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

KIDNEY TRANSPLANTATION Clinical Trial

— TReg Kidney  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT02730715
• Other study ID #: 811893
• Status: Terminated
• Start date: November 2010
• Est. completion date: April 2020

Study information

• Verified date: August 2022
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 30
• Est. completion date: April 2020
• Est. primary completion date: April 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

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

Related Conditions & MeSH terms

• KIDNEY TRANSPLANTATION

Intervention

Drug:
• Basiliximab
Periodic blood collection to monitor Treg cells
• Thymoglobulin
Periodic blood collection to monitor Treg cells

Locations

Country	Name	City	State
United States	University of Pennsylvania	Philadelphia	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absolute Treg number Cells	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
Primary	Treg function tested by flow cytometry.	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	Treg methylation	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