Recruiting

Transthyretin Cardiac Amyloidosis

Sponsor:

University of Texas Southwestern Medical Center

Code:

NCT05489549

Conditions

Amyloidosis, Hereditary

Amyloidosis Cardiac

Amyloidosis, Familial

Transthyretin-Related (ATTR) Familial Amyloid Cardiomyopathy

Transthyretin Gene Mutation

Eligibility Criteria

Sex: All

Age: 30 - 70+

Healthy Volunteers: Not accepted

Study Details

Brief 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.

Conditions

Amyloidosis, Hereditary

Amyloidosis Cardiac

Amyloidosis, Familial

Transthyretin-Related (ATTR) Familial Amyloid Cardiomyopathy

Transthyretin Gene Mutation

Study ID

NCT05489549

Start date

Nov 21, 2022

Status verified date

Jun, 2026

Completion date

Jun 30, 2027

Anticipated

Primary completion date

Jun 30, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 30 - 70+

Healthy Volunteers: Not accepted

(V122I TTR carriers and carriers of other pathogenic TTR alleles (or matched non-carriers))

Inclusion Criteria:

  • Men and women ages 30-80 who are carriers of pathogenic TTR alleles (or matched non-carriers) without history of HF (this will be assessed by study personnel) and defined as: a) No history of hospitalization within the previous 12 months for management of HF; b) Without an elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the previous 12 months; or c) No clinical diagnosis of HF from a treating clinician
  • Signed informed consent

Exclusion Criteria:

  • 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 (non-ST segment elevation myocardial Infarction {NSTEMI} or ST-elevation myocardial infarction {STEMI})
  • Cardiac transplantation
  • Body weight >250 lbs
  • Estimated glomerular filtration rate ≤30 mL/min/1.73 m2
  • Inability to safely undergo CMRI

(For participants with symptomatic hATTR-CA, we will enroll probands with HF from Aim 1 or patients with suspected symptomatic hATTR-CA from the three study sites.)

Inclusion Criteria:

  • Men and women ages 30-80 who have symptomatic hATTR-CA as determined by a history of HF (this will be assessed by study personnel) and defined as: a) History of hospitalization within the previous 12 months for management of HF; b) An elevated B-type natriuretic peptide level ≥100 pg/mL or NT-proBNP ≥360 pg/mL within the previous 12 months; or c) A clinical diagnosis of HF from a treating clinician.
  • Have an established or suspected diagnosis of hATTR-CA based on either a) Biopsy confirmed by Congo red (or equivalent) staining with tissue typing with immunohistochemistry or mass spectrometric analysis or immunoelectron microscopy, OR b) positive technetium-99m (99mTc)-pyrophosphate or -bisphosphonate scan, combined with accepted laboratory criteria without abnormal M-protein.
  • TTR gene sequencing that is pending or that is confirming the pathogenic TTR variant
  • Signed informed consent

Exclusion Criteria:

  • Other known causes of cardiomyopathy
  • History of light-chain cardiac amyloidosis
  • Cardiac transplantation
  • Liver transplantation
  • Previous treatment with a TTR stabilizer (tafamidis, acoramidis) within the prior 14 days or TTR any silencer (inotersen, patisiran, eplontersen)
  • Estimated glomerular filtration rate ≤30 mL/min/1.73 m2

Study Design

Enrollment

500 participants

Anticipated

Interventions and Outcome Measures

Arms

V122I TTR carriers

Carriers and controls will undergo standardized, detailed CMRI assessments to test the hypothesis that V122I TTR carrier status will be associated with greater evidence of pathological amyloid progression in comparison with non-carriers.

In addition to the CMRI assessments, carriers and controls enrolled at UT Southwestern will undergo standardized exercise CMRI assessments during the same study visit.

V122I TTR carriers will undergo detailed biomarker assessments. These will be compared with controls and patients with symptomatic V122I hATTR-CA .

Age-, sex-, and race-matched non-carrier controls

Carriers and controls will undergo standardized, detailed CMRI assessments to test the hypothesis that V122I TTR carrier status will be associated with greater evidence of pathological amyloid progression in comparison with non-carriers.

In addition to the CMRI assessments, carriers and controls enrolled at UT Southwestern will undergo standardized exercise CMRI assessments during the same study visit.

Controls will undergo detailed biomarker assessments. These will be compared with V122I TTR carriers and patients with symptomatic V122I hATTR-CA .

Patients with symptomatic V122I hATTR-CA

Patients with symptomatic V122I hATTR-CA will undergo detailed biomarker assessments. These will be compared with V122I TTR carriers and controls.

Primary outcome measure

  • (Aim 1) Evidence of amyloid infiltration as measured by ECV [ Time Frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls) ]
  • (Sub-aim 1) Δ stroke volume index (ΔSVi) [ Time Frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls) enrolled at UT Southwestern ]

Central Contacts and Locations

Central contacts

Amy Browning

214-645-8040Amy.Browning@utsouthwestern.edu

Lori R Roth, MS, PAC

214-645-1043Lori.Roth@utsouthwestern.edu

Locations

Columbia University Medical Center

Recruiting

New York, New York, United States, 10032

Contacts

Jeffeny De Los Santos, MHA

(212) 932-4047jd3456@cumc.columbia.edu

Principal Investigator:

Mathew S Maurer, MD

Cleveland Clinic

Recruiting

Cleveland, Ohio, United States, 44195

Contacts

Jennifer (Kirsop) Wilcox

216-636-6153kirsopj@ccf.org

216-636-6153

Principal Investigator:

W. H. Wilson Tang, MD

University of Texas Southwestern Medical Center

Recruiting

Dallas, Texas, United States, 75390

Contacts

Amy Browning

214-645-8040Amy.Browning@utsouthwestern.edu

Principal Investigator:

Justin L Grodin, MD MPH

More Information

Sponsor

University of Texas Southwestern Medical Center

Last update posted

Aug 31, 2026

Last verified

Jun, 2026

Keywords

  • Amyloidosis
  • Transthyretin Amyloidosis
  • V122I TTR
  • p.Val142Ile TTR
  • Cardiac magnetic resonance imaging

Trial information was received from ClinicalTrials.gov and was last updated on 2026-10-10. This information was provided to ClinicalTrials.gov by University of Texas Southwestern Medical Center on 2026-08-31. Recruitment status is synced daily from ClinicalTrials.gov and may not reflect the sponsor's current status. Confirm during your call.