ALLoreactive T-Cell receptOr RePertoire in kidnEy tranSpl... | NCT03422224

Studies
ALLoreactive T-Cell receptOr RePertoire in kidnEy tranSplantation

NCT03422224

Sponsor

Medical University of Vienna

Status

Unknown status

Last Update Posted

Oct 23, 2023Actual

Enrollment

50Estimated

Phase

Not provided

Conditions

Renal Transplant Rejection
Immune Repertoire
Transplant; Complication, Rejection
Alloreactivity

Interventions

Mixed lymphocyte reaction

Countries

Austria

Protocol Section

Identification Module Status Module Sponsor/Collaborators Module Oversight Module Description Module Conditions Module Design Module Arms/Interventions Module Outcomes Module Eligibility Module Contacts/Locations Module References Module IPD Sharing Statement Module

Results Section

Participant Flow Module Baseline Characteristics Module Outcome Measures Module Adverse Events Module More Info Module

Annotation Section

Annotation Module

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module Condition Browse Module Intervention Browse Module

Protocol Section

Identification Module

NCT ID

Results Section

No data available

No data is available for this block.

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Version Holder

Status Module

Record Verification Date

Oct 2023

Overall Recruitment Status or Expanded Access Status

Unknown status

Last Known Status

Recruiting

Delayed Posting

Not provided

Why Stopped

Not provided

Expanded Access Info

Start Date

Jul 1, 2017Actual

Primary Completion Date

Jul 2024Estimated

Completion Date

Jul 2024Estimated

First Submitted Date

Jan 30, 2018

First Submission Date that Met QC Criteria

Feb 2, 2018

First Posted Date

Feb 5, 2018Actual

Results Waived

Not provided

Results First Submitted Date

Not provided

Results First Submitted that Met QC Criteria

Not provided

Results First Posted Date

Not provided

Certification/Extension (aka Delayed Results) First Submitted Date

Not provided

Certification/Extension First Submitted that Passed QC Review

Not provided

Certification/Extension First Posted Date

Not provided

Last Update Submitted Date

Oct 20, 2023

Last Update Posted Date

Oct 23, 2023Actual

Oversight Module

Has Data Monitoring Committee (DMC)

Is FDA Regulated Drug

Is FDA Regulated Device

Is Unapproved Device

Not provided

Pediatric Postmarket Surveillance of a Device Product

Not provided

Product Exported from US

Not provided

FDAAA801 Violation

Not provided

Description Module

Brief Summary

In this study, the investigators will establish a workflow to generate unique patterns of the donor-reactive T cell repertoire using mixed lymphocyte reactions to select alloreactive T cell clones prior to transplantation Tissue infiltrating as well as blood bound T cells will be characterized based on:

Identification of donor-specific T cell receptor sequences pre- and post-transplant by in vitro expansion to determine unique patterns
Quantification and comparison of donor-specific T cell clones in kidney biopsy and blood samples.
Analysis of the TCR repertoire diversities derived from kidney biopsy and blood samples and association of repertoire diversities with the histomorphological phenotype of T cell mediated rejection.
Identification of T cell subtypes within the donor-reactive population. The investigators specifically hypothesize that highly expanded donor-reactive T cell clones in both kidney tissue and blood samples at time of indication biopsy are associated with the histological phenotype of acute T cell mediated rejection. The investigators have previously shown that there is a strong correlation between highly expanded tissue-resident T cell clones and the repertoire found in periphery blood samples. To trace and quantify donor reactive T cells the investigators will apply a truly quantitative approach for immune repertoire profiling based on high- throughput sequencing. The investigators ultimate goal is to develop a diagnostic tool to assess alloreactive cellular immunoresponses based on peripheral blood samples.

Detailed Description

Kidney transplant recipients receiving a non lymphodepletional induction therapy at the investigators center will be included in this study.

Alloreactive T cells are defined prior to transplantation via a mixed lymphocyte reaction of donor and recipient PBMC's.

Following transplantation PBMC's will be sampled at management (3 and 12 months) and for-cause biopsies and fifteen patients with histological proven acute T cell mediated rejection will be compared to 15 patients without histopathological signs of alloimmune response in time matched for-cause biopsies.

T cell receptor beta chains of T cells found in the circulation and the allograft biopsy will be sequenced via Next generation sequencing.

Abundance of alloreactive T cells of the overall repertoire pre-and post-transplant and their presence in the allograft will be assessed.

The diversity of the overall repertoire and alloreactive repertoire will be compared between these two groups.

Design Module

Study Type

Observational

Number of References to an Expanded Access Study

Not provided

Expanded Access Types

Not provided

Patient Registry

Target Follow-Up Duration

Not provided

Phases

Not provided

Interventional Study Design

Allocation

Not provided

Intervention Model

Biospecimen

Retention

Enrollment

50Estimated

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Good transplant function		Kidney transplant recipients without histological signs of rejection.	Diagnostic Test: Mixed lymphocyte reaction
Transplant Rejection		Kidney transplant recipinets experiencing a T cell mediated rejection episode.	Diagnostic Test: Mixed lymphocyte reaction

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Mixed lymphocyte reaction	Diagnostic Test	Assessment of alloreactive T cell repertoire	Good transplant function Transplant Rejection

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Rejection	biopsy proven rejection	12 months

Secondary Outcomes

Not provided

Other Outcomes

Not provided

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Kidney transplantation in our center

Exclusion Criteria:

Donor not evaluated by our center

Accepts Healthy Volunteers

Sex

All

Sex/Gender Based

Not provided

Sex/Gender Description

Not provided

Minimum Age

Not provided

Maximum Age

Not provided

Standard Ages

ChildAdultOlder Adult

Study Population

Chronic kidney disease

Sampling Method

Non-Probability Sample

Contacts/Locations Module

Central Contacts

Name	Role	Phone	Extension	Email
Constantin N Aschauer, MD	Contact	00434040043890		constantin.aschauer@meduniwien.ac.at

Overall Officials

Name	Affiliation	Role
Rainer Oberbauer, MD, PhD	Medical University of Vienna	Principal Investigator

Locations

Facility	Status	City	State	ZIP	Country	Contacts
Medical university of Vienna	Recruiting	Vienna		1090	Austria

References Module

Citations

PubMed Identifier	Type	Citation	Retractions
34721420	Derived	Aschauer C, Jelencsics K, Hu K, Heinzel A, Gregorich MG, Vetter J, Schaller S, Winkler SM, Weinberger J, Pimenov L, Gualdoni GA, Eder M, Kainz A, Troescher AR, Regele H, Reindl-Schwaighofer R, Wekerle T, Huppa JB, Sykes M, Oberbauer R. Prospective Tracking of Donor-Reactive T-Cell Clones in the Circulation and Rejecting Human Kidney Allografts. Front Immunol. 2021 Oct 14;12:750005. doi: 10.3389/fimmu.2021.750005. eCollection 2021.
31477052

ID	Term
D012919	Social Behavior
D001519	Behavior

ID	Term
D006650	Histocompatibility Testing
D007159	Immunologic Tests
D019411	Clinical Laboratory Techniques
D019937	Diagnostic Techniques and Procedures