Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis (LICA2025)
10. srpna 2026 aktualizováno: Gianluca Di Bella, University of Messina
Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis (ATTR-CA): New Horizons in Disease Staging and Follow-Up
Transthyretin cardiac amyloidosis (ATTR-CA) is a progressive infiltrative cardiomyopathy caused by the deposition of misfolded transthyretin protein within the myocardium. Current disease staging and follow-up strategies mainly rely on cardiac biomarkers and renal function; however, the systemic nature of ATTR suggests that additional organ involvement may provide valuable prognostic information.
The purpose of this prospective observational study is to investigate liver dysfunction and coagulation abnormalities in patients with wild-type or hereditary ATTR-CA and to evaluate their potential role as novel markers of disease severity and progression. Patients with ATTR-CA will be compared with an age-matched control population with non-amyloid hypertrophic cardiomyopathy.
Clinical, laboratory, echocardiographic, hepatic ultrasound, liver stiffness, and coagulation parameters will be assessed at baseline and during follow-up. The study will also evaluate changes in these parameters after 6 and 12 months of treatment with tafamidis.
The results may improve the understanding of cardio-hepatic interactions in ATTR-CA and identify new tools for disease staging and longitudinal monitoring.
Přehled studie
Postavení
Nábor
Detailní popis
Transthyretin cardiac amyloidosis (ATTR-CA) is an increasingly recognized cause of heart failure and left ventricular hypertrophy in older adults. Although several prognostic models have been developed for ATTR-CA, most currently available staging systems are based primarily on cardiac biomarkers and renal function. These approaches may not fully capture the systemic nature of the disease.
Emerging evidence suggests that liver dysfunction and coagulation abnormalities may represent underexplored manifestations of ATTR-CA. Liver involvement may result from direct amyloid deposition, chronic venous congestion related to heart failure, or a combination of both mechanisms. Similarly, alterations in coagulation pathways may reflect hepatic dysfunction and systemic disease burden.
LICA2025 is a single-center, prospective, observational study designed to evaluate biochemical and instrumental markers of liver function and coagulation in patients with wild-type or hereditary ATTR-CA followed at the University Hospital G. Martino of Messina, Italy. A control population with non-amyloid hypertrophic cardiomyopathy will be enrolled for comparison.
The primary objective is to compare liver and coagulation parameters between ATTR-CA patients and controls. Secondary objectives include evaluating the relationship between hepatic/coagulation abnormalities and cardiac disease severity, assessing changes after 6±1 and 12±1 months of tafamidis therapy, and exploring potential interactions between liver dysfunction and coagulation disturbances.
Participants will undergo clinical evaluation, laboratory testing, electrocardiography, transthoracic echocardiography, hepatic ultrasound, liver elastography (FibroScan), and coagulation assessment according to the study protocol. Follow-up evaluations will be performed at baseline, 6 months, and 12 months.
The study aims to identify novel biomarkers and imaging parameters that may improve disease staging, risk stratification, and longitudinal monitoring in transthyretin cardiac amyloidosis.
Typ studie
Pozorovací
Zápis (Odhadovaný)
70
Kontakty a umístění
Tato část poskytuje kontaktní údaje pro ty, kteří studii provádějí, a informace o tom, kde se tato studie provádí.
Studijní kontakt
- Jméno: Luigi Colarusso, MD, PhD Candidate
- Telefonní číslo: +390902212341
- E-mail: luigi.colarusso@polime.it
Studijní místa
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Sicily
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Messina, Sicily, Itálie, 98124
- Nábor
- AOU Policlinico G. Martino, UOC Cardiologia con UTIC
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Kontakt:
- Luigi Colarusso, MD, PhD Candidate
- Telefonní číslo: +390902212341
- E-mail: luigi.colarusso@polime.it
-
Dílčí vyšetřovatel:
- Roberto Licordari, MD, PhD
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Vrchní vyšetřovatel:
- Luigi Colarusso, MD, PhD Candidate
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Kritéria účasti
Výzkumníci hledají lidi, kteří odpovídají určitému popisu, kterému se říká kritéria způsobilosti. Některé příklady těchto kritérií jsou celkový zdravotní stav osoby nebo předchozí léčba.
Kritéria způsobilosti
Věk způsobilý ke studiu
- Dospělý
- Starší dospělý
Přijímá zdravé dobrovolníky
Ne
Metoda odběru vzorků
Vzorek nepravděpodobnosti
Studijní populace
Adult patients with wild-type or hereditary transthyretin cardiac amyloidosis (ATTR-CA) followed at the University Hospital G. Martino, Messina, Italy, and an age-matched control population with non-amyloid hypertrophic phenotype cardiomyopathy.
Popis
Inclusion Criteria:
- Written informed consent obtained prior to study participation.
- Diagnosis of wild-type or hereditary transthyretin cardiac amyloidosis (ATTR-CA) according to current European recommendations.
- Ability to comply with study procedures and follow-up visits.
Exclusion Criteria:
- Age younger than 18 years.
- Severe liver dysfunction due to causes other than amyloidosis.
- Inability to comply with study procedures because of language barriers, cognitive impairment, or severe psychiatric disorders.
- Comorbidities associated with life expectancy less than 12 months.
- Active alcohol or substance abuse.
- For coagulation analyses: congenital coagulation disorders, thrombotic disorders, active malignancy, or sepsis.
- Pregnancy or breastfeeding.
Studijní plán
Tato část poskytuje podrobnosti o studijním plánu, včetně toho, jak je studie navržena a co studie měří.
Jak je studie koncipována?
Detaily designu
Kohorty a intervence
Skupina / kohorta |
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ATTR-CA Patients
Patients with wild-type or hereditary transthyretin cardiac amyloidosis (ATTR-CA) diagnosed according to current European recommendations and followed at the University Hospital G. Martino, Messina.
Participants will undergo clinical, laboratory, echocardiographic, hepatic ultrasound, liver elastography, and coagulation assessments at baseline and during follow-up.
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Hypertrophic Phenotype Controls
Age-matched patients with non-amyloid hypertrophic phenotype cardiomyopathy serving as a control population.
Participants will undergo the same clinical, laboratory, echocardiographic, hepatic, and coagulation evaluations as the ATTR-CA group.
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Co je měření studie?
Primární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
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Liver Stiffness Measured by Transient Elastography (FibroScan)
Časové okno: Baseline, 6 Months, 12 Months
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Liver stiffness expressed in kilopascals (kPa) measured by transient elastography (FibroScan) in ATTR-CA patients and controls.
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Baseline, 6 Months, 12 Months
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Controlled Attenuation Parameter (CAP) Measured by FibroScan
Časové okno: Baseline, 6 months, 12 months
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Controlled attenuation parameter (CAP) measured by FibroScan as an instrumental measure of hepatic steatosis, expressed in decibels per meter (dB/m), compared between patients with ATTR-CA and controls.
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Baseline, 6 months, 12 months
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Serum Aspartate Aminotransferase (AST/GOT)
Časové okno: Baseline, 6 months, 12 months
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Serum AST/GOT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
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Baseline, 6 months, 12 months
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Serum Alanine Aminotransferase (ALT/GPT)
Časové okno: baseline, 6 months, 12 months
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Serum ALT/GPT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Gamma-Glutamyl Transferase (GGT)
Časové okno: baseline, 6 months, 12 months
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Serum gamma-glutamyl transferase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Alkaline Phosphatase (ALP)
Časové okno: baseline, 6 months, 12 months
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Serum alkaline phosphatase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Bile Acids
Časové okno: baseline, 6 months, 12 months
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Serum bile acid concentration (mcmol/L) measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Total Bilirubin (mg/dL)
Časové okno: baseline, 6 months, 12 months
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Serum total bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Direct Bilirubin (mg/dL)
Časové okno: baseline, 6 months, 12 months
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Serum direct bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Albumin (g/dL)
Časové okno: baseline, 6 months, 12 months
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Serum albumin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Gamma Globulins (g/dL)
Časové okno: baseline, 6 months, 12 months
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Serum gamma-globulin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Immunoglobulin M (IgM) (g/L)
Časové okno: baseline, 6 months, 12 months
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Serum IgM concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Serum Ferritin (ng/mL)
Časové okno: baseline, 6 months, 12 months
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Serum ferritin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Anti-Mitochondrial Antibodies
Časové okno: baseline, 6 months, 12 months
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U/ml
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baseline, 6 months, 12 months
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Fibrosis-4 (FIB-4) Index
Časové okno: baseline, 6 months, 12 months
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FIB-4 index calculated from age, AST, ALT, and platelet count, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Portal Vein Diameter Assessed by Liver Ultrasound
Časové okno: baseline, 6 months, 12 months
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Portal vein diameter (mm) measured by liver ultrasound, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Portal Vein Flow Velocity Assessed by Doppler Ultrasound (cm/s)
Časové okno: baseline, 6 months, 12 months
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Portal vein blood flow velocity measured by Doppler ultrasound, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Spleen Diameter Assessed by Ultrasound (mm)
Časové okno: baseline, 6 months, 12 months
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Spleen diameter measured by abdominal ultrasound, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Prothrombin Time (PT) (s)
Časové okno: baseline, 6 months, 12 months
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Prothrombin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Activated Partial Thromboplastin Time (aPTT) (s)
Časové okno: baseline, 6 months, 12 months
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Activated partial thromboplastin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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International Normalized Ratio (INR)
Časové okno: baseline, 6 months, 12 months
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International normalized ratio (INR) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Plasma Fibrinogen
Časové okno: baseline, 6 months, 12 months
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Plasma fibrinogen concentration (g/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Fibrin/Fibrinogen Degradation Products
Časové okno: Baseline, 6 months, 12 months
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Fibrin/fibrinogen degradation products concentration (mcg/Lm) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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Baseline, 6 months, 12 months
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D-Dimer
Časové okno: baseline, 6 months, 12 months
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D-dimer concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Alpha-2-Antiplasmin
Časové okno: baseline, 6 months, 12 months
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Alpha-2-antiplasmin concentration (UI/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Antithrombin
Časové okno: baseline, 6 months, 12 months
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Antithrombin concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Plasminogen
Časové okno: baseline, 6 months, 12 months
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Plasminogen concentration (IU/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Thrombin-Antithrombin Complex
Časové okno: baseline, 6 months, 12 months
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Plasma fibrinogen concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Plasmin-Alpha-2-Antiplasmin Complex
Časové okno: baseline, 6 months, 12 months
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Plasmin-Alpha-2-Antiplasmin Complex concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Prothrombin Fragment 1+2
Časové okno: baseline, 6 months, 12 months
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Prothrombin Fragment 1+2 concentration (pmol/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Coagulation Factor X
Časové okno: baseline, 6 months, 12 months
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Coagulation Factor X concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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von Willebrand Factor Antigen
Časové okno: baseline, 6 months, 12 months
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von Willebrand Factor Antigen concentration (IU/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Plasminogen Activator Inhibitor-1 (PAI-1)
Časové okno: baseline, 6 months, 12 months
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Plasminogen Activator Inhibitor-1 concentration (U/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
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baseline, 6 months, 12 months
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Sekundární výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Correlation Between Liver Stiffness (kPa) and NT-proBNP (ng/L)
Časové okno: Baseline
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Correlation between liver stiffness measured by FibroScan (kPa) and plasma NT-proBNP concentration (ng/L) in patients with ATTR-CA.
Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
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Baseline
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Correlation Between Liver Stiffness and Interventricular Septal Thickness (mm)
Časové okno: Baseline
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Correlation between liver stiffness measured by FibroScan (kPa) and interventricular septal thickness expressed in mm measured by transthoracic echocardiography in patients with ATTR-CA.
Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
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Baseline
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Correlation Between Liver Stiffness (kPa) and Left Ventricular Global Longitudinal Strain (GLS %)
Časové okno: Baseline
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Correlation between liver stiffness measured by FibroScan (kPa) and Global Longitudinal Strain (expressed in %) measured by transthoracic echocardiography in patients with ATTR-CA.
Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
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Baseline
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Correlation Between Prothrombin Fragment 1+2 (pmol/L) and NT-proBNP (ng/L)
Časové okno: Baseline
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Correlation between Prothrombin Fragment 1+2 (pmol/L) and NT-proBNP (ng/L) measured by standard laboratory testing in patients with ATTR-CA.
Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
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Baseline
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Change in Liver Stiffness During Disease-Modifying Treatment
Časové okno: Baseline, 6±1 months, and 12±1 months
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Change in liver stiffness measured by FibroScan and expressed in kPa from baseline to 6±1 months and 12±1 months after treatment initiation.
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Baseline, 6±1 months, and 12±1 months
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Change in Controlled Attenuation Parameter During Disease-Modifying Treatment
Časové okno: Baseline, 6±1 months, and 12±1 months
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Change in controlled attenuation parameter (CAP) measured by FibroScan and expressed in dB/m from baseline to 6±1 months and 12±1 months after treatment initiation.
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Baseline, 6±1 months, and 12±1 months
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Další výstupní opatření
Měření výsledku |
Popis opatření |
Časové okno |
|---|---|---|
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Correlation Between Liver Stiffness and Prothrombin Fragment 1+2
Časové okno: Baseline
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Correlation between liver stiffness measured by transient elastography (FibroScan), expressed in kPa, and plasma prothrombin fragment 1+2 concentration in patients with ATTR-CA.
Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
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Baseline
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Correlation Between FIB-4 Index and Prothrombin Fragment 1+2
Časové okno: Baseline
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Correlation between FIB-4 and plasma prothrombin fragment 1+2 concentration in patients with ATTR-CA.
Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
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Baseline
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Correlation Between Liver Stiffness and Fibrinogen
Časové okno: Baseline
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Correlation between liver stiffness measured by transient elastography (FibroScan), expressed in kPa, and plasma fibrinogen concentration in patients with ATTR-CA.
Correlation will be assessed using Pearson or Spearman correlation coefficient, as appropriate.
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Baseline
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Spolupracovníci a vyšetřovatelé
Zde najdete lidi a organizace zapojené do této studie.
Sponzor
Spolupracovníci
Vyšetřovatelé
- Studijní židle: Gianluca Di Bella, MD, PhD, University of Messina and AOU Policlinico G. Martino
- Vrchní vyšetřovatel: Luigi Colarusso, MD, PhD Candidate, AOU Policlinico G. Martino
Termíny studijních záznamů
Tato data sledují průběh záznamů studie a předkládání souhrnných výsledků na ClinicalTrials.gov. Záznamy ze studií a hlášené výsledky jsou před zveřejněním na veřejné webové stránce přezkoumány Národní lékařskou knihovnou (NLM), aby se ujistily, že splňují specifické standardy kontroly kvality.
Hlavní termíny studia
Začátek studia (Aktuální)
30. ledna 2026
Primární dokončení (Odhadovaný)
1. ledna 2028
Dokončení studie (Odhadovaný)
1. ledna 2028
Termíny zápisu do studia
První předloženo
12. června 2026
První předloženo, které splnilo kritéria kontroly kvality
10. srpna 2026
První zveřejněno (Aktuální)
14. srpna 2026
Aktualizace studijních záznamů
Poslední zveřejněná aktualizace (Aktuální)
14. srpna 2026
Odeslaná poslední aktualizace, která splnila kritéria kontroly kvality
10. srpna 2026
Naposledy ověřeno
1. června 2026
Více informací
Termíny související s touto studií
Klíčová slova
Další relevantní podmínky MeSH
- Nemoci nervového systému
- Cévní onemocnění
- Kardiovaskulární choroby
- Srdeční choroba
- Neuromuskulární onemocnění
- Metabolismus, vrozené chyby
- Genetické choroby, vrozené
- Metabolické choroby
- Onemocnění periferního nervového systému
- Nemoci trávicího systému
- Hematologická onemocnění
- Neurodegenerativní onemocnění
- Heredodegenerativní poruchy, nervový systém
- Hemoragické poruchy
- Nedostatky proteostázy
- Amyloidní neuropatie
- Amyloidóza, familiární
- Amyloidóza
- Vrozené, dědičné a neonatální nemoci a abnormality
- Nutriční a metabolické nemoci
- Hemická a lymfatická onemocnění
- Srdeční selhání
- Onemocnění jater
- Kardiomyopatie
- Hemostatické poruchy
- Amyloidní neuropatie, familiární
- Amyloidóza, dědičná, související s transthyretinem
Další identifikační čísla studie
- CEL Messina Prot. 28-25
- Delibera n. 63/2026 (Jiný identifikátor: AOU Policlinico G. Martino)
Plán pro data jednotlivých účastníků (IPD)
Plánujete sdílet data jednotlivých účastníků (IPD)?
NEROZHODNÝ
Popis plánu IPD
The decision regarding IPD sharing has not yet been finalized.
Any future data sharing will be considered in accordance with applicable ethical approvals, participant consent, institutional policies, and data protection regulations.
Informace o lécích a zařízeních, studijní dokumenty
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Ne
Studuje produkt zařízení regulovaný americkým úřadem FDA
Ne
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