MedTrace Logo

Procurement of Leukapheresis Products From End Stage Liver Disease (ESLD) Patients for Immunological Studies

NCT02447926 · Status: TERMINATED · Phase: NA · Type: INTERVENTIONAL · Enrollment: 1

Last updated 2019-09-25

Study results available
· View outcomes & findings →

Summary

Regulatory CD4+CD25+ T cells (Treg) derived from the thymus and/or periphery can control immune responsiveness to auto- and allo-antigens. However, there have been few efforts to harness the therapeutic potential of isolated Tregs to control graft rejection and inducing transplantation tolerance in solid organ recipients. In order for Tregs to be used as a clinical treatment, the following properties are necessary: ex vivo generation of sufficient numbers of cells, migration in vivo to sites of antigenic reactivity, ability to suppress rejection in an alloantigen-specific manner, and survival/expansion after infusion. The and others have demonstrated 1) the feasibility of expanding Treg ex vivo, 2) the ability of these cells to down-regulate allogeneic immune responses in vitro, and 3) the efficacy of Treg for prevention of allograft rejection in animal models. In kidney transplant, the investigators have developed strategies for the ex vivo expansion of naturally occurring human Tregs (nTregs) from leukapheresis products that would allow for the clinical employment of this cellular therapy. The investigators are also interested in this approach in patients with end stage liver disease (ESLD) undergoing liver transplantation (LT). Our central hypothesis is that alloreactive human nTreg with suppressive action can be expanded ex vivo from ESLD patients (this proposal) and used to both prevent liver transplant rejection and facilitate the minimization and withdrawal of drug-based immunosuppression (future proposals). This application will further define and validate efficient methods for ex vivo expansion of human CD4+CD25+CD127- FOXP3+nTregs cells in ESLD. The investigators herein propose to use leukapheresis products obtained from patients with ESLD to further refine and optimize protocols for expansion of Tregs. Suppressive function of expanded cells will be assessed using in vitro assays of alloreactivity (mixed lymphocyte culture).

Conditions

  • End Stage Liver Disease

Interventions

PROCEDURE

Leukapheresis

Catheter placement will occur for about 1 hour. The research nurse will schedule leukapheresis on the next day following catheter placement. On the day of leukapheresis, a blood draw will monitor blood counts, kidney function, liver function, and blood clotting ability. Vital signs will be checked three times over the course of intervention. During the procedure, blood is mixed with anticoagulant and separated (i.e. red blood cells, white blood cells, platelets, and plasma). 1-1.5 cups of white blood cells will be collected. Leukapheresis will last 3-6 hours. Remaining components, except for 100-200 ml of plasma, are returned through the catheter. Two teaspoons of blood will be drawn to determine when catheter removal can occur. This part of intervention lasts about 2.5-4 hours.

Sponsors & Collaborators

Principal Investigators

  • Josh Levitsky, MD · Northwestern University

Study Design

Allocation
NA
Purpose
OTHER
Masking
NONE
Model
SINGLE_GROUP

Eligibility

Min Age
18 Years
Max Age
89 Years
Sex
ALL
Healthy Volunteers
No

Timeline & Regulatory

Start
2014-07-31
Primary Completion
2016-07-31
Completion
2016-07-31

Countries

  • United States

Study Locations

More Related Trials

Entities

Companies

Read the full study record

This page highlights key information. For complete eligibility criteria, study locations, investigator contacts, and the full protocol, visit the original record on ClinicalTrials.gov.

View NCT02447926 on ClinicalTrials.gov