Clinical trial NCT00729248: The Differential Effects of 3 Different Immunosuppressive
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Immunosuppression
Kidney Transplantation
Keywords: Transplants
Kidney Transplantation
Immunosuppression
Assay
Graft Rejection
Lead sponsor: Northwestern University
Sponsor class: OTHER
Collaborators: name: Astellas Pharma US, Inc.
First posted: 2008-08-07
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Time perspective: CROSS_SECTIONAL
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Six to Twelve preoperative renal transplant living donor pairs.

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.

Eligibility criteria: 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

Primary outcomes:
measure: CD4+CD25 High FOXP3+ Cell Levels in Mixed Lymphocyte Reactions (MLRs) of Renal Pre-transplant Recipients/Donors
timeFrame: 3 months
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Northwestern Memorial Hospital
state: Illinois
Study officials:
affiliation: Northwestern University
name: Lorenzo Gallon, MD
role: PRINCIPAL_INVESTIGATOR
References: