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

NCT02447926 | Terminated Results

• 1 other identifier: STU00097231
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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

Keywords

leukapheresis; regulatory T cells; liver transplantation

Outcome Measures

Primary Outcomes (2)

• Number of Regulatory CD4+CD25+ T Cells Obtained From 150 ml of Peripheral Blood in an ESLD Patient

  Number of regulatory CD4+CD25+ T cells after 21 days in culture from leukapheresis product (150 ml of processed blood) from ESLD patient.

  21 days

• Suppressive Function of Expanded Cells Will be Assessed Using in Vitro Assays of Alloreactivity (Mixed Lymphocyte Culture)

  Assay testing - Suppressive function of expanded cells will be assessed using in vitro assays of alloreactivity (mixed lymphocyte culture). The in vitro assays will test whether the expanded Tregs will retain their suppressive function.

  21 days

Study Arms (1)

Leaukapheresis of End Stage Liver Disease Patients

OTHER

Leukapheresis. All subjects will receive the same treatment arm.

Procedure: Leukapheresis

Interventions

Leukapheresis PROCEDURE

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.

Leaukapheresis of End Stage Liver Disease Patients

Eligibility Criteria

• Age: 18 Years - 89 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \>18 years old,
• ESLD MELD \<25,
• No recent infection,
• no hepatic decompensation,
• no history of HIV,
• weight \> 110 lbs,
• platelets \> 50,000,
• HGB \>10,
• no prior organ transplant

You may not qualify if:

• Patients ineligible for liver transplant,
• patients who do not understand why the study procedures are being conducted,

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University Comprehensive Transplant Center

Chicago, Illinois, 60611, United States

Location

MeSH Terms

Conditions

End Stage Liver Disease

Interventions

Leukapheresis

Condition Hierarchy (Ancestors)

Liver Failure; Hepatic Insufficiency; Liver Diseases; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Cytapheresis; Biological Therapy; Therapeutics; Blood Component Removal; Leukocyte Reduction Procedures; Cell Separation; Cytological Techniques; Clinical Laboratory Techniques; Investigative Techniques

Limitations and Caveats

We stopped the study after one subject was enrolled because this generated enough data to support the ability to expand Tregs in our clinical laboratory to apply for a grant through the Immune Tolerance Network. Additional patients were not needed.

Results Point of Contact

• Title: Dr. Josh Levitsky
• Organization: Northwestern University

j-levitsky@northwestern.edu

312-695-4837

Study Officials

• Josh Levitsky, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Medicine

Study Record Dates

• First Submitted: April 17, 2015
• First Posted: May 19, 2015
• Study Start: July 1, 2014
• Primary Completion: July 1, 2016
• Study Completion: July 1, 2016
• Last Updated: September 25, 2019
• Results First Posted: September 25, 2019

Record last verified: 2019-08

Locations

US (1)