The Differential Effects of 3 Different Immunosuppressive

Kidney Transplantation Clinical Trial

Official title:

The Differential Effects of 3 Different Immunosuppressive Agents, Tacrolimus Mycophenolate Mofetil and Sirolimus on the Generation of Tregs and DCregs in in Vitro MLR and T Cell Activation Assays

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00729248
• Other study ID #: KV-08-001
• Status: Completed
• Phase: N/A
• First received: August 4, 2008
• Last updated: May 23, 2013
• Start date: July 2008
• Est. completion date: January 2010

Study information

• Verified date: May 2013
• Source: Northwestern University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: January 2010
• Est. primary completion date: July 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Time Perspective: Cross-Sectional

Related Conditions & MeSH terms

• Immunosuppression
• Kidney Transplantation

Locations

Country	Name	City	State
United States	Northwestern Memorial Hospital	Chicago	Illinois

Sponsors (2)

Lead Sponsor	Collaborator
Northwestern University	Astellas Pharma US, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	CD4+CD25 High FOXP3+ Cell Levels in Mixed Lymphocyte Reactions (MLRs) of Renal Pre-transplant Recipients/Donors	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.	3 months	No