Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis (LICA2025)
maanantai 10. elokuuta 2026 päivittänyt: 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.
Tutkimuksen yleiskatsaus
Tila
Rekrytointi
Yksityiskohtainen kuvaus
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.
Opintotyyppi
Havainnollistava
Ilmoittautuminen (Arvioitu)
70
Yhteystiedot ja paikat
Tässä osiossa on tutkimuksen suorittajien yhteystiedot ja tiedot siitä, missä tämä tutkimus suoritetaan.
Opiskeluyhteys
- Nimi: Luigi Colarusso, MD, PhD Candidate
- Puhelinnumero: +390902212341
- Sähköposti: luigi.colarusso@polime.it
Opiskelupaikat
-
-
Sicily
-
Messina, Sicily, Italia, 98124
- Rekrytointi
- AOU Policlinico G. Martino, UOC Cardiologia con UTIC
-
Ottaa yhteyttä:
- Luigi Colarusso, MD, PhD Candidate
- Puhelinnumero: +390902212341
- Sähköposti: luigi.colarusso@polime.it
-
Alatutkija:
- Roberto Licordari, MD, PhD
-
Päätutkija:
- Luigi Colarusso, MD, PhD Candidate
-
-
Osallistumiskriteerit
Tutkijat etsivät ihmisiä, jotka sopivat tiettyyn kuvaukseen, jota kutsutaan kelpoisuuskriteereiksi. Joitakin esimerkkejä näistä kriteereistä ovat henkilön yleinen terveydentila tai aiemmat hoidot.
Kelpoisuusvaatimukset
Opintokelpoiset iät
- Aikuinen
- Vanhempi Aikuinen
Hyväksyy terveitä vapaaehtoisia
Ei
Näytteenottomenetelmä
Ei-todennäköisyysnäyte
Tutkimusväestö
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.
Kuvaus
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.
Opintosuunnitelma
Tässä osiossa on tietoja tutkimussuunnitelmasta, mukaan lukien kuinka tutkimus on suunniteltu ja mitä tutkimuksella mitataan.
Miten tutkimus on suunniteltu?
Suunnittelun yksityiskohdat
Kohortit ja interventiot
Ryhmä/Kohortti |
|---|
|
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.
|
Mitä tutkimuksessa mitataan?
Ensisijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Liver Stiffness Measured by Transient Elastography (FibroScan)
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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
Aikaikkuna: baseline, 6 months, 12 months
|
U/ml
|
baseline, 6 months, 12 months
|
|
Fibrosis-4 (FIB-4) Index
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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)
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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)
Aikaikkuna: 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
|
Toissijaiset tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Correlation Between Liver Stiffness (kPa) and NT-proBNP (ng/L)
Aikaikkuna: 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)
Aikaikkuna: 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 %)
Aikaikkuna: 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)
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
|
Muut tulostoimenpiteet
Tulosmittaus |
Toimenpiteen kuvaus |
Aikaikkuna |
|---|---|---|
|
Correlation Between Liver Stiffness and Prothrombin Fragment 1+2
Aikaikkuna: 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
Aikaikkuna: 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
Aikaikkuna: 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
|
Yhteistyökumppanit ja tutkijat
Täältä löydät tähän tutkimukseen osallistuvat ihmiset ja organisaatiot.
Sponsori
Yhteistyökumppanit
Tutkijat
- Opintojen puheenjohtaja: Gianluca Di Bella, MD, PhD, University of Messina and AOU Policlinico G. Martino
- Päätutkija: Luigi Colarusso, MD, PhD Candidate, AOU Policlinico G. Martino
Opintojen ennätyspäivät
Nämä päivämäärät seuraavat ClinicalTrials.gov-sivustolle lähetettyjen tutkimustietueiden ja yhteenvetojen edistymistä. National Library of Medicine (NLM) tarkistaa tutkimustiedot ja raportoidut tulokset varmistaakseen, että ne täyttävät tietyt laadunvalvontastandardit, ennen kuin ne julkaistaan julkisella verkkosivustolla.
Opi tärkeimmät päivämäärät
Opiskelun aloitus (Todellinen)
Perjantai 30. tammikuuta 2026
Ensisijainen valmistuminen (Arvioitu)
Lauantai 1. tammikuuta 2028
Opintojen valmistuminen (Arvioitu)
Lauantai 1. tammikuuta 2028
Opintoihin ilmoittautumispäivät
Ensimmäinen lähetetty
Perjantai 12. kesäkuuta 2026
Ensimmäinen toimitettu, joka täytti QC-kriteerit
Maanantai 10. elokuuta 2026
Ensimmäinen Lähetetty (Todellinen)
Perjantai 14. elokuuta 2026
Tutkimustietojen päivitykset
Viimeisin päivitys julkaistu (Todellinen)
Perjantai 14. elokuuta 2026
Viimeisin lähetetty päivitys, joka täytti QC-kriteerit
Maanantai 10. elokuuta 2026
Viimeksi vahvistettu
Maanantai 1. kesäkuuta 2026
Lisää tietoa
Tähän tutkimukseen liittyvät termit
Avainsanat
- Sydämen vajaatoiminta
- Hemostaasi
- Biomarkkerit
- Ekokardiografia
- Maksan toimintahäiriö
- ATTR
- Fibroscan
- Transtyretiini-amyloidoosi
- Sydämen amyloidoosi
- Tafamidis
- Maksan jäykkyys
- Acoramidis
- Koagulaatiohäiriö
- Sairauden vaiheistus
- ATTR-CA
- Hepatic Congestion
- Cardiohepatic Syndrome
- Wild-Type ATTR
- Hereditary ATTR
Muita asiaankuuluvia MeSH-ehtoja
- Hermoston sairaudet
- Verisuonisairaudet
- Sydän-ja verisuonitaudit
- Sydänsairaudet
- Neuromuskulaariset sairaudet
- Aineenvaihdunta, synnynnäiset virheet
- Geneettiset sairaudet, synnynnäiset
- Metaboliset sairaudet
- Ääreishermoston sairaudet
- Ruoansulatuskanavan sairaudet
- Hematologiset sairaudet
- Neurodegeneratiiviset sairaudet
- Heredodegeneratiiviset häiriöt, hermosto
- Hemorragiset häiriöt
- Proteostaasin puutteet
- Amyloidin neuropatiat
- Amyloidoosi, perhe
- Amyloidoosi
- Synnynnäiset, perinnölliset ja vastasyntyneiden sairaudet ja poikkeavuudet
- Ravitsemukselliset ja aineenvaihduntataudit
- Hemic- ja imusuutteet
- Sydämen vajaatoiminta
- Maksasairaudet
- Kardiomyopatiat
- Hemostaattiset häiriöt
- Amyloidinen neuropatia, perhe
- Amyloidoosi, perinnöllinen, transtyretiiniin liittyvä
Muut tutkimustunnusnumerot
- CEL Messina Prot. 28-25
- Delibera n. 63/2026 (Muu tunniste: AOU Policlinico G. Martino)
Yksittäisten osallistujien tietojen suunnitelma (IPD)
Aiotko jakaa yksittäisten osallistujien tietoja (IPD)?
PÄÄTTÄMÄTÖN
IPD-suunnitelman kuvaus
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.
Lääke- ja laitetiedot, tutkimusasiakirjat
Tutkii yhdysvaltalaista FDA sääntelemää lääkevalmistetta
Ei
Tutkii yhdysvaltalaista FDA sääntelemää laitetuotetta
Ei
Nämä tiedot haettiin suoraan verkkosivustolta clinicaltrials.gov ilman muutoksia. Jos sinulla on pyyntöjä muuttaa, poistaa tai päivittää tutkimustietojasi, ota yhteyttä register@clinicaltrials.gov. Heti kun muutos on otettu käyttöön osoitteessa clinicaltrials.gov, se päivitetään automaattisesti myös verkkosivustollemme .