PET/CT Imaging in Carriers of TTR Mutations (EPIC-TTR)

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

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.

Study Overview

• Status: Not yet recruiting
• Conditions: Cardiomyopathy; Transthyretin Mediated Amyloidosis (ATTR); ATTR Gene Mutation; ATTR
• Intervention / Treatment: Diagnostic test: Iodine-124 Evuzamitide (I-124E)

Detailed Description

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.

• Study Type: Observational
• Enrollment (Estimated): 80

Contacts and Locations

• Study Contact: Name: Amy Browning; Phone Number: 214-645-8040; Email: Amy.Browning@utsouthwestern.edu
• Study Contact Backup: Name: Jerah Sanchez; Phone Number: 214-645-7303; Email: jerahmarie.sanchez@utsouthwestern.edu

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75248
      • UT Southwestern Medical Center
      • Principal Investigator: Justin L Grodin, MD MPH
      • Sub-Investigator: Lori Roth, PA-C
      • Contact: Jerah Sanchez; Phone Number: 214-645-7303; Email: jerahmarie.sanchez@utsouthwestern.edu
      • Sub-Investigator: Vlad Zaha, MD PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

We will enroll 50 carriers of pathogenic TTR alleles without HF, 20 patients with ATTR-CA, and 10-race matched non-carrier controls to have PET/CT I-124E imaging.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Pathogenic TTR Allele Carriers without Heart Failure	Diagnostic test: 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 consistent with the distribution of amyloid in the human body (e.g. heart, kidney, spleen).
Subjects with Symptomatic ATTR-CA	Diagnostic test: 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 consistent with the distribution of amyloid in the human body (e.g. heart, kidney, spleen).
Non-carrier race-matched controls	Diagnostic test: 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 consistent with the distribution of amyloid in the human body (e.g. heart, kidney, spleen).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
LV % Injected dose	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.	PET/CT Scan Visit

Secondary Outcome Measures

Outcome Measure	Time Frame
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

Collaborators and Investigators

• Sponsor: University of Texas Southwestern Medical Center
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Bayer
• Investigators: Principal Investigator: Justin L Grodin, MD MPH, University of Texas Southwestern Medical Center

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): June 30, 2030
• Study Completion (Estimated): June 30, 2030

Study Registration Dates

• First Submitted: May 8, 2026
• First Submitted That Met QC Criteria: May 8, 2026
• First Posted (Actual): May 15, 2026

Study Record Updates

• Last Update Posted (Actual): May 19, 2026
• Last Update Submitted That Met QC Criteria: May 15, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: PET/CT; amyloidosis; transthyretin; TTR; ATTR; evuzamitide; carriers of abnormal gene; TTR gene
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Metabolic Diseases; Proteostasis Deficiencies; Nutritional and Metabolic Diseases; Cardiomyopathies; Amyloidosis
• Other Study ID Numbers: STU-2026-0286; R01HL172993 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes