Pre-formed Alloreactivity in Renal Transplant Recipients

Kidney Transplantation Clinical Trial

Official title:

The Role of Pre-formed Alloreactive T Cells on Acute Rejection Episodes and Long-term Graft Outcome in Patients After Living Donor Renal Transplantation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02633826
• Other study ID #: Pre-formed alloreactivity
• Status: Completed
• Start date: November 2015
• Est. completion date: March 2023

Study information

• Verified date: April 2024
• Source: Universität des Saarlandes
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This investigator-initiated study will analyse the role of pre-formed alloreactive T cells on acute rejection episodes and graft outcome in kidney transplant recipients after living donation.

Description:

In recipients of solid organ transplants, preformed alloreactive T cells may mediate acute rejections and compromise long-term graft survival. Previous studies on the role of alloreactive T cells in transplantation were hampered by the fact that experimental assays to quantify alloreactivity were technically demanding and not suitable for use in a clinical setting. Based on a recent development of a whole-blood assay, alloreactive T cells may be quantified and characterised within one day. This assay therefore provides the experimental basis to study the development and the role of alloreactive T cells in a clinical setting in patients after renal transplantation. This will be performed in a multicenter study in living donor renal transplant recipients where preformed alloreactivity of the recipient towards the living donor will be determined and associated with standard clinical parameters of graft function and long-term graft outcome on follow-up. In addition, the development of donor-specific antibodies will be analysed after transplantation. If this project was able to provide evidence for a role of alloreactive T cells in acute rejection episodes or long-term graft function, this assay may in future be used to guide individualized immunosuppressive drug treatment early after transplantation. It will thereby aid in distinguishing patients where standard immunosuppressive drug regimens are sufficient from the minor population of patients at high risk for rejection who will benefit from intensified drug regimens.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 190
• Est. completion date: March 2023
• Est. primary completion date: March 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• Written informed consent

• First or second renal transplantation

• Living donor renal transplantation

• Recipient older than 18 years

• Negative cross match

• Planed quadruple, Tacrolimus-based (low-dose) immunosuppressive drug regimen (Tacrolimus, 2g MMF starting dose, (methyl)prednisolone according to center practice, basiliximab at day 0 and day 4)

• Planned start of Tacrolimus (Advagraf®) 3 to 10 days prior to transplantation (trough levels 5-10 ng/ml during the first 3 months, 5-7 ng/ml thereafter)

Exclusion Criteria:

• Planed T-cell depleting induction therapy

• Pregnancy

• Pre-existing, moderate to high dose immunosuppressive medication

• Pre-existing, severe lymphopenia (< 400/µl)

Related Conditions & MeSH terms

• Acute Graft Rejection
• Kidney Transplantation

Locations

Country	Name	City	State
Germany	Medizinische Klinik II, Aachen University	Aachen
Germany	Charité Berlin	Berlin
Germany	University Erlangen Nürnberg	Erlangen
Germany	Medizinische Klinik III, Frankfurt University	Frankfurt
Germany	University Clinic of Giessen and Marburg (UKGM)	Gießen
Germany	Universitätsklinikum Hamburg Eppendorf	Hamburg
Germany	Transplantationszentrum Heidelberg - Nephrologie	Heidelberg
Germany	Saarland University	Homburg	Saarland
Germany	Klinikum Köln-Lindenthal	Köln
Germany	University of Lübeck	Lubeck
Germany	University of Mainz	Mainz
Germany	University of Münster	Muenster
Germany	Innere Medizin IV, University of Tübingen	Tübingen

Sponsors (1)

Lead Sponsor	Collaborator
Martina Sester

Country where clinical trial is conducted

Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	graft function	1-year graft function (estimated glomerular filtration rate)	1 year
Secondary	Creatinine	1-year creatinine	1 year
Secondary	Cystatin C	1-year cystatin C	1 year
Secondary	rejection: acute rejection episodes within the first year		1 year
Secondary	proteinuria within the first year		1 year