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

NCT ID: NCT02730715

Last Updated: 2022-09-01

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

TERMINATED

Total Enrollment

30 participants

Study Classification

OBSERVATIONAL

Study Start Date

2010-11-30

Study Completion Date

2020-04-30

Brief Summary

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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.

Detailed Description

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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.

Conditions

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KIDNEY TRANSPLANTATION

Study Design

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Observational Model Type

COHORT

Study Time Perspective

PROSPECTIVE

Study Groups

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Thymoglobulin

blood specimen collection

Thymoglobulin

Intervention Type DRUG

Periodic blood collection to monitor Treg cells

Basiliximab

blood specimen collection

Basiliximab

Intervention Type DRUG

Periodic blood collection to monitor Treg cells

Interventions

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Basiliximab

Periodic blood collection to monitor Treg cells

Intervention Type DRUG

Thymoglobulin

Periodic blood collection to monitor Treg cells

Intervention Type DRUG

Other Intervention Names

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Simulect Anti-thymocyte globulin

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Pennsylvania

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Matthew L Levine, MD

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

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University of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Countries

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United States

Other Identifiers

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811893

Identifier Type: -

Identifier Source: org_study_id

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