TruGraf Liver Gene Expression Serial Test

Primary Sclerosing Cholangitis Clinical Trial

Official title:

Usage of TruGraf Liver Gene Expression to Identify Subclinical Rejection as Well as Adjust Immunosuppression Medications in Liver Transplant Recipients Due to Autoimmune Disease

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06061341
• Other study ID #: 202307175
• Status: Not yet recruiting
• Start date: April 2024
• Est. completion date: December 2026

Study information

• Verified date: March 2024
• Source: Washington University School of Medicine
• Contact: Allison Egan, RN, BSN
• Phone: (314) 362-8721
• Email: a.egan[@]wustl.edu
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is an Investigator Initiated, single center, non-randomized, single arm study utilizing TruGraf liver gene expression serial testing in patients with autoimmune liver diseases (AIH, PSC, PBC) monthly for the first 6 months after transplant to help inform immunosuppression (IS) optimization. Approximately 20 patients will be enrolled in the study. Study outcomes will include 1-year graft survival, 1 year BPAR and clinically treated rejection rates, number of changes to IS based on the results of Trugraf, eGFR and immune mediated issues.

TruGraf®, (Transplant Genomics, Inc., a member of Eurofins Transplant Diagnostics) is a non-invasive blood-based test to assist the clinician in lowering immunosuppression in liver transplant patients. It is the first and only blood-based test that offers biomarker guidance to aid physicians in minimizing immunosuppression in transplant recipients. Unfortunately, achieving the tight control of therapeutic levels of immunosuppression that is required to maintain the balance between "too much" and "too little" can be difficult. TruGraf liver can help clinicians confirm immune "quiescence" prior to, as well as following, immunosuppression reduction in patients with stable graft function, minimizing the risk of overt graft injury due to rejection.

The clinical context of use for TruGraf is to provide reassurance to the clinician who is contemplating a preemptive reduction in IS therapy that a patient's immune status is "quiescent" thus reducing the risk of triggering acute rejection with that IS reduction. Having the ability to assess whether the patient's immune status is "quiescent" or activated when considering an increase or decrease in IS therapy allows the clinician greater confidence in decision making.

Description:

Study Abstract Following liver transplantation, organ recipients require long-term immunosuppression therapy along with frequent surveillance of the transplanted graft for indications of rejection, injury or failure. Long-term death rates in liver transplantation are more often attributable to long-term intake of immunosuppression medications than to liver graft dysfunction. Excessive immunosuppression can lead to declining kidney function, recurrent infections and other issues especially in the aging recipient population while suboptimal immunosuppression can lead to allograft injury, rejection or failure.

Monitoring for graft health post-transplant typically relies upon measurements of immunosuppression drug levels, serum liver enzyme testing, clinical symptoms of graft rejection and invasive liver biopsies. The measurement of serum liver enzymes may not reflect the full story as these enzymes are insensitive for predicting immune response and are considered to be late indicators of organ injury and/or damage given that by the time the enzymes are elevated the liver damage may have already occurred.

Currently, the gold standard for the detection of subclinical (before definitive, observable symptoms) graft injury is an invasive liver biopsy. Many times liver grafts will have abnormal histological findings late after transplantation despite having normal liver enzymes. Also, interpretation may be difficult in the presence of infection or recurrence of primary disease. As discussed, standard liver enzyme blood tests are non-specific and have an insensitivity for detecting subclinical graft injury. There is a need for non-invasive biomarkers to predict the onset and severity of rejection and improvement in histological markers to make an accurate diagnosis.

The identification of non-invasive biomarkers for subclinical graft injury to help individualize immunosuppression therapy especially in patients with autoimmune liver diseases will allow for better management of allograft protection along with improved management of adverse side effects. In this study, non-invasive biomarker assessment will be performed, utilizing TruGraf liver gene expression testing, to serially monitor for early immune activation prior to acute rejection with the aim to inform immunosuppression therapy management in liver transplant recipients with autoimmune diseases of the liver.

Primary Hypothesis Can utilization of Trugraf Liver gene expression testing to alter immunosuppression (IS) protocols in liver transplant recipients with autoimmune disease reduce the need for post-transplant liver biopsy as well as 1-year graft rejection rates as compared to a matched historical control group?

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 20
• Est. completion date: December 2026
• Est. primary completion date: November 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Recipients =18 years of age

• Currently waitlisted for liver transplant or recipient of liver transplant within the last 30 days

• Primary indication for transplant due to autoimmune hepatitis (AIH) - Primary Biliary Cirrhosis (PBC) or Primary Sclerosing Cholangitis (PSC) etiologies

• First time, single-organ liver transplant recipient

• Willing and able to undergo protocol required TruGraf serial blood draws

Exclusion Criteria:

• Recipient <18 years of age

• Recipients of multi-organ or repeat transplantation

• Grafts from donors with HIV

• Grafts from donors with viremic Hepatitis A, B, C

• Inability to meet study requirements

Related Conditions & MeSH terms

• Autoimmune Hepatitis
• Autoimmune Liver Disease
• Cholangitis
• Cholangitis, Sclerosing
• Hepatitis, Autoimmune
• Liver Cirrhosis, Biliary
• Liver Diseases
• Primary Biliary Cirrhosis
• Primary Sclerosing Cholangitis

Intervention

Diagnostic Test:
• TruGraf®
TruGraf® is a non-invasive blood-based test to assist the clinician in lowering immunosuppression in liver transplant patients. It is the first and only blood-based test that offers biomarker guidance to aid physicians in minimizing immunosuppression in transplant recipients.

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
Washington University School of Medicine	Transplant Genomics, Inc.

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Graft survival	Organ recipients require long-term immunosuppression therapy along with frequent surveillance of the transplanted graft for indications of rejection, injury or failure.	12 months
Primary	Biopsy-Proven Acute Rejection (BPAR) results	Will be assessed via biopsy	12 months
Primary	Confirmed rejection diagnosis	Based on clinical data including the patient's symptoms and signs and confirmed by laboratory studies of blood and a tissue biopsy.	12 months
Primary	Clinical treatment of rejection	Possible revision to immunosuppressive (IS) medications	12 months
Secondary	Number of changes to immunosuppressive (IS) agents	Based on results of TruGraf liver gene expression test	12 months
Secondary	Number of IS medications	% of patients achieving monotherapy immunosuppression	12 months
Secondary	Immunosuppression reduction	% reduction from baseline	12 months
Secondary	Estimated Glomerular filtration rate (eGFR)	eGFR change from baseline to month 12	12 months
Secondary	Immune mediated issues	Infection incidence	12 months