Investigating early signs of heart disease in specific genetic carriers
Identifying Subclinical Transthyretin Cardiac Amyloidosis in Asymptomatic Carriers of the V122I TTR Allele
This study is trying to find early signs of heart disease in people with a specific genetic mutation linked to a heart condition called amyloidosis to help catch the disease sooner.
Quick facts
| Study type | Observational |
|---|---|
| Enrollment | 500 (estimated) |
| Ages | 30 Years to 80 Years |
| Sex | All |
| Sponsor | University of Texas Southwestern Medical Center Academic / other |
| Locations | 3 sites (New York, New York and 2 other locations) |
| Trial ID | NCT05489549 on ClinicalTrials.gov |
What this trial studies
This observational study focuses on individuals who are carriers of the V122I transthyretin (TTR) mutation, which is linked to hereditary cardiac amyloidosis. The study aims to identify the presence of subclinical heart disease and potential biomarkers that indicate the progression of amyloidosis in these carriers. By utilizing advanced imaging techniques and biomarker analysis, the research seeks to detect early stages of the disease, which is often diagnosed too late for effective treatment. The findings could lead to improved early diagnosis and management strategies for affected individuals.
Who should consider this trial
Good fit: Ideal candidates for this study are men and women aged 30-80 who are V122I TTR carriers or matched non-carriers without a history of heart failure.
Not a fit: Patients with a self-reported history of heart failure or other known causes of cardiomyopathy may not benefit from this study.
Why it matters
Potential benefit: If successful, this study could lead to earlier detection and intervention for patients at risk of hereditary cardiac amyloidosis, potentially improving their outcomes.
How similar studies have performed: While this approach is focused on a specific genetic mutation, similar studies have shown promise in early detection of cardiac amyloidosis, suggesting potential for success.
Eligibility criteria
Show full inclusion / exclusion criteria
(V122I TTR carriers (or matched non-carriers))
Inclusion Criteria:
* Men and women ages 30-80 who are V122I TTR carriers (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 V122I hATTR-CA, we will enroll probands with HF from Aim 1 or patients with suspected symptomatic V122I hATTR-CA from the three study sites.)
Inclusion Criteria:
* Men and women ages 30-80 who have symptomatic V122I 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 V122I 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
Where this trial is running
New York, New York and 2 other locations
- Columbia University Medical Center — New York, New York, United States (Recruiting)
- Cleveland Clinic — Cleveland, Ohio, United States (Recruiting)
- University of Texas Southwestern Medical Center — Dallas, Texas, United States (Recruiting)
Study contacts
- Principal investigator: Justin L Grodin, MD MPH — UT Southwestern
- Study coordinator: Amy Browning
- Email: Amy.Browning@utsouthwestern.edu
- Phone: 214-645-8040
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.