Southeastern ATTR Amyloidosis Consortium: SEATTRAC Family Registry

The study design is a prospective registry including asymptomatic and symptomatic patients who carry a pathogenic TTR mutation. The study will enroll patients who meet the inclusion criteria and none of the exclusion criteria until 1000 patients are enrolled, at which point in time the study investigators will evaluate whether further patient accrual is meaningful.

Study Overview

• Status: Not yet recruiting
• Conditions: Amyloidosis, Hereditary
• Intervention / Treatment: Other: Registry

Detailed Description

Hereditary transthyretin amyloidosis (hATTR) is an autosomal dominant disorder caused by a pathogenic mutation of the transthyretin (TTR) gene. The mutated gene destabilizes the TTR tetramer causing it to dissociate, misfold and accumulate as insoluble extracellular amyloid fibrils. These fibrils then deposit in various organs and tissues leading to organ dysfunction and destruction. There are more than 130 known pathogenic mutations of the TTR gene leading to hATTR with predominantly neurologic or cardiac clinical manifestations.

The V142I mutation (historically reported as V122I prior to the opening 20-amino acid sequence being included to the position count) is the most prevalent mutation in the United States. This mutation is carried by 3-4% of the Black population with a founder variant originating in West Africa. It was brought to the Western Hemisphere during the Atlantic slave trade. The presence of the mutation has been associated with increased risk of heart failure, however with incomplete penetrance of an amyloid cardiomyopathy phenotype. With improved accessibility to genetic testing and noninvasive techniques with bone scintigraphy to diagnose TTR deposition in the heart, the identification of disease has dramatically increased. As a result, genetic counseling and cascade testing has identified a growing pool of asymptomatic, at-risk family members for whom counseling and surveillance is undefined.

There is a paucity of data for V142I carriers including poor understanding of disease penetrance, timing of disease onset as well as onset of extracardiac manifestations. Prior studies that sought to understand disease penetrance and early clinical predictors of phenotype presentation were limited due to geographic variation, historical under-recognition of the disease, poor enrollment of Black V142I patients into clinical studies and missing data due to retrospective study designs. For example, the often-cited THAOS (Transthyretin Amyloidosis Outcomes Survey) registry demonstrated enrollment limitations. Of the 740 total asymptomatic hATTR mutation carriers studied, only 10 asymptomatic subjects had the V142 mutation.

Better described neuropathic or mixed variants (i.e. T80A [formerly T60A] and V50M [formerly V30M] are often associated with easily detectable, clinically debilitating and rapidly progressing disease earlier in life. Conversely the V142I phenotype presents later in life primarily with a cardiomyopathy that may mimic hypertensive heart disease or heart failure with preserved ejection fraction. Oftentimes symptoms in the older V142I patient population are attributed to other comorbidities such as diabetes, hypertension or valve disease. This contributes to a delay in the diagnosis of hATTR diagnosis or a miss altogether. Identifying early clinical predictors of disease presentation may offer an opportunity for meaningful interruption of disease progression with newly available disease modifying therapies.

In this study, members of the Southeastern ATTR Amyloidosis Consortium (SEATTRAC) will enroll asymptomatic carriers of pathogenic TTR mutations and hATTR cardiac amyloidosis patients in a prospective registry. SEATTRAC members include high volume amyloidosis centers that are not only destination centers for amyloidosis care, but comprehensively serve their local and regional communities. We anticipate that such a registry will be the first to describe the clinical course of disease and outcomes for asymptomatic carriers of the V142I mutation, the hATTR variant that predominantly afflicts Black Americans.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Keyur Shah, MD; Phone Number: 804-828-4571; Email: keyur.shah@vcuhealth.org
• Study Contact Backup: Name: Sarah Paciulli, NP; Phone Number: 804-828-4571; Email: sarah.paciulli@vcuhealth.org

Study Locations

• United States
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Virginia Commonwealth University
      • Contact: Keyur Shah, MD; Phone Number: 804-828-4571; Email: keyur.shah@vcuhealth.org
      • Principal Investigator: Keyur Shah, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Any carriers of a pathogenic TTR mutation known to cause hATTR amyloidosis will be recruited to the registry.

Description

Inclusion Criteria:

• Over the age of 18 years
• Carrier of a pathogenic hATTR mutation confirmed on whole blood gene testing or mass spectrometry
• Willing to return for required follow-up visits

Exclusion Criteria:

• Patient having undergone heart transplantation or implantation of mechanical circulatory support
• Patients unable to provide informed consent
• Patients having undergone liver transplantation
• Patients have evidence of light chain amyloidosis

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Asymptomatic carriers	Other: Registry; The purpose of this registry is to collect and store health information from people who are carriers of the gene known to cause hereditary amyloidosis and those with a confirmed diagnosis of the disease.
Patients with cardiac hereditary transthyretin amyloidosis (hATTR)	Other: Registry; The purpose of this registry is to collect and store health information from people who are carriers of the gene known to cause hereditary amyloidosis and those with a confirmed diagnosis of the disease.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The predictors and incidence of amyloidosis	For those enrolled as asymptomatic carriers, it will be assessed if they develop cardiac or extra cardiac amyloidosis	15 years
Mortality and/or need for heart transplant	For those with cardiac hereditary transthyretin amyloidosis (hATTR), it will be assessed how many participants die due to disease or require a heart transplant	10 years

Collaborators and Investigators

• Sponsor: Virginia Commonwealth University
• Investigators: Principal Investigator: Keyur Shah, MD, Virginia Commonwealth University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 1, 2030
• Study Completion (Estimated): December 1, 2030

Study Registration Dates

• First Submitted: July 14, 2023
• First Submitted That Met QC Criteria: July 25, 2023
• First Posted (Actual): August 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 8, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolism, Inborn Errors; Genetic Diseases, Inborn; Metabolic Diseases; Proteostasis Deficiencies; Amyloidosis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Nutritional and Metabolic Diseases; Amyloidosis, Familial; Organization and Administration; Health Services Administration; Health Care Quality, Access, and Evaluation; Investigative Techniques; Epidemiologic Methods; Data Collection; Health Care Evaluation Mechanisms; Quality of Health Care; Public Health; Environment and Public Health; Records; Registries
• Other Study ID Numbers: HM20027103

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Deidentified data will be provided to the other investigators as a limited data set if requested.
• IPD Sharing Time Frame: Duration of the registry
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No