An observational study in Amyloidosis, Hereditary, Amyloidosis Cardiac and Amyloidosis, Familial, sponsored by University of Texas Southwestern Medical Center. Recruiting at 3 sites in United States. Open to participants aged 30 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-08-31.
Sponsored by University of Texas Southwestern Medical Center · Observational
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.
28 studies on the registry are indexed under Amyloidosis, Familial; 10 are open to participants now.
This study's planned enrollment of 500 is above the median of 70 across 11 observational studies indexed under Amyloidosis, Familial.
Browse Amyloidosis, Familial studies →University of Texas Southwestern Medical Center is the lead sponsor of 1,010 studies on the registry; 199 are open to participants now.
Of its 139 completed or terminated interventional studies of FDA-regulated products, 105 (76%) have results posted.
Counted across the registry records on this site, refreshed daily.
For Aim 1, the will be a cross-sectional cohort study of 200 pathogenic TTR allele carriers and 200 age-, sex- and race-matched non-carrier controls without heart failure.
For Sub-aim 1, this will be a cross-sectional sub-study of the 2 groups enrolled in Aim 1 at UT Southwestern.
For Aim 2, this will be a cross-sectional cohort study of 200 pathogenic TTR allele carriers without HF (see Aim 1, Approach), 200 age-, sex-, and race-matched controls (see Aim 1), and 100 patients with symptomatic hATTR-CA who will undergo detailed biomarker assessments.
(V122I TTR carriers and carriers of other pathogenic TTR alleles (or matched non-carriers))
Inclusion Criteria:
Exclusion Criteria:
(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:
Exclusion Criteria:
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Informed consent
Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.
You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
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 .
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 will undergo detailed biomarker assessments. These will be compared with V122I TTR carriers and controls.
(Aim 1) Evidence of amyloid infiltration as measured by ECV
ECV expansion represents interstitial expansion from amyloid infiltration and greater levels can distinguish amyloidosis from other hypertrophic cardiomyopathies and correlate with cardiac amyloidosis disease severity.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls)
(Sub-aim 1) Δ stroke volume index (ΔSVi)
We will measure and compare ΔSVi (%) from rest to peak stress in V122I TTR carriers and non-carrier controls. Participants will exercise within the bore of the magnet using an MR compatible ergometer with adjustable electronic resistance (Ergospect Cardio-Stepper, Ergospect). Cardiac imaging will be performed at rest and during exercise at 25% (low intensity), 50% (moderate intensity), and 66% (heavy intensity) of maximal predicted work rate. Workloads will be maintained for \~5 min at each stage - 3 min to achieve a physiological steady-state and then 2 minutes for image acquisition.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls) enrolled at UT Southwestern
(Aim 1) Late gadolinium enhancement
We will use a PSIR sequence, limiting operator-dependency. Global subendocardial enhancement, transmural LGE, and focal, patchy LGE are all features of cardiac amyloidosis, representing interstitial expansion. In cardiac amyloidosis, unlike other cardiomyopathies, LGE is correlated to amyloid infiltration not interstitial fibrosis.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls)
(Aim 1) Native T1 and T2 mapping
Native T1 and T2 mapping represent diffuse interstitial expansion and myocardial edema, respectively. Native T1 measurements are abnormally elevated in amyloidosis and much higher in comparison with other cardiomyopathies that may be associated with interstitial expansion.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls)
(Aim 1) Post-gadolinium T1 signal intensity
Post-gadolinium T1 signal intensity changes characteristically with myocardial signal nulling before the blood pool signal in amyloidosis (opposite of non-amyloid hearts). We will test for this characteristic pattern using a Look-Locker "TI Scout" sequence.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls)
(Aim 1) High resolution cardiac cine imaging for cardiac morphology
High resolution cardiac cine imaging will measure cardiac morphology in all 4 chambers of the heart.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls)
(Aim 1) High resolution cardiac cine imaging for global systolic function as ejection fraction
High resolution cardiac cine imaging will measure cardiac systolic function in all 4 chambers of the heart by assessing ejection fraction.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls)
(Aim 1) High resolution cardiac cine imaging for global systolic function as fractional area change
High resolution cardiac cine imaging will measure cardiac systolic function in all 4 chambers of the heart by assessing fractional area change.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls)
(Aim 1) High resolution cardiac cine imaging for global systolic function via novel feature tracking
High resolution cardiac cine imaging will measure cardiac systolic function in all 4 chambers of the heart using novel feature tracking methods.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls)
(Aim 1) High resolution cardiac cine imaging for global diastolic function via novel feature tracking.
High resolution cardiac cine imaging will measure cardiac diastolic function in all 4 chambers of the heart using novel feature tracking methods.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls)
(Aim 1) LV strain from magnetic resonance tissue tagging
Magnetic resonance tissue tagging is the gold-standard for measuring LV strain and strain rate, providing highly sensitive measures of subclinical systolic and diastolic function.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls)
(Aim 1) Phase contrast MRI to assess diastolic function by measurement of mitral inflow velocities.
Phase contrast MRI will be used to assess LV diastolic function by assessing the ratio of early (E) and late (A) mitral inflow velocities which can be abnormal in V122I TTR carriers which can be abnormal in V122I TTR carriers.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls)
(Aim 1) Phase contrast MRI to assess diastolic function by calculating the E/e' strain rate.
Phase contrast MRI will be used to assess LV diastolic function by cine feature tracking and MR tissue tagging to calculate the E/e' strain rate which can be abnormal in V122I TTR carriers.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls)
(Sub-aim 1) End diastolic volume index (EDVi, ml/m2) in all 4 chambers
Exercise CMRI will be performed immediately following the resting CMRI protocol described for the Sub-aim 1 primary outcome.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls) enrolled at UT Southwestern
(Sub-aim 1) End systolic volume index (ESVi, ml/m2) in all 4 chambers
Exercise CMRI will be performed immediately following the resting CMRI protocol described for the Sub-aim 1 primary outcome.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls) enrolled at UT Southwestern
(Sub-aim 1) Stroke volume index (SVi, ml/m2, ΔSVi is the primary outcome) in all 4 chambers
Exercise CMRI will be performed immediately following the resting CMRI protocol described for the Sub-aim 1 primary outcome.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls) enrolled at UT Southwestern
(Sub-aim 1) Ejection fraction (LVEF, %) in all 4 chambers
Exercise CMRI will be performed immediately following the resting CMRI protocol described for the Sub-aim 1 primary outcome.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls) enrolled at UT Southwestern
(Sub-aim 1) Longitudinal strain (LS, %)
Exercise CMRI will be performed immediately following the resting CMRI protocol described for the Sub-aim 1 primary outcome.
Time frame: At baseline (for V122I TTR carriers and age-, sex-, and race-matched controls) enrolled at UT Southwestern
(Aim 2) TTR concentration
Venous blood will be collected by phlebotomy at enrollment for all participants. Both plasma and serum will be isolated and aliquoted for storage. Plasma TTR levels will be measured with commercially available ELISA assays.
Time frame: At baseline for all three cohorts
(Aim 2) RBP4 concentration
Venous blood will be collected by phlebotomy at enrollment for all participants. Both plasma and serum will be isolated and aliquoted for storage. Plasma RBP4 levels will be measured with commercially available ELISA assays.
Time frame: At baseline for all three cohorts
(Aim 2) Concentration of circulating misfolded TTR oligomers
Venous blood will be collected by phlebotomy at enrollment for all participants. Circulating misfolded TTR oligomers will be measured with peptide-based probes that selectively label these species in plasma.
Time frame: At baseline for all three cohorts
(Aim 2) TTR kinetic stability
Venous blood will be collected by phlebotomy at enrollment for all participants. TTR kinetic stability will be measured by using Western Blot techniques.
Time frame: At baseline for all three cohorts
(Sub-aim 2) Associations between each biomarker from Aim 2 and CMRI measurements from Aim 1 and Sub-aim 1
To achieve this, we will employ multivariable generalized linear mixed models to determine the independent association between these biomarkers and CMRI measurements in V122I TTR carriers without HF. Additionally, after determining the univariable association between each biomarker and outcome from Aim 1 and Sub-aim 1, we will employ a backwards selection algorithm from a list of confounders (eGFR, sex, age, hypertension, and BMI) and each biomarker to determine the biomarker(s) most closely associated with subclinical hATTR-CA.
Time frame: At baseline for all 3 cohorts and Visit 2 for V122I TTR carriers and age-, sex-, and race-matched controls
Plan to share: Undecided
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Started Nov 2022 (actual). Primary completion is estimated for Jun 2027, 55 months after the start.
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