Discovery and Validation of Proteogenomic Biomarker Panels in Liver Transplant Recipients (PROGENI-LI)

Discovery and Validation of Proteogenomic Biomarker Panels in a Prospective Serial Blood and Urine Monitoring Study of Liver Transplant Recipients - Transplant Proteogenomics

The main focus of this study is to develop blood and/or urine tests that will help to detect early signs of rejection in people who have had a liver transplant. Researchers will examine blood, urine, and tissue samples and try to identify markers for certain conditions such as rejection, response to therapy, and scarring of the liver. Additionally, researchers would like to identify biomarkers that can detect damage to the native kidneys before blood levels of creatinine rises. By studying gene expression, researchers hope to be able to diagnose these conditions earlier and improve liver survival.

Study Overview

• Status: Completed
• Conditions: Liver Transplantation; Liver Transplant Recipients

• Study Type: Observational
• Enrollment (Actual): 202

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Northwestern University, Feinberg School of Medicine
  • New York
    • New York, New York, United States, 10029
      • Mount Sinai School of Medicine
  • Ohio
    • Cleveland, Ohio, United States, 44295
      • Cleveland Clinic Foundation
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Medical University of South Carolina
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Liver Transplant Recipients

Description

Inclusion Criteria:

• Subjects undergoing primary deceased-donor or living donor liver transplantation;
• Subject must be able to understand and provide informed consent.

Exclusion Criteria:

• Need for combined organ transplantation;
• Previous solid organ and/or islet cell transplantation;
• Infection with HIV;
• Allergy to iodine;
• Inability or unwillingness of a participant to comply with study protocol;
• Any condition that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Liver Transplant Recipients

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute Rejection	The primary endpoint is the incidence of biopsy proven AR at 3, 12 and 24 months after LT.	3 months after liver transplant
Acute Rejection		12 months after liver transplant
Acute Rejection		24 months after liver transplant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Severity of acute rejection	Severity (initial grade, steroid-responsive vs. refractory by biopsy) and clinical/biochemical resolution following treatment of AR	Baseline (Visit 1) to Month 24 (Visit 12):
Recurrent Hepatitis-C Virus (HCV-R)	Incidence, severity (grade, stage), and treatment (requirement for, response rates) of HCV-R	Baseline (Visit 1) to Month 24 (Visit 12)
Chronic Kidney Disease(CKD)	Incidence, severity (stage, need for renal replacement therapy or kidney transplantation), and response to treatment (CNI reduction/withdrawal ± MPA or mTOR) of CKD	Baseline (Visit 1) to Month 24 (Visit 12)
Incidence of death, graft loss, and need for liver retransplantation		Baseline (Visit 1) to Month 24 (Visit 12)
Incidence of opportunistic infections, malignancy, and cardiovascular complications		Baseline (Visit 1) to Month 24 (Visit 12)
mRNA expression profiles of peripheral blood (AR, HCV-R, CKD)		Baseline (Visit 1) to Month 24 (Visit 12)
mRNA expression profiles of liver biopsies (AR, HCV-R)		Baseline (Visit 1) to Month 24 (Visit 12)
Protein expression profiles of plasma ( AR, HCV-R, CKD)		Baseline (Visit 1) to Month 24 (Visit 12)
Protein expression profiles of urine (CKD)		Baseline (Visit 1) to Month 24 (visit 12)
microRNA Profiling Plasma & Cells		Baseline (Visit 1) to Month 24 (Visit 12)
Multiparameter Flow Cytometry - Viral Pathogens		Baseline (Visit 1) to Month 24 (Visit 12)
Viral Monitoring - EBV & CMV		Baseline (Visit 1) to Month 24 (Visit 12)

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Collaborators: Clinical Trials in Organ Transplantation
• Investigators: Study Chair: Josh Levitsky, MD, MS, Northwestern University Feinberg School of Medicine; Principal Investigator: Michael Abecassis, MD, MBA, Northwestern University Feinberg School of Medicine

Publications and helpful links

Helpful Links

• National Institute of Allergy and Infectious Diseases (NIAID)
• Clinical Trials in Organ Transplantation (CTOT)

Study record dates

Study Major Dates

• Study Start: August 1, 2012
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): December 1, 2015

Study Registration Dates

• First Submitted: August 16, 2012
• First Submitted That Met QC Criteria: August 21, 2012
• First Posted (Estimate): August 24, 2012

Study Record Updates

• Last Update Posted (Estimate): September 2, 2016
• Last Update Submitted That Met QC Criteria: September 1, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: proteogenomic biomarker panels
• Other Study ID Numbers: DAIT CTOT-14

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The plan is to share data in ImmPort, a long-term archive of clinical and mechanistic data from DAIT-funded grants and contracts that also provides data analysis tools that are available to researchers who register online and subsequently receive DAIT approval.