Subclinical Transthyretin Cardiac Amyloidosis in V122I TTR Carriers

Status Recruiting

Clinical Trial Summary

Approximately 1.5 million of the 44 million Blacks in the United States are carriers of the valine-to-isoleucine substitution at position 122 (V122I) in the transthyretin (TTR) protein. Virtually exclusive to Blacks, this is the most common cause of hereditary cardiac amyloidosis (hATTR-CA) worldwide. hATTR-CA leads to worsening heart failure (HF) and premature death. Fortunately, new therapies that stabilize TTR improve morbidity and mortality in hATTR-CA, especially when prescribed early in the disease. However, hATTR-CA is often diagnosed at an advanced stage and conventional diagnostic tools lack diagnostic specificity to detect early disease. The overall objectives of this study are to determine the presence of subclinical hATTR-CA and to identify biomarkers that indicate amyloid progression in V122I TTR carriers. The central hypothesis of this proposal is that hATTR-CA has a long latency period that will be detected through subclinical amyloidosis imaging and biomarker phenotyping. The central hypothesis will be tested by pursuing 2 specific aims: Aim 1) determine the association of V122I TTR carrier status with CMRI evidence of amyloid infiltration; Sub-aim 1) determine the association of V122I TTR carrier status with cardiac reserve; Aim 2) determine the association between amyloid-specific biomarkers and V122I TTR carrier status; and Sub-aim 2) determine the association of amyloid-specific biomarkers with imaging-based parameters and evaluate their diagnostic utility for identifying subclinical hATTR-CA. In Aim 1, CMRI will be used to compare metrics associated with cardiac amyloid infiltration between a cohort of V122I TTR carriers without HF formed by cascade genetic testing and age-, sex-, and race-matched non-carrier controls. For Sub-Aim 1, a sub-sample of carriers and non-carrier controls enrolled in Aim 1 will undergo novel exercise CMRI to measure and compare cardiac systolic and diastolic reserve. Aim 2 involves measuring and comparing amyloid-specific biomarkers in V122I TTR carriers without HF with samples matched non-carriers (both from Aim 1) and individuals with symptomatic V122I hATTR-CA from our clinical sites. These biomarkers detect and quantify different processes of TTR amyloidogenesis and include circulating TTR, retinol binding protein 4, TTR kinetic stability, and misfolded TTR oligomers. Sub-aim 2 will establish the role of these biomarkers to detect imaging evidence of subclinical hATTR-CA disease.

Clinical Trial Description

n/a

Study Design

Related Conditions & MeSH terms

Amyloidosis
Amyloidosis Cardiac
Amyloidosis, Familial
Amyloidosis, Hereditary
Cardiomyopathies
Transthyretin-Related (ATTR) Familial Amyloid Cardiomyopathy

Clinical Trial Details

NCT number	NCT05489549
Study type	Observational
Source	University of Texas Southwestern Medical Center
Contact	Amy Browning
Phone	214-645-8040
Email	Amy.Browning@utsouthwestern.edu
Status	Recruiting
Phase
Start date	November 21, 2022
Completion date	June 30, 2027

View Details

See also
Status	Clinical Trial	Phase
Not yet recruiting	`NCT04985734` - Transthyretin Amyloidosis Cardiomyopathy (ATTR-CM) in Patients With Idiopathic Peripheral Neuropathy	N/A
Enrolling by invitation	`NCT05718401` - The Diagnostic Pattern and Prognosis of Multiple Myeloma Patients With Myocardial Amyloidosis Were Evaluated by NMR Based Metabolomics
Recruiting	`NCT05167799` - Cardiac Contractility Modulation Therapy in Amyloid Cardiomyopathy Patients With Heart Failure
Completed	`NCT03996382` - Prevalence of Wild Type Transthyretin Cardiac Amyloidosis in Patients Operated for Idiopathic Carpal Tunnel Syndrome	N/A
Recruiting	`NCT06066632` - Analysis of Calcium Score of Severe Aortic Stenosis in Patients With and Without Cardiac Amyloidosis (CAUSATIVE Study)
Recruiting	`NCT05379101` - Intracardiac Flow Assessment in Cardiac Amyloidosis
Recruiting	`NCT06186167` - Amyloidosis Incidence in High-Risk Cardiac Device Patients
Recruiting	`NCT06251778` - NatiOnal Referral cenTEr Study of Transthyretin Amyloid Cardiomyopathy(ATTR) Patients on Tafamidis
Recruiting	`NCT03984877` - Impact of Amyloidosis on TAVI Patients
Completed	`NCT04298372` - Frontline Lenalidomide for AL Amyloidosis Involving Myocardium	Phase 3
Not yet recruiting	`NCT05938218` - Virtual Reality Assisted Patient Empowerment: Diagnose ATTR-Amyloidosis And Start Treatment	N/A
Recruiting	`NCT04667494` - Ultrasound Therapy In Cardiac Amyloidosis	Phase 4
Active, not recruiting	`NCT04061213` - ATTR Amyloidosis in Elderly Patients With Aortic Stenosis
Recruiting	`NCT04587648` - Cardiac Amyloidosis in HFpEF

Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.

Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
Phase 3: The drug or treatment is given to large groups of people to confirm its effectiveness, monitor side effects, compare it to commonly used treatments, and collect information that will allow the drug or treatment to be used safely.
Phase 4: Studies are done after the drug or treatment has been marketed to gather information on the drug's effect in various populations and any side effects associated with long-term use.