NCT05489549Recruiting
Subclinical Transthyretin Cardiac Amyloidosis in V122I TTR Carriers
Identifying Subclinical Transthyretin Cardiac Amyloidosis in Asymptomatic Carriers of the V122I TTR Allele
Source: ClinicalTrials.gov · Last updated 31 Aug 2026
Brief summary (registry, in English)
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.
- Status (registry)
- Recruiting
- Study type
- Observational
- Enrollment
- 500 (estimated)
- First submitted
- 29 Jul 2022
- Start date
- 21 Nov 2022
- Primary completion date
- 30 Jun 2027
- Lead sponsor
- University of Texas Southwestern Medical Center
- Diseases
- Amyloidosis
- NCT number
- NCT05489549
What you commit to
- Study type: Observational
- Planned participants: 500
- From 21 Nov 2022 to the primary completion date, 30 Jun 2027
- 3 sites in 1 country
- Visits and tests: ask the trial team, the registry does not list them
Built from the registry fields of ClinicalTrials.gov. It describes the study, not your situation.
Who cannot take part
Copied verbatim from ClinicalTrials.gov and grouped by topic. Only the trial team decides who can take part.
Prior treatment
- Prior type 1 myocardial infarction (non-ST segment elevation myocardial Infarction {NSTEMI} or ST-elevation myocardial infarction {STEMI})
- Liver transplantation
- Previous treatment with a TTR stabilizer (tafamidis, acoramidis) within the prior 14 days or TTR any silencer (inotersen, patisiran, eplontersen)
Other illness
- A self-reported history or clinical history of HF
- History of light-chain cardiac amyloidosis
- Cardiac transplantation
- History of light-chain cardiac amyloidosis
- Cardiac transplantation
Other
- Other known causes of cardiomyopathy
- 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.)
- Other known causes of cardiomyopathy
- Estimated glomerular filtration rate ≤30 mL/min/1.73 m2
Who the study is looking for
- 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
- 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
Criteria the registry did not label
- (V122I TTR carriers and carriers of other pathogenic TTR alleles (or matched non-carriers))
Age in the registry: 30 years to 80 years · Sex: All
Sites (3)
Sites in registry order. Pick your city on the disease page to sort them by distance.
| Site | City | Country | Site status |
|---|---|---|---|
| Cleveland Clinic Coordinator of this site? Confirm its status | Cleveland | United States | Recruiting |
| University of Texas Southwestern Medical Center Coordinator of this site? Confirm its status | Dallas | United States | Recruiting |
| Columbia University Medical Center Coordinator of this site? Confirm its status | New York | United States | Recruiting |
This page is information, not medical advice. Discuss any trial with your doctor.