Clinical trial NCT06734013: Transcriptomics as an Aid in the Histological Diagnosis of Acute Rejection After Liver Transplantation
Official title: Transcriptomics as an Aid in the Histological Diagnosis of Acute Rejection After Liver Transplantation
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Rejection; Transplant, Liver
Keywords: Liver transplant
Lead sponsor: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Sponsor class: OTHER
First posted: 2024-12-16
Enrollment: 40
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: DIAGNOSTIC

Brief summary: The primary objective of this exploratory study is to identify genes associated with acute rejection in liver transplant patients. To this end, a panel of acute rejection indicator genes (both humoral and cell-mediated) will be selected from results published in the literature and applied to biological material derived from biopsies. The secodnary objective is to identify genes associated with the diagnosis of humoral acute rejection and those associated with the diagnosis of cell-mediated acute rejection.

Detailed description: The possibility of introducing molecular diagnostics in support of histological and clinical diagnostics (still not routinely applied today but recommended by the most recent guidelines) will result in faster and more precise diagnostics, capable of highlighting early activation of cellular signals related to rejection in the absence yet of a frank clinical and histological picture. This will lead to a better diagnostic stratification of these patients, with the possibility of rationalising the choice of therapy.

AIMS: The primary objective of this exploratory study is to identify genes associated with acute rejection in liver transplant patients. To this end, a panel of acute rejection indicator genes (both humoral and cell-mediated) will be selected from published results in the literature and applied to biological material derived from biopsies. The secodnary objective is to identify genes associated with the diagnosis of humoral acute rejection and those associated with the diagnosis of cell-mediated acute rejection.

ENDPOINT/S: diagnostic (No of cases) of acute rejection; possible specific diagnosis of acute cell-mediated and humoral rejection.

STUDY DESIGN: The study is single-centre, observational, tissue-based, cross-sectional, exploratory, retrospective and prospective. Approximately 40 patients are expected to be enrolled, 20 retrospective and 20 prospective. All patients will be treated according to clinical practice: clinical and histological data will be collected in pseudonymous form. Routine histological and immunohistochemical investigations as well as RT-PCR analysis will be performed on the biopsy tissue (FFPE material). To assess the diagnostic sensitivity with regard to rejection status, and for panel development, a retrospective cohort of consecutive cases with acute rejection will be enrolled; for the prospective cohort, consecutive patients requiring liver biopsy for diagnostic indications will be enrolled.

STUDY POPULATION: The study will enrol patients undergoing OLT who require a liver biopsy for diagnostic indications. There is no restriction of sex or underlying pathology. Retrospective case enrolment is planned within the first 6 months of 2024. Prospective case enrolment will take place during 2024. Patients will be enrolled at the U.O. of Internal Medicine for the Treatment of Severe Organ Failures, IRCCS - Azienda Ospedaliero-Universitaria di Bologna Policlinico di S. Orsola, where the biopsy will be performed as standard of care.

Eligibility criteria: Inclusion Criteria:

* Patients with a diagnosis of post-OLT rejection prior to the visit at which they will be enrolled, with tissue available for RT-PCR investigations
* Age ≥ 18 years
* Informed consent

Exclusion Criteria:

* Age \<18 years

Primary outcomes:
measure: Identification of genes associated with acute rejection liver transplant.
timeFrame: At the time of biopsy, up to 6 months
Secondary outcomes:
measure: Identification of genes associated with the diagnosis of acute humoral rejection
timeFrame: At the time of biopsy, up to 6 months
measure: Identification of genes associated with the diagnosis of acute cell-mediated rejection
timeFrame: At the time of biopsy, up to 6 months
Other outcomes:
Locations:
city: Bologna
country: Italy
facility: IRCCS Azienda Ospedaliero-Universitaria di Bologna
Study officials:
affiliation: IRCCS Azienda Ospedaliero-Universitaria di Bologna
name: Deborah Malvi, MD
role: PRINCIPAL_INVESTIGATOR
References: