Effect of Thymoglobulin Versus Basiliximab on Regulatory T Cell Function in Live Donor Kidney Transplant Recipients (TReg Kidney)

August 26, 2022 updated by: University of Pennsylvania
This study aims to study the effects that two standard of care immunosuppression induction regimens have on regulatory T cells (Treg) in live donor renal transplant recipients. Both regimens are currently used in this hospital for early immunosuppression induction but the effects on Treg numbers and function is not well understood and likely will impact long term immune function.

Study Overview

Status

Terminated

Detailed Description

This study aims to study the effects that two standard-of-care immunosuppression induction regimens have on regulatory T cells (Treg) in live donor renal transplant recipients. These two regimens use anti-T cell antibodies: thymoglobulin is a polyclonal anti-T cell preparation and basiliximab is a monoclonal anti-cluster of differentiation (CD) 25 antibody. Both are currently used in this hospital for early immunosuppression induction but the effects on Treg numbers and function is not well understood and may impact long term immune function. The investigators wish to study the effects that these standard regimens have on Treg numbers, function, and FoxP3 methylation status (an indicator of Treg function). Live donor renal transplant patients with no panel reactive antibodies (PRA) have low risk of early allograft rejection and in various transplant centers are treated with no anti-T cell immunosuppression induction or induction with thymoglobulin or basiliximab as standard of care. Most patients in this hospital receive thymoglobulin but basiliximab is used as well. There are no proven long term benefits to either approach but each seems to lower the risk of short term acute cellular rejection. Both of these agents have been shown to affect numbers of Tregs (as they are T cell subsets) but data does not exist on the duration of these effects or the effects that these agents have on Treg potency or Treg FoxP3 methylation status. Since Tregs are believed to be important in long term control of immune responses, it is possible that the reason these agents do not improve long term results in spite of their short term improvement in rejection rate is due to effects on Treg.

T cell depletion by antibody has become standard of care in the majority of renal transplant programs in the country (including Penn) and this may have reduced short term acute rejection episodes within the first year of transplant. There have unfortunately not been corresponding improvements in long term outcomes and, in fact, the average half life of a renal graft is minimally changed in 2010 compared to 1995. This has been attributed to unresolved issues in diagnosing and treating what is described as "chronic allograft nephropathy" - which in real terms, is probably a longstanding chronic rejection that may be in part due to a mixed T and B cell antigraft response. Despite the fact that these agents are used regularly in clinical transplantation, little is known about their effects on regulatory T cell (Treg) numbers and suppressive activity and nothing is known about effects on the methylation status of Tregs, which seems to correlate with their function. These are novel questions that are a) relevant to clinical practice since these agents are being used in renal transplantation already, b) may yield information that could alter best practices, and c) will yield more basic information about Tregs in human transplantation that will be relevant to future study. There have been few papers that have looked predominantly at a few immunosuppressive agents and numbers of Tregs (this is a low quality statistic since the markers of Tregs are shared by other cell types and thus the "numbers" can be hard to interpret) but little about function or methylation. The investigators propose to randomize 30 live donor kidney recipients to receive either thymoglobulin or basiliximab immunosuppression and thereafter receive standard of care maintenance immunosuppression determined by the clinical team. Both of these regimens are used as standard of care in this hospital. The investigators will enroll only patients with low immunological risk (0-10% PRA) and who are receiving an Blood Type (ABO) compatible transplant. After the initial randomization, all further decisions regarding immunosuppression will be made by the clinical team independent of the study. The investigators will draw blood samples pre-transplant, 3 months after transplant, and 6 months and 12 months after transplant.

Study Type

Observational

Enrollment (Anticipated)

30

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • University of Pennsylvania

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 70 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Live donor renal transplant recipients

Description

Inclusion Criteria:

  • adult patients receiving first live donor kidney transplant. 0-10% panel reactive antibody

Exclusion Criteria:

  • HIV positive, hepatitis C positive, pregnancy, inability to provide informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Thymoglobulin
blood specimen collection
Periodic blood collection to monitor Treg cells
Other Names:
  • Anti-thymocyte globulin
Basiliximab
blood specimen collection
Periodic blood collection to monitor Treg cells
Other Names:
  • Simulect

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Absolute Treg number Cells
Time Frame: 5 years
Each sample will be measured by flow cytometry. Data will be analyzed for each treatment arm using nonparametric statistical tests and expressed as the medium value and inter-quartile range.
5 years
Treg function tested by flow cytometry.
Time Frame: 5 years
T cells and Tregs will be isolated. T cells will be labeled with CFSE and induced to proliferate by addition of CD3 mAb. Data will be evaluated by nonparametric methods.
5 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Treg methylation
Time Frame: 5 years
An indicator of Treg function will be determined by purifying Tregs and monitoring methylation after bisulphate conversion and DNA sequencing. Percentages of methylated CpG sites/samples and will be compared by nonparametric statistics.
5 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Matthew L Levine, MD, University of Pennsylvania

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

November 1, 2010

Primary Completion (ACTUAL)

April 1, 2020

Study Completion (ACTUAL)

April 1, 2020

Study Registration Dates

First Submitted

March 24, 2016

First Submitted That Met QC Criteria

March 31, 2016

First Posted (ESTIMATE)

April 6, 2016

Study Record Updates

Last Update Posted (ACTUAL)

September 1, 2022

Last Update Submitted That Met QC Criteria

August 26, 2022

Last Verified

August 1, 2022

More Information

Terms related to this study

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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