Serum GLYcomics to Predict Graft Loss and Mortality After Liver Transplantation

NCT ID: NCT05866796

Last Updated: 2024-05-16

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 600 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-04-26
• Study Completion Date: 2027-05-01

Brief Summary

The first 12 months after liver transplantation (LT) are decisive in posttransplant outcome, as almost half of deaths and two thirds of graft loss requiring retransplant occur in the first year after LT. Since delaying retransplantation in those patients that experience an unfavorable posttransplant course directly impacts their outcome, timely decision making is of paramount importance in these individuals. However, balancing the need and right timing for retransplantation in individual patients with a complicated posttransplant course is currently a difficult challenge that relies on imperfect clinical variables and biomarkers, as well as the experienced judgment of the transplant team.

Building on the findings of a pilot study in liver transplant recipients (n = 131) led by the Ghent University Hospital, we want to validate the prognostic performance of the GlycoTransplantTest on a multicentric scale. In this pilot study, a single glycomic signature at day 7 after LT allowed accurate prediction of graft loss at 3 months after LT. The serum glycome of those patients experiencing graft loss was characterized by increased undergalactosylation and an increased presence of fucosylated and triantennary glycans. After statistical modeling, use of an optimized cutoff based on the relative abundance of 13 serum glycans showed a strong association with graft loss at 3 months (odds ratio 70.211; P<0.001; 95% CI: 10.876-453.23).

Using sequential measurements of serum glycomics in liver transplant recipients, we want to prospectively study and validate the predictive value of the serum glycomic signature for graft survival and overall survival at 3-months (primary end point) and 12-months after liver transplantation (secondary end point).

Determination of the serum glycomic profile is a high-throughput technique that allows to study and quantify the relative abundance of sugar chains (glycans) anchored at specific sites of serum proteins. This technique has shown a very strong prognostic value for graft loss at 3-months after liver transplantation in a pilot study at the Ghent University Hospital.

In this large-scale multicentric prognostic study, we will collect serum samples of liver transplant recipients at fixed time points.

Apart from the serum glycomic profile, we will collect data from the patients electronic record: demographic data (gender, age), data directly relevant to the indication of transplant (eg. imaging for primary liver cancer, lab values for diagnosis of end-stage liver disease), and outcome data (graft survival, overall survival, follow-up time). This list is non-exhaustive.

Using this approach, we will demonstrate the predictive validity of serum glycomics in liver transplant recipients for graft survival and overall survival at 3- and 12-months post-LT. Building on these data, the use of a simple blood test could differentiate patients at risk of graft loss and thus represent a paradigm shift directing these patients to timely treatment adaptations.

Conditions

Liver Transplant Failure; Prognostic Biomarkers

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

No graft loss

Patients receiving liver transplantation that do NOT experience graft loss within 3-months or 12-months after liver transplantation.

GlycoTransplantTest

Intervention Type: DIAGNOSTIC_TEST

Determination of serum glycomics in the early posttransplant stage, using an optimal cutoff based on statistic modeling.

Graft loss

Patients receiving liver transplantation that experience graft loss within 3-months or 12-months after liver transplantation.

Graft loss is defined as either death of the liver transplant recipient (all-cause), or need for retransplantation of the liver.

GlycoTransplantTest

Intervention Type: DIAGNOSTIC_TEST

Determination of serum glycomics in the early posttransplant stage, using an optimal cutoff based on statistic modeling.

Interventions

GlycoTransplantTest

Determination of serum glycomics in the early posttransplant stage, using an optimal cutoff based on statistic modeling.

Intervention Type: DIAGNOSTIC_TEST

Eligibility Criteria

Inclusion Criteria

• Signed and dated patient informed consent document
• Age ≥ 18 years
• Ability to comply with protocol-specified evaluations and scheduled visits
• Diagnosis of end-stage liver disease, primary hepatic malignancy meeting the Milan criteria for liver transplantation, or acute hepatic failure
• Eligible for liver transplantation and/or active on the waiting list for liver transplantation. Individuals eligible and/or active on the waiting list for multiple organ transplantation including the liver (eg. Combined liver and kidney transplantation, or intestinal transplantation) are also eligible for inclusion.
• Consulted the department of Gastroenterology and Hepatology at Ghent University Hospital

Exclusion Criteria

• Transplantation of one or more organs not including the liver

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fund for Scientific Research, Flanders, Belgium

OTHER

Sponsor Role: collaborator

University Hospital, Antwerp

OTHER

Sponsor Role: collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: collaborator

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

OTHER

Sponsor Role: collaborator

University Hospital, Ghent

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Xavier Verhelst

Ghent, Flanders, Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Xavier Verhelst, MD, PhD

Role: CONTACT

xavier.verhelst@uzgent.be

0032 9 332 23 71

Lorenz Grossar, MD

Role: CONTACT

lorenz.grossar@uzgent.be

0032 494 088 789

Facility Contacts

Xavier Verhelst, MD, PhD

Role: primary

xavier.verhelst@uzgent.be

+3293322371

Lorenz Grossar, MD

Role: backup

lorenz.grossar@uzgent.be

+32494088789

Other Identifiers

ONZ-2023-0061

Identifier Type: -

Identifier Source: org_study_id