Evaluation of Cirrhotic Cardiomyopathy by Cardiac MRI in Patients Waiting for Liver Transplant.

NCT06327308 | Not Yet Recruiting

• 1 other identifier: 2023/803
• Study Type: observational
• Target: 60
• Locations: 1 country
• Sites: 4

Brief Summary

The aim of this multicenter prospective observational pilot study is to describe the evolution of myocardial fibrosis in cirrhotic patients before and after liver transplantation (LT). Through multimodal analysis of myocardial function and architecture, and analysis of specific markers of inflammation, we aim to explore the following hypotheses: 1) systemic inflammation promotes myocardial fibrosis in cirrhotic patients and could be an early marker of cirrhotic cardiomyopathy; 2) LT allows resolution of myocardial fibrosis by preventing the bacterial translocation that favors the development of deleterious systemic inflammation.

Conditions

Cirrhosis

Keywords

Cirrhosis; cirrhotic cardiomyopathy; Liver Transplantation; MRI

Outcome Measures

Primary Outcomes (1)

• Primary outcome measure

  Difference in myocardial extracellular volume (MECV) on cardiac MRI between the pre-LT visit (visit 2) and 12 months after LT (visit 3). If patients are transplanted less than 6 months after the inclusion visit, visit 2 will not be performed and the reference visit will be visit 1.

  sixth month-21th month after inclusion

Secondary Outcomes (6)

• Prevalence of cirrhotic cardiomyopathy according to 2019 criteria [Izzy M, et al. Hepatology 2020;71:334-45], echocardiographic signs of left ventricular systolic and diastolic dysfunction :

  33 months

• Analysis of the association between myocardial extracellular volume (MECV) (explained variable) and plasma 3-HM concentration (explanatory variable).

  33 months

• Analysis of the association between myocardial extracellular volume (MECV) and the concentration of markers of inflammation (CRP, procalcitonin, copeptin, IL-6) and proteins modulating the degree of inflammation (LBP, PLTP, CETP).

  33 months

• Analysis of the association between the difference in MECV in transplant recipients between visit 2 and visit 3 according to the degree of immunosuppression, measured by mean residual tacrolemia in the 12 months post-LT.

  sixth month-21th month after inclusion

• Number, type and cumulative incidence of cardiovascular events (heart failure, rhythm disorders, etc.) according to cirrhotic cardiomyopathy status occurring between inclusion and LT.

  33 months

Study Arms (1)

Patient with cirrhosis requiring liver transplantation

Diagnostic Test: MRI; Biological: Blood sampling

Interventions

MRI DIAGNOSTIC_TEST

The examination lasts between 45 minutes and one hour. The patient lies down in the MRI tube. He is fitted with headphones that muffle the noise produced by the machine and enable him to receive instructions from the technician. Four electrodes are applied to his chest to continuously record his heartbeat. Finally, his chest is covered with a plastic plate, which receives the MRI signals needed to form the image. Acquiring an MRI image takes between 2 and 20 seconds. To ensure that image quality is not impaired by respiratory movements, images are acquired in apnea. The technician will ask the patient to hold his or her breath repeatedly throughout the examination.

Patient with cirrhosis requiring liver transplantation

Blood sampling BIOLOGICAL

Additional blood will be drawn for dosing acylcarnitines, copeptin, interleukin-6 (IL-6), LPS-Binding Protein (LBP), Phospholipid TransferProtein (PLTP)/Cholesteryl Ester Tranfer Protein (CETP) activity, and for plasma banking. The volume of blood will be 20 ml in total (5 ml for each assay) at each visit. Patients participating in this study will have 3 visits. Total blood volume will therefore be 20 x 3, or 60 ml for the 3 visits.

Patient with cirrhosis requiring liver transplantation

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Any patient with cirrhosis requiring LT and eligible for LT according to a pre-liver transplant assessment that does not contraindicate LT. Patients listed for fulminant hepatitis or early re-transplantation will be excluded.

You may qualify if:

• Women who have been menopausal for at least 24 months, surgically sterilized, or, for women of childbearing age, use an effective method of contraception (oral contraceptives, contraceptive injections, intrauterine devices, double-barrier method, contraceptive patches)
• Signature of an informed consent form indicating that the subject has understood the purpose and procedures required by the study and that he or she agrees to participate in the study and to comply with the requirements and restrictions inherent in the study
• Patient with a social security system or beneficiary of such a system.

You may not qualify if:

• Minor or over 70 years old
• Transplant Patient
• Patient with a TIPS
• Known cardiorespiratory disease including portopulmonary hypertension and coronary artery disease
• Uncontrolled hypertension with interventricular septal thickness ≥ 15 mm
• Hemodynamic instability
• Type 1 diabetes
• Current bacterial infection
• HIV infection (or unknown HIV status)
• Contraindications for MRI including pacemaker, implantable defibrillators, electrosystolic pacing probe, Swan-Ganz probe, postoperative epicardial electrodes, Starr-Ewards metal ball valves, insulin pumps, ferromagnetic vascular clips, ocular and otological implants, ocular ferromagnetic foreign bodies, renal failure with a GFR \< 30 mL/min/1.73 m², contraindication to contrast media, patient unable to maintain apnea for a few seconds, claustrophobia
• Inability to receive informed information in patients with severe encephalopathy who do not have a trusted person
• Refusal to agree to participation by signing the information and consent form as defined
• Patient under guardianship, curatorship, Legal incapacity or limited legal capacity
• Patient deprived of liberty
• Pregnant woman or breastfeeding

Sponsors & Collaborators

• Centre Hospitalier Universitaire de Besancon: lead

Study Sites (4)

CHU Besancon - Hopital Minjoz

Besançon, 25000, France

Location

CHU Dijon - Hopital François Mitterrand

Dijon, 21000, France

Location

CHRU Nancy - Hôpital de Brabois

Nancy, 54000, France

Location

CHU Strasbourg - Hopital de HautePierre

Strasbourg, 67000, France

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

Plasma

MeSH Terms

Conditions

Fibrosis

Interventions

Blood Specimen Collection

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Specimen Handling; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Punctures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Thierry THEVENOT, MD, PHD

  Centre Hospitalier Universitaire de Besancon

  STUDY DIRECTOR

• Delphine WEIL, MD

  Centre Hospitalier Universitaire de Besancon

  PRINCIPAL INVESTIGATOR

• Camille BESCH, MD

  CHU Strasbourg

  PRINCIPAL INVESTIGATOR

• Mouni BENSENANE -OUSSALAH, MD

  CHRU Nancy

  PRINCIPAL INVESTIGATOR

• Marianne LATOURNERIE, MD

  CHU Dijon

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Delphine WEIL, MD, PHD

CONTACT

+33381669457; dweil@chu-besancon.fr

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2024
• First Posted: March 25, 2024
• Study Start: September 1, 2024
• Primary Completion: September 1, 2025
• Study Completion (Estimated): June 1, 2027
• Last Updated: July 10, 2024

Record last verified: 2023-09

Locations

FR (4)