The Differential Effects of 3 Different Immunosuppressive

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00729248
Recruitment Status : Completed
First Posted : August 7, 2008
Results First Posted : August 28, 2013
Last Update Posted : August 28, 2013
Astellas Pharma US, Inc.
Information provided by (Responsible Party):
Lorenzo Gallon, 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.

Condition or disease
Immunosuppression Kidney Transplantation

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 Type : Observational
Actual Enrollment : 12 participants
Time Perspective: Cross-Sectional
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 Start Date : July 2008
Actual Primary Completion Date : July 2009
Actual Study Completion Date : January 2010

Primary Outcome Measures :
  1. CD4+CD25 High FOXP3+ Cell Levels in Mixed Lymphocyte Reactions (MLRs) of Renal Pre-transplant Recipients/Donors [ Time Frame: 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.

Biospecimen Retention:   Samples With DNA
White Cells.

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population
Six to Twelve preoperative renal transplant living donor pairs.

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00729248

United States, Illinois
Northwestern Memorial Hospital
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Astellas Pharma US, Inc.
Principal Investigator: Lorenzo Gallon, MD Northwestern University

Responsible Party: Lorenzo Gallon, Study Principal Investigator, Northwestern University Identifier: NCT00729248     History of Changes
Other Study ID Numbers: KV-08-001
First Posted: August 7, 2008    Key Record Dates
Results First Posted: August 28, 2013
Last Update Posted: August 28, 2013
Last Verified: May 2013

Keywords provided by Lorenzo Gallon, Northwestern University:
Kidney Transplantation
Graft Rejection

Additional relevant MeSH terms:
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs