Clinical Research Directory

The Eplontersen Pregnancy and Lactation Outcomes Study

The overall objective of this DPSS is to describe the occurrence of pregnancy and maternal complications, adverse effects on the developing fetus and neonate, and adverse effects on the infant associated with exposure to eplontersen during pregnancy and/or lactation.

Acoramidis Transthyretin Amyloidosis Prevention Trial in the Young (ACT-EARLY) Study in Asymptomatic Carriers of a Pathogenic TTR Variant

Transthyretin amyloidosis (ATTR) is a disease where the normally occurring transthyretin (TTR) protein falls apart and forms amyloid, a sticky plaque- like substance that accumulates in different organs in the body and can cause damage to the organ. There are two ways that the TTR protein can fall apart. One way occurs as a person ages, where the normal TTR protein can fall apart and form amyloid that may no longer be sufficiently cleared by the body. This type of ATTR is known as wild-type ATTR (ATTRwt). The other way occurs when a person inherits a defective TTR gene that causes the TTR protein to spontaneously fall apart. This form of the disease is known as variant ATTR (ATTRv) and can be detected in adults by a genetic test of their TTR gene before they age. Amyloid build-up in the heart causes the heart wall to become thick and stiff and can result in heart failure and even death. Accumulation of TTR amyloid in the heart is known as transthyretin amyloid cardiomyopathy or ATTR-CM. Amyloid can also deposit in the nerve tissues leading to nerve problems. Accumulation of TTR in the nerves is known as transthyretin amyloid polyneuropathy or ATTR-PN. Acoramidis is an experimental drug designed to bind tightly to TTR in the blood and stabilize its structure, so it does not form the harmful amyloid plaques that can cause damage to organs. This study is intended to determine if treatment with acoramidis in participants with ATTRv who have not yet developed any symptoms of disease can prevent or delay the development of ATTR-CM or ATTR-PN disease. If adults with an inherited defective TTR gene are treated early before any of the symptoms of disease have developed, it may be possible to delay the onset or prevent the disease entirely.

Non-interventional Study of Patients With Transthyretin (ATTR) Amyloidosis

The MaesTTRo study aims to enroll a global cohort of patients with transthyretin (ATTR) amyloidosis to longitudinally observe the natural course of the disease and describe real-world treatment patterns and outcomes. In addition, information on the effectiveness of ATTR amyloidosis treatments, including eplontersen, which is a ligand-conjugated antisense oligonucleotide gene silencing treatment targeting activity against both the mutant and wild-type TTR protein, will be collected.

ATTRACT-52: Primary Care Cardiac Amyloidosis Screening in Ordu, Turkey

Cardiac amyloidosis is a progressive infiltrative cardiomyopathy, most commonly related to transthyretin (ATTR) misfolding. Although considered rare, emerging data suggest higher prevalence in specific regions, including the Black Sea area of Turkey. Early recognition improves outcomes. ATTRACT-52 is a prospective, observational, non-interventional screening study in primary care (family medicine centers) across Ordu province. Adults ≥65 years with cardiac or musculoskeletal "red flags" will be screened; those meeting high-suspicion criteria will undergo NT-proBNP/BNP testing at the primary care level to aid risk stratification prior to referral for confirmatory diagnostics.

Spectrum of Peripheral and Autonomic Neuropathies in Patients With aTTRwt Amyloidosis and Response to Patisiran Therapy

To evaluate the efficacy and safety of patisiran in patients with wtATTR amyloidosis and symptomatic polyneuropathy by evaluating the effect on neurologic impairment and quality of life.

Myocardial Effects in Patients With ATTRv With Polyneuropathy Treated With Patisiran or Vutrisiran

ATTRv amyloidosis is a systemic disease with two clinical forms, neurological and cardiological, which are sometimes combined (so-called mixed forms). Patisiran and vutrisiran have shown protective effects on the progression of neurological damage. The effects of Patisiran or vutrisiran on the heart remain incompletely understood. The aim of this study is to better understand the morphological and functional cardiac consequences in ATTRv patients with stage 1 or 2 polyneuropathy with a mixed form treated with Patisiran or vutrisiran

Characterizing Iodine-124 Evuzumitide (AT-01) in Systemic Amyloidosis

This is a single center prospective study evaluating 124I-evuzumitide in patients with systemic amyloidosis. The purpose of this study is to 1)identify and characterize the distribution and uptake of 124I-evuzumitide in patients with transthyretin amyloid cardiomyopathy (ATTR-CM) and 2) Correlate the uptake with the structure and function of different organs, including the heart. To achieve these goals, eligible patients will undergo primarily hybrid positron emission tomography and magnetic resonance imaging (PET/MRI). In a subgroup of patients who are unable to undergo PET/MR, computed tomography will be used instead of MRI (i.e. PET/CT). In a subgroup of patients, repeat imaging with the same modality will be done at a interval of 6-12 months. Clinically available data (demographics, phenotype, imaging, laboratory) will also be collected to characterize the disease in each patient.

Phenotyping and Characterization of wtATTR-CM (TRACE 1)

Descriptive cross-sectional study on 100 consecutive ATTRwt-CM patients reflecting all NAC stages aiming primarily to investigate ATTRwt-CM patient's quality of life (QoL) measures and their relation to ATTRwt-CM severity. Secondarily aiming to investigate the possibility to measure misTTR and fragTTR in plasma and urine and to detect fragTTR in endomyocardial biopsies from ATTRwt-CM patients. To investigate whether misTTR and fragTTR levels are correlated with ATTRwt-CM severity.

Retrospective Identification of Scintigraphic Cardiac Amyloidosis (RISCA)

This study aims to determine the positive predictive value of incidental cardiac uptake on bone scintigraphy for diagnosing transthyretin cardiac amyloidosis, in patients who underwent scintigraphy for reasons other than suspected amyloidosis. The study is an observational, descriptive, multicenter, national study using retrospective data from routine care. Patients with incidental cardiac uptake will be recalled for further diagnostic assessment.

Prevalence and Prediction of ATTR in Ambulatory Patients With HFpEF

Recent studies have shown that transthyretin amyloidosis (ATTR) can sometimes cause a type of heart failure where the pumping function of the heart is normal, also known as Heart Failure with Preserved Ejection Fraction (HFpEF) or diastolic heart failure. In this single center diagnostic study, we will evaluate for ATTR in patients with HFpEF in order to to determine how frequently this occurs and how we can predict which heart failure patients may have TTR amyloidosis. Our goal is to identify amyloidosis in heart failure patients earlier so that they can start treatment.

PL_GNT01_ISR_Grant 53234273

We carry out a prospective non-interventional, longitudinal, observational multicentre registry designed to improve our understanding of the epidemiology of TTR amyloidosis in our country. The main objective of the proposed study is to determine the occurrence of TTR amyloidosis and describe clinical profile of patients in the population of our country.

New Biomarkers and Plasma Prothrombotic Potential in Cardiac Transthyretin Amyloidosis

The development of cardiac amyloidosis is caused by the deposition of misfolded, insoluble proteins in the extracellular matrix of tissues. An important element of the clinical picture of the disease is the increased risk of thromboembolic complications, independent of the occurrence of atrial fibrillation, and the presence of intracardiac thrombi. The pathomechanism may be related to an increase in filling pressure or amyloid infiltration leading to myocardial damage and endothelial dysfunction, which may activate the prothrombotic inflammatory cascade, resulting in increased thrombogenic potential. Currently, there is limited published data on the potential role of new heart failure biomarkers in the assessment of ATTR cardiomyopathy, particularly in the assessment of asymptomatic carriers of pathogenic TTR variants. Moreover, there are few literature reports on the direct assessment of the coagulation system in this group of patients, and the pathomechanism of the increased thromboembolic risk is unexplored. Purpose of the study: To assess the diagnostic value of biomarkers related to heart failure (growth differentiation factor-15 (GDF15), soluble suppression of tumorigenicity-2 (ST2), galectin-3), amyloidosis ( TTR, tissue inhibitor of metalloproteinase-1 (TIMP-1), matrix metalloproteinase-9 (MMP-9, matrix metalloproteinase-9), neurofilament light chain (NfL)) and the generation potential thrombin as a marker of the prothrombotic state in the course of ATTR. Methods: This prospective, single-center study will include consecutive patients diagnosed with ATTR cardiomyopathy (GROUP 1, n=30), asymptomatic carriers of pathogenic TTR variants (GROUP 2, n=30), and a matched control group of healthy volunteers (GROUP 3 , n=20). Material for research was collected and secured from all study participants. After giving informed consent, all patients will be tested using the ELISA method from peripheral blood (enzyme-linked immunosorbent assay) GDF15, ST2, TTR, TIMP-1, MMP-9, galectin-3, NfL. The values of these biomarkers will be compared in subgroups and correlated with clinical data, laboratory test results, echocardiography including analysis of left ventricular global strain (GLS), and scintigraphy. Additionally, the prothrombotic potential of plasma will be tested in both groups of patients using the calibrated automatic thrombogram (CAT) method, in accordance with the protocol previously used in the laboratory Expected results: The project will provide information on the value of biomarkers in the assessment of ATTR cardiomyopathy, especially in the assessment of asymptomatic carriers of pathogenic TTR variants, which may translate into the creation of a diagnostic algorithm for early identification of the development of the disease. Moreover, it will allow us to determine whether patients with cardiac ATTR are characterized by a prothrombotic state, which has not yet been described in the literature and may have potential clinical implications.