUVR, mean [Срок оценки: PET/CT Scan Visit]
• LVFW wall SUVR, max [Срок оценки: PET/CT Scan Visit]
• IVS SUVR, mean [Срок оценки: PET/CT Scan Visit]
• IVS SUVR, max [Срок оценки: PET/CT Scan Visit]
• RVFW SUVR, mean [Срок оценки: PET/CT Scan Visit]
• RVFW SUVR, max [Срок оценки: PET/CT Scan Visit]
• RV % Injected Dose (RV%ID) [Срок оценки: PET/CT Scan Visit]
• LV Cardiac Amyloid Activity (CAA) [Срок оценки: PET/CT Scan Visit]
• LV Target-to-Background Ratio (TBR) [Срок оценки: PET/CT Scan Visit]
• RV Cardiac Amyloid Activity (CAA) [Срок оценки: PET/CT Scan Visit]
• RV Target-to-Background Ratio (TBR) [Срок оценки: PET/CT Scan Visit]
• Left Atrial Uptake [Срок оценки: PET/CT Scan Visit]

Критерии участия

A. Pathogenic TTR Allele Carriers without HF

Inclusion:

• 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

Exclusion:

• 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):

Inclusion:

• 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

Exclusion:

• 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:

Inclusion:

• 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

Exclusion:

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Модель наблюдения

Случай-контроль

Центры проведения

США · 1 центр

• UT Southwestern Medical Center — Dallas

Идентификаторы

NCT: NCT07591038 · STU-2026-0286 · R01HL172993

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗