Transthyretin (TTR) Amyloid CardiomyopathyLICA2025NCT07766135
Liver and Coagulation Disorders in Cardiac Transthyretin Amyloidosis
An observational study of Transthyretin (TTR) Amyloid Cardiomyopathy and Cardiac Amyloidosis, run by University of Messina at 1 site in Italy.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Transthyretin (TTR) Amyloid Cardiomyopathy, Cardiac Amyloidosis, Cardiomyopathies
- How many people
- 70 participants
- Where
- 1 siteItaly
- Study dates
- 30 Jan 2026to Jan 2028
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: 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.
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
AOU Policlinico G. Martino, UOC Cardiologia con UTIC
Messina, Sicily, 98124
Luigi Colarusso, MD, PhD Candidate, +390902212341, luigi.colarusso@polime.it
Roberto Licordari, MD, PhD
About this study
Official title: 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.
Read more
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.
Read the detailed description
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.
- Conditions
- Transthyretin (TTR) Amyloid Cardiomyopathy, Cardiac Amyloidosis, Cardiomyopathies, Wild-Type Transthyretin Cardiac Amyloidosis, Hereditary Transthyretin Amyloidosis (ATTRv)
- Keywords
- ATTR, ATTR-CA, Cardiac Amyloidosis, Transthyretin Amyloidosis, Tafamidis, Acoramidis, Liver Stiffness, Fibroscan, Liver Dysfunction, Hepatic Congestion, Coagulation Disorder, Hemostasis, Cardiohepatic Syndrome, Biomarkers, Disease Staging, Echocardiography, Heart Failure, Wild-Type ATTR, Hereditary ATTR
- Medical subject headings
- Amyloid Neuropathies, Familial, Cardiomyopathies, Amyloidosis, Hereditary, Transthyretin-Related, Liver Diseases, Hemostatic Disorders, Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Liver Stiffness Measured by Transient Elastography (FibroScan)
Liver stiffness expressed in kilopascals (kPa) measured by transient elastography (FibroScan) in ATTR-CA patients and controls.
Measured: Baseline, 6 Months, 12 Months
Controlled Attenuation Parameter (CAP) Measured by FibroScan
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.
Measured: Baseline, 6 months, 12 months
Serum Aspartate Aminotransferase (AST/GOT)
Serum AST/GOT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
Measured: Baseline, 6 months, 12 months
Serum Alanine Aminotransferase (ALT/GPT)
Serum ALT/GPT concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Serum Gamma-Glutamyl Transferase (GGT)
Serum gamma-glutamyl transferase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Serum Alkaline Phosphatase (ALP)
Serum alkaline phosphatase concentration (U/L) measured by routine laboratory testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Serum Bile Acids
Serum bile acid concentration (mcmol/L) measured by laboratory testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Total Bilirubin (mg/dL)
Serum total bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Direct Bilirubin (mg/dL)
Serum direct bilirubin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Serum Albumin (g/dL)
Serum albumin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Serum Gamma Globulins (g/dL)
Serum gamma-globulin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Serum Immunoglobulin M (IgM) (g/L)
Serum IgM concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Serum Ferritin (ng/mL)
Serum ferritin concentration measured by laboratory testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Anti-Mitochondrial Antibodies
U/ml
Measured: baseline, 6 months, 12 months
Fibrosis-4 (FIB-4) Index
FIB-4 index calculated from age, AST, ALT, and platelet count, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Portal Vein Diameter Assessed by Liver Ultrasound
Portal vein diameter (mm) measured by liver ultrasound, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Portal Vein Flow Velocity Assessed by Doppler Ultrasound (cm/s)
Portal vein blood flow velocity measured by Doppler ultrasound, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Spleen Diameter Assessed by Ultrasound (mm)
Spleen diameter measured by abdominal ultrasound, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Prothrombin Time (PT) (s)
Prothrombin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Activated Partial Thromboplastin Time (aPTT) (s)
Activated partial thromboplastin time measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
International Normalized Ratio (INR)
International normalized ratio (INR) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Plasma Fibrinogen
Plasma fibrinogen concentration (g/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Fibrin/Fibrinogen Degradation Products
Fibrin/fibrinogen degradation products concentration (mcg/Lm) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: Baseline, 6 months, 12 months
D-Dimer
D-dimer concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Alpha-2-Antiplasmin
Alpha-2-antiplasmin concentration (UI/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Antithrombin
Antithrombin concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Plasminogen
Plasminogen concentration (IU/ml) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Thrombin-Antithrombin Complex
Plasma fibrinogen concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Plasmin-Alpha-2-Antiplasmin Complex
Plasmin-Alpha-2-Antiplasmin Complex concentration (ng/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Prothrombin Fragment 1+2
Prothrombin Fragment 1+2 concentration (pmol/L) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Coagulation Factor X
Coagulation Factor X concentration (IU) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
von Willebrand Factor Antigen
von Willebrand Factor Antigen concentration (IU/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Plasminogen Activator Inhibitor-1 (PAI-1)
Plasminogen Activator Inhibitor-1 concentration (U/mL) measured by standard laboratory coagulation testing, compared between patients with ATTR-CA and controls.
Measured: baseline, 6 months, 12 months
Secondary outcomes (6)
Correlation Between Liver Stiffness (kPa) and NT-proBNP (ng/L)
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.
Measured: Baseline
Correlation Between Liver Stiffness and Interventricular Septal Thickness (mm)
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.
Measured: Baseline
Correlation Between Liver Stiffness (kPa) and Left Ventricular Global Longitudinal Strain (GLS %)
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.
Measured: Baseline
Correlation Between Prothrombin Fragment 1+2 (pmol/L) and NT-proBNP (ng/L)
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.
Measured: Baseline
Change in Liver Stiffness During Disease-Modifying Treatment
Change in liver stiffness measured by FibroScan and expressed in kPa from baseline to 6±1 months and 12±1 months after treatment initiation.
Measured: Baseline, 6±1 months, and 12±1 months
Change in Controlled Attenuation Parameter During Disease-Modifying Treatment
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.
Measured: Baseline, 6±1 months, and 12±1 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Aug 2026
- Study start30 Jan 2026
- Primary completionJan 2028 (estimated)
- Study completionJan 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Transthyretin (TTR) Amyloid CardiomyopathyStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 70 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Messina
- Sponsor type
- University, hospital or other
- Collaborators
- Azienda Ospedaliera Universitaria Policlinico "G. Martino"
- Responsible party
- Principal investigator, Gianluca Di Bella, Azienda Ospedaliera Universitaria Policlinico "G. Martino"
- Investigators
- Gianluca Di Bella, MD, PhD, Study chair, University of Messina and AOU Policlinico G. MartinoLuigi Colarusso, MD, PhD Candidate, Principal investigator, AOU Policlinico G. Martino
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07766135
- Sponsor's protocol ID
- CEL Messina Prot. 28-25
- Other IDs
- Delibera n. 63/2026
- Acronym
- LICA2025
- Status last verified
- Jun 2026
- First submitted
- 12 Jun 2026
- Last updated
- 14 Aug 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: 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.