ClinicalTrials.gov record NCT05489549

Subclinical Transthyretin Cardiac Amyloidosis in V122I TTR Carriers

Record copied from ClinicalTrials.gov: Oct 10, 2026AI summaries generated: Sep 17, 2026

Identifying Subclinical Transthyretin Cardiac Amyloidosis in Asymptomatic Carriers of the V122I TTR Allele

StatusRecruitingThe study is currently enrolling participants. Only the study team can say whether a particular person can join.
Study typeObservationalA study in which researchers do not assign participants to a treatment or other intervention. They observe or measure what happens, which may include study visits, tests, questionnaires or a review of medical records.
Age30 years old to 80 years old
SexAll
LocationUnited States
AI summaryWhat this study is about, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

This observational, case-control study looks for early (subclinical) transthyretin cardiac amyloidosis in people who carry the V122I TTR gene variant, compares them with matched non-carrier controls, and includes a group with symptomatic V122I hATTR-CA. Carriers and their matched non-carrier controls will have a baseline cardiac MRI; a subset at UT Southwestern will also have exercise cardiac MRI during the same visit, and all groups will provide blood samples for biomarker testing. The study is cross-sectional and compares imaging and biomarker results between the groups.

What it is studying. Whether V122I TTR carriers show imaging evidence of cardiac amyloid before symptoms, and which blood biomarkers are associated with imaging findings and symptomatic disease.

What the researchers hope to learn. Determine whether subclinical cardiac amyloid can be detected by cardiac MRI in V122I TTR carriers; assess cardiac reserve using exercise MRI; measure and evaluate amyloid-specific blood biomarkers (including circulating TTR, RBP4, misfolded TTR oligomers, and TTR kinetic stability) for associations with imaging and their diagnostic utility.

What this study is about

The study's own summary, as published on ClinicalTrials.gov. Underlined terms have a short explanation.

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.

Eligibility

The criteria exactly as listed on ClinicalTrials.gov. Only the study team can say whether they apply to you.

Inclusion criteria

  • (V122I TTR carriers and carriers of other pathogenic TTR alleles (or matched non-carriers))
  • 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.)
  • 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
  • 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 description and what participation involves

The registry record has no detailed description beyond the summary above.

AI summaryWhat participation may involve, in plain languageShow ▾Hide ▴

AI-written from the registry record, not the study's own wording. May contain errors or omissions. Check the registry text on this page and the original record ↗ before acting on it.

Carriers and matched non‑carrier controls will undergo a detailed cardiac MRI (CMRI) exam to look for early amyloid changes. A sub‑group at UT Southwestern will also have exercise CMRI, exercising inside the MRI on an MR‑compatible ergometer with imaging at rest and during staged exercise. All participants (and a separate group of people with symptomatic V122I hATTR‑CA) will have blood drawn by phlebotomy for storage and measurement of amyloid-specific biomarkers. Some CMRI sequences involve injected gadolinium contrast.

How the study is structured. This is a cross-sectional, observational case-control study. It enrolls V122I (pathogenic TTR) carriers without heart failure, age/sex/race-matched non-carrier controls, and patients with symptomatic V122I hATTR-CA. At a baseline visit, carriers and matched non-carrier controls undergo standardized cardiac MRI; a subset at UT Southwestern also undergoes exercise cardiac MRI during the same visit. Venous blood is collected once at enrollment for multiple amyloid-related biomarker measurements. Results from the three groups are compared.

Questions you could ask

These questions are suggestions for a conversation with the study team or your own clinician, not advice.

  • This is an observational study, so the study itself gives no treatment. What would taking part involve for me, and would it change my usual care?
  • The listed sites are in United States. Is any of them reachable for me, and does the study help with travel?
  • Which of the eligibility criteria would need to be checked with tests before I could join?

More on ATTRv amyloidosis

This trial is also listed on this site under wild-type ATTR amyloidosis.

Clinical trials106 trials listed for ATTRv amyloidosisEvery trial the registry lists for ATTRv amyloidosis, with recruitment status, phase and sites, updated from ClinicalTrials.gov.See all trials →Research updatesWhat changed in ATTRv amyloidosis researchLatest monthly update: September 2026. Includes: Gene-silencing drugs. New research summarized each month in plain language, with links to every source paper.Read the latest update →

Important dates

Study start
Nov 21, 2022
Primary completion
Jun 30, 2027 (estimated)
Study completion
Jun 30, 2027 (estimated)
Target enrollment
500 participants (estimated)
Last updated on registry
Aug 31, 2026
Data verified
Oct 10, 2026

Sponsor and research team

The lead sponsor funds and oversees the trial. A pharmaceutical or biotech company sponsor typically means the study is testing that company's drug or device; a hospital, university, or government agency usually indicates investigator-initiated or publicly funded research.

Lead sponsor
University of Texas Southwestern Medical Center
Principal investigator
Justin Grodin, Associate Professor of Medicine
University of Texas Southwestern Medical Center
Collaborators
  • The Cleveland Clinic
  • Columbia University
  • The University of Texas at Arlington
  • National Heart, Lung, and Blood Institute (NHLBI)

Central study contact

If you're interested in participating, the central contact can answer general questions about the study — including eligibility requirements and how to find a recruiting site near you. Actual eligibility is determined by the site's medical team.

Participating sites (3)

  • Columbia University Medical CenterRecruiting

    New York, New York, 10032 · United States

  • Cleveland ClinicRecruiting

    Cleveland, Ohio, 44195 · United States

  • University of Texas Southwestern Medical CenterRecruiting

    Dallas, Texas, 75390 · United States

Terms used on this page · explanations by MedicalUpdates.ai

biomarkers
Something measurable in the body, such as a blood test result or an imaging finding, that indicates how a condition or treatment is behaving.
cohort
A group of people who share a characteristic, such as a diagnosis, and are studied together. 'Prospective' means they are followed forward from enrolment; 'retrospective' means existing records are reviewed.
informed consent
The process of explaining a study, including its risks and what participation involves, so that a person can decide freely whether to take part. Consent is usually documented in writing, and a participant can choose to leave the study later.
Estimated glomerular filtration rate
A blood-test estimate of how well the kidneys are filtering. Lower numbers mean reduced kidney function; many studies set a minimum value.
Biopsy
Removal of a small piece of tissue so it can be examined under a microscope. 'Biopsy-proven' or 'histologically confirmed' means the diagnosis was confirmed by examining tissue under a microscope.
Inclusion Criteria
The conditions a person must meet to be considered for the study, for example a confirmed diagnosis, an age range or a test result.
Exclusion Criteria
The conditions that rule a person out even if they meet the inclusion criteria, for example other illnesses, certain medicines or pregnancy.

The study record on this page is reproduced from ClinicalTrials.gov, a database of the U.S. National Library of Medicine, where it was submitted by the study sponsor. MedicalUpdates.ai does not own this content, is not affiliated with or endorsed by ClinicalTrials.gov, NIH, or the U.S. Government, and does not verify the record. Plain-language notes, the glossary and the questions above are added by this site; text in the boxes marked "AI summary" was written by an AI model and may contain errors. Registry records change over time. Check the original record for the current version and discuss eligibility or participation with a qualified healthcare professional.

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