Clinical trial NCT02633826: Pre-formed Alloreactivity in Renal Transplant Recipients
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Kidney Transplantation
Acute Graft Rejection
Keywords: alloreactive T cell
donor-specific antibody
Lead sponsor: Universität des Saarlandes
Sponsor class: OTHER
First posted: 2015-12-17
Enrollment: 190
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Transplant recipients of a kidney from a living donor

Brief 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.

Detailed 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.

Eligibility criteria: 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 (\&amp;lt; 400/µl)

Primary outcomes:
measure: graft function
timeFrame: 1 year
Secondary outcomes:
measure: Creatinine
timeFrame: 1 year
measure: Cystatin C
timeFrame: 1 year
measure: rejection: acute rejection episodes within the first year
timeFrame: 1 year
measure: proteinuria within the first year
timeFrame: 1 year
Other outcomes:
Locations:
city: Homburg
country: Germany
facility: Saarland University
state: Saarland
city: Aachen
country: Germany
facility: Medizinische Klinik II, Aachen University
city: Berlin
country: Germany
facility: Charité Berlin
city: Erlangen
country: Germany
facility: University Erlangen Nürnberg
city: Frankfurt
country: Germany
facility: Medizinische Klinik III, Frankfurt University
city: Gießen
country: Germany
facility: University Clinic of Giessen and Marburg (UKGM)
city: Hamburg
country: Germany
facility: Universitätsklinikum Hamburg Eppendorf
city: Heidelberg
country: Germany
facility: Transplantationszentrum Heidelberg - Nephrologie
city: Köln
country: Germany
facility: Klinikum Köln-Lindenthal
city: Lubeck
country: Germany
facility: University of Lübeck
city: Mainz
country: Germany
facility: University of Mainz
city: Muenster
country: Germany
facility: University of Münster
city: Tübingen
country: Germany
facility: Innere Medizin IV, University of Tübingen
Study officials:
References: