The Differential Effects of 3 Different Immunosuppressive

Completed

• Conditions: Kidney Transplantation; Immunosuppression

• Registration Number: NCT00729248
• Lead Sponsor: Northwestern University

Brief Summary

The study is a laboratory investigation comparing the regulatory effects of different immunosuppressive therapies in an in vitro human MLR assay of selecting specific immunosuppressive therapy to promote a regulatory profile and determining possibly newer accepted dosing and drug concentrations for agents most associated with this regulatory profile.

Detailed Description

Life-long immunosuppressive (IS) therapy is typically required in the great majority of organ transplants. Immunobiologically correct IS dosing, tapering to low levels and/or monotherapy could lower the incidence of complications related to IS and improve long term graft and patient survival. The current standard of IS care for liver transplant recipients are the calcineurin-inhibitors (CNIs) tacrolimus (TAC) and cyclosporine (CSA), although alternative IS drugs such as mycophenolate mofetil (MMF) and sirolimus (SRL) are available for use in select patients. This is also true for kidney, pancreas and heart transplant recipients, with TAC being favored in each case. The ideal IS agent is one that can be given at low levels such that both rejection and long term toxicity are minimized. Directly related to IS minimization might be the development of a regulatory, "tolerance profile", as assessed by ex vivo immunophenotyping and functional assays that might test these specific IS agents singly, in combination or even in sequence.

Human Tregs and DCregs can be more predominantly generated in the presence of one of three IS agents with different modes of action, i.e., TAC, MMF or SRL, and in different conditions of antigen presentation and alloimmune incompatibility.

This is a bench protocol studying the effects of TAC, MMF and SRL on pre operative living renal recipient donor pair.

Study Timeline

• Study Start: 2008-07
• Study First Submitted: 2008-08-04
• Study First Submitted QC: 2008-08-06
• Study First Posted: 2008-08-07
• Primary Completion: 2009-07
• Study Completion: 2010-01
• Results First Submitted: 2010-08-25
• Status Verified: 2013-05
• Results First Submitted QC: 2013-05-23
• Last Update Submitted: 2013-05-23
• Results First Posted: 2013-08-28
• Last Update Posted: 2013-08-28

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 12

Inclusion Criteria

• Adults 18 years of Age or Older
• Undergoing living donor renal transplant

Exclusion Criteria

• No active infection or history of malignancy
• No HIV infection
• No Hepatitis C (HCV) infection
• No prior transplant (kidney or other organ)
• No chromic use of immunosuppressive therapy or history of autoimmune disease

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
CD4+CD25 High FOXP3+ Cell Levels in Mixed Lymphocyte Reactions (MLRs) of Renal Pre-transplant Recipients/Donors	3 months	CD4+CD25 high FOXP3+ cell levels in mixed lymphocyte reactions (MLRs) of Renal Pre-transplant Recipients/Donors were measured in the presence of 1) No Drug/Control; 2) 0.05-0.2, 0.3-3 and \> 5 ng/ml Tacrolimus (TAC); OR 3) 0.05-0.2, 0.3-3 and \> 5 ng/ml Sirolimus (SRL). CD4+CD25 high FOXP3+ cell levels in the MLRs with TAC or SRL are expressed as the percentage of CD4+CD25 high FOXP3+ cell levels in the MLRs with no drug.

Trial Locations

Locations (1)

Northwestern Memorial Hospital; 🇺🇸 Chicago, Illinois, United States