Deze pagina is automatisch vertaald en de nauwkeurigheid van de vertaling kan niet worden gegarandeerd. Raadpleeg de Engelse versie voor een brontekst.

Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis (LICA2025)

10 augustus 2026 bijgewerkt door: 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.

Studie Overzicht

Toestand

Werving

Conditie

Gedetailleerde beschrijving

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.

Studietype

Observationeel

Inschrijving (Geschat)

70

Contacten en locaties

In dit gedeelte vindt u de contactgegevens van degenen die het onderzoek uitvoeren en informatie over waar dit onderzoek wordt uitgevoerd.

Studiecontact

Studie Locaties

  • Italië
    • Sicily
      • Messina, Sicily, Italië, 98124
        • Werving
        • AOU Policlinico G. Martino, UOC Cardiologia con UTIC
        • Contact:
        • Onderonderzoeker:
          • Roberto Licordari, MD, PhD
        • Hoofdonderzoeker:
          • Luigi Colarusso, MD, PhD Candidate

Deelname Criteria

Onderzoekers zoeken naar mensen die aan een bepaalde beschrijving voldoen, de zogenaamde geschiktheidscriteria. Enkele voorbeelden van deze criteria zijn iemands algemene gezondheidstoestand of eerdere behandelingen.

Geschiktheidscriteria

Leeftijden die in aanmerking komen voor studie

  • Volwassen
  • Oudere volwassene

Accepteert gezonde vrijwilligers

Nee

Bemonsteringsmethode

Niet-waarschijnlijkheidssteekproef

Studie Bevolking

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.

Beschrijving

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.

Studie plan

Dit gedeelte bevat details van het studieplan, inclusief hoe de studie is opgezet en wat de studie meet.

Hoe is de studie opgezet?

Ontwerpdetails

Cohorten en interventies

Groep / Cohort
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.
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.

Wat meet het onderzoek?

Primaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Liver Stiffness Measured by Transient Elastography (FibroScan)
Tijdsspanne: Baseline, 6 Months, 12 Months
Liver stiffness expressed in kilopascals (kPa) measured by transient elastography (FibroScan) in ATTR-CA patients and controls.
Baseline, 6 Months, 12 Months
Controlled Attenuation Parameter (CAP) Measured by FibroScan
Tijdsspanne: Baseline, 6 months, 12 months
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.
Baseline, 6 months, 12 months
Serum Aspartate Aminotransferase (AST/GOT)
Tijdsspanne: Baseline, 6 months, 12 months
Serum AST/GOT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
Baseline, 6 months, 12 months
Serum Alanine Aminotransferase (ALT/GPT)
Tijdsspanne: baseline, 6 months, 12 months
Serum ALT/GPT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Serum Gamma-Glutamyl Transferase (GGT)
Tijdsspanne: baseline, 6 months, 12 months
Serum gamma-glutamyl transferase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Serum Alkaline Phosphatase (ALP)
Tijdsspanne: baseline, 6 months, 12 months
Serum alkaline phosphatase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Serum Bile Acids
Tijdsspanne: baseline, 6 months, 12 months
Serum bile acid concentration (mcmol/L) measured by laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Total Bilirubin (mg/dL)
Tijdsspanne: baseline, 6 months, 12 months
Serum total bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Direct Bilirubin (mg/dL)
Tijdsspanne: baseline, 6 months, 12 months
Serum direct bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Serum Albumin (g/dL)
Tijdsspanne: baseline, 6 months, 12 months
Serum albumin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Serum Gamma Globulins (g/dL)
Tijdsspanne: baseline, 6 months, 12 months
Serum gamma-globulin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Serum Immunoglobulin M (IgM) (g/L)
Tijdsspanne: baseline, 6 months, 12 months
Serum IgM concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Serum Ferritin (ng/mL)
Tijdsspanne: baseline, 6 months, 12 months
Serum ferritin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Anti-Mitochondrial Antibodies
Tijdsspanne: baseline, 6 months, 12 months
U/ml
baseline, 6 months, 12 months
Fibrosis-4 (FIB-4) Index
Tijdsspanne: baseline, 6 months, 12 months
FIB-4 index calculated from age, AST, ALT, and platelet count, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Portal Vein Diameter Assessed by Liver Ultrasound
Tijdsspanne: baseline, 6 months, 12 months
Portal vein diameter (mm) measured by liver ultrasound, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Portal Vein Flow Velocity Assessed by Doppler Ultrasound (cm/s)
Tijdsspanne: baseline, 6 months, 12 months
Portal vein blood flow velocity measured by Doppler ultrasound, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Spleen Diameter Assessed by Ultrasound (mm)
Tijdsspanne: baseline, 6 months, 12 months
Spleen diameter measured by abdominal ultrasound, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Prothrombin Time (PT) (s)
Tijdsspanne: baseline, 6 months, 12 months
Prothrombin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Activated Partial Thromboplastin Time (aPTT) (s)
Tijdsspanne: baseline, 6 months, 12 months
Activated partial thromboplastin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
International Normalized Ratio (INR)
Tijdsspanne: baseline, 6 months, 12 months
International normalized ratio (INR) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Plasma Fibrinogen
Tijdsspanne: baseline, 6 months, 12 months
Plasma fibrinogen concentration (g/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Fibrin/Fibrinogen Degradation Products
Tijdsspanne: Baseline, 6 months, 12 months
Fibrin/fibrinogen degradation products concentration (mcg/Lm) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Baseline, 6 months, 12 months
D-Dimer
Tijdsspanne: baseline, 6 months, 12 months
D-dimer concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Alpha-2-Antiplasmin
Tijdsspanne: baseline, 6 months, 12 months
Alpha-2-antiplasmin concentration (UI/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Antithrombin
Tijdsspanne: baseline, 6 months, 12 months
Antithrombin concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Plasminogen
Tijdsspanne: baseline, 6 months, 12 months
Plasminogen concentration (IU/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Thrombin-Antithrombin Complex
Tijdsspanne: baseline, 6 months, 12 months
Plasma fibrinogen concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Plasmin-Alpha-2-Antiplasmin Complex
Tijdsspanne: baseline, 6 months, 12 months
Plasmin-Alpha-2-Antiplasmin Complex concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Prothrombin Fragment 1+2
Tijdsspanne: baseline, 6 months, 12 months
Prothrombin Fragment 1+2 concentration (pmol/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Coagulation Factor X
Tijdsspanne: baseline, 6 months, 12 months
Coagulation Factor X concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
von Willebrand Factor Antigen
Tijdsspanne: baseline, 6 months, 12 months
von Willebrand Factor Antigen concentration (IU/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months
Plasminogen Activator Inhibitor-1 (PAI-1)
Tijdsspanne: baseline, 6 months, 12 months
Plasminogen Activator Inhibitor-1 concentration (U/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
baseline, 6 months, 12 months

Secundaire uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Correlation Between Liver Stiffness (kPa) and NT-proBNP (ng/L)
Tijdsspanne: Baseline
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.
Baseline
Correlation Between Liver Stiffness and Interventricular Septal Thickness (mm)
Tijdsspanne: Baseline
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.
Baseline
Correlation Between Liver Stiffness (kPa) and Left Ventricular Global Longitudinal Strain (GLS %)
Tijdsspanne: Baseline
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.
Baseline
Correlation Between Prothrombin Fragment 1+2 (pmol/L) and NT-proBNP (ng/L)
Tijdsspanne: Baseline
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.
Baseline
Change in Liver Stiffness During Disease-Modifying Treatment
Tijdsspanne: Baseline, 6±1 months, and 12±1 months
Change in liver stiffness measured by FibroScan and expressed in kPa from baseline to 6±1 months and 12±1 months after treatment initiation.
Baseline, 6±1 months, and 12±1 months
Change in Controlled Attenuation Parameter During Disease-Modifying Treatment
Tijdsspanne: Baseline, 6±1 months, and 12±1 months
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.
Baseline, 6±1 months, and 12±1 months

Andere uitkomstmaten

Uitkomstmaat
Maatregel Beschrijving
Tijdsspanne
Correlation Between Liver Stiffness and Prothrombin Fragment 1+2
Tijdsspanne: Baseline
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.
Baseline
Correlation Between FIB-4 Index and Prothrombin Fragment 1+2
Tijdsspanne: Baseline
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.
Baseline
Correlation Between Liver Stiffness and Fibrinogen
Tijdsspanne: Baseline
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.
Baseline

Medewerkers en onderzoekers

Hier vindt u mensen en organisaties die betrokken zijn bij dit onderzoek.

Sponsor

University of Messina

Medewerkers

Azienda Ospedaliera Universitaria Policlinico "G. Martino"

Onderzoekers

  • Studie stoel: Gianluca Di Bella, MD, PhD, University of Messina and AOU Policlinico G. Martino
  • Hoofdonderzoeker: Luigi Colarusso, MD, PhD Candidate, AOU Policlinico G. Martino

Studie record data

Deze datums volgen de voortgang van het onderzoeksdossier en de samenvatting van de ingediende resultaten bij ClinicalTrials.gov. Studieverslagen en gerapporteerde resultaten worden beoordeeld door de National Library of Medicine (NLM) om er zeker van te zijn dat ze voldoen aan specifieke kwaliteitscontrolenormen voordat ze op de openbare website worden geplaatst.

Bestudeer belangrijke data

Studie start (Werkelijk)

30 januari 2026

Primaire voltooiing (Geschat)

1 januari 2028

Studie voltooiing (Geschat)

1 januari 2028

Studieregistratiedata

Eerst ingediend

12 juni 2026

Eerst ingediend dat voldeed aan de QC-criteria

10 augustus 2026

Eerst geplaatst (Werkelijk)

14 augustus 2026

Updates van studierecords

Laatste update geplaatst (Werkelijk)

14 augustus 2026

Laatste update ingediend die voldeed aan QC-criteria

10 augustus 2026

Laatst geverifieerd

1 juni 2026

Meer informatie

Termen gerelateerd aan deze studie

Trefwoorden

Aanvullende relevante MeSH-voorwaarden

Andere studie-ID-nummers

  • CEL Messina Prot. 28-25
  • Delibera n. 63/2026 (Andere identificatie: AOU Policlinico G. Martino)

Plan Individuele Deelnemersgegevens (IPD)

Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?

ONBESLIST

Beschrijving IPD-plan

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.

Informatie over medicijnen en apparaten, studiedocumenten

Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel

Nee

Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct

Nee

Deze informatie is zonder wijzigingen rechtstreeks van de website clinicaltrials.gov gehaald. Als u verzoeken heeft om uw onderzoeksgegevens te wijzigen, te verwijderen of bij te werken, neem dan contact op met register@clinicaltrials.gov. Zodra er een wijziging wordt doorgevoerd op clinicaltrials.gov, wordt deze ook automatisch bijgewerkt op onze website .

Abonneren