Subclinical Transthyretin Cardiac Amyloidosis in V122I TTR Carriers

Launched by UNIVERSITY OF TEXAS SOUTHWESTERN MEDICAL CENTER · Aug 3, 2022

Keywords

ClinConnect Summary

This clinical trial is studying a condition called hereditary transthyretin amyloidosis (hATTR-CA), which can cause serious heart problems. The researchers are particularly focused on individuals who carry a specific genetic change known as V122I, which is common among Black individuals. The goal is to find out if there are early signs (called subclinical) of this heart disease in these carriers before they develop severe symptoms, and to identify specific markers in the blood that could indicate how the disease is progressing.

To participate in this trial, individuals must be between the ages of 30 and 80 and carry the V122I gene change, but they should not have any history of heart failure. Participants will undergo special heart imaging and blood tests to help researchers learn more about the condition and its early signs. This study is important because it aims to improve early detection and treatment options for those at risk of heart problems related to hATTR-CA. If you or a family member are interested and meet the eligibility criteria, this trial could provide valuable insights into managing this condition.

Gender

ALL

Eligibility 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