Renal Transplant RejectionALL-T-COPIESNCT03422224
ALLoreactive T-Cell receptOr RePertoire in kidnEy tranSplantation
An observational study of Renal Transplant Rejection and Immune Repertoire, run by Medical University of Vienna at 1 site in Austria.
Trial 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: 1. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Renal Transplant Rejection, Immune Repertoire, Transplant; Complication, Rejection
- What is being tested?
- Mixed lymphocyte reaction
- How many people
- 50 participants
- Where
- 1 siteAustria
- Study dates
- 1 Jul 2017to Jul 2024
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Chronic kidney disease
Who may be able to join
- Kidney transplantation in our center
Who cannot join
- Donor not evaluated by our center
Trial locations and contacts
1 site in 1 country.
Austria1 site, 1 recruiting
- Recruiting
Medical university of Vienna
Vienna, 1090
Constantin N Aschauer, MD, 00434040043890, constantin.aschauer@meduniwien.ac.at
About this study
Official title: Alloreactive t Cell Repertoire in Kidney Transplantation Recipients
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.
Read the 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.
- Conditions
- Renal Transplant Rejection, Immune Repertoire, Transplant; Complication, Rejection, Alloreactivity
- Being tested
- Mixed lymphocyte reaction
- Medical subject headings
- Rejection, Psychology
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Mixed lymphocyte reactionDiagnostic test
Assessment of alloreactive T cell repertoire
| Study group | Role | What they receive |
|---|---|---|
| Good transplant function | Kidney transplant recipients without histological signs of rejection. Receives: Diagnostic Test: Mixed lymphocyte reaction | |
| Transplant Rejection | Kidney transplant recipinets experiencing a T cell mediated rejection episode. Receives: Diagnostic Test: Mixed lymphocyte reaction |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rejection
biopsy proven rejection
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2018
- Study start1 Jul 2017
- Primary completionJul 2024 (estimated)
- Study completionJul 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Renal Transplant RejectionStudies of the same condition, open and under way.
- More trials run by Medical University of ViennaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Medical University of Vienna
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Rainer Oberbauer, Medical University of Vienna
- Investigators
- Rainer Oberbauer, MD, PhD, Principal investigator, Medical University of Vienna
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03422224
- Sponsor's protocol ID
- ALL-T-COPIES
- Acronym
- ALL-T-COPIES
- Status last verified
- Oct 2023
- First submitted
- 30 Jan 2018
- Last updated
- 23 Oct 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 34721420Aschauer C, Jelencsics K, Hu K, Heinzel A, Vetter J, Fraunhofer T, Schaller S, Winkler S, Pimenov L, Gualdoni GA, Eder M, Kainz A, Regele H, Reindl-Schwaighofer R, Oberbauer R. Next generation sequencing based assessment of the alloreactive T cell receptor repertoire in kidney transplant patients during rejection: a prospective cohort study. BMC Nephrol. 2019 Sep 2;20(1):346. doi: 10.1186/s12882-019-1541-5.
PubMed 31477052
Study at a glance
From the registry record, last updated by the sponsor on 23 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Alloreactive t Cell Repertoire in Kidney Transplantation Recipients
- ClinicalTrials.gov ID
- NCT03422224
- Acronym / sponsor ID
- ALL-T-COPIES / ALL-T-COPIES
- Conditions
- Renal Transplant Rejection, Immune Repertoire, Transplant; Complication, Rejection, Alloreactivity
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Medical University of ViennaUniversity, hospital or other
- Study start
- 1 Jul 2017 (actual)
- Primary completion
- Jul 2024 (estimated)
- Study completion
- Jul 2024 (estimated)
- First posted
- 5 Feb 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Good transplant function | – | Diagnostic Test: Mixed lymphocyte reactionKidney transplant recipients without histological signs of rejection. |
| Transplant Rejection | – | Diagnostic Test: Mixed lymphocyte reactionKidney transplant recipinets experiencing a T cell mediated rejection episode. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Chronic kidney disease
Key inclusion criteria (1 listed)
- Kidney transplantation in our center
Key exclusion criteria (1 listed)
- Donor not evaluated by our center
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mixed lymphocyte reactionAssessment of alloreactive T cell repertoire | Diagnostic test | Good transplant function, Transplant Rejection |
Primary outcome
Rejection
Time frame: 12 months
biopsy proven rejection
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Oct 2023.
- Derived from this study: PubMed 34721420Aschauer 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.
- Derived from this study: PubMed 31477052Aschauer C, Jelencsics K, Hu K, Heinzel A, Vetter J, Fraunhofer T, Schaller S, Winkler S, Pimenov L, Gualdoni GA, Eder M, Kainz A, Regele H, Reindl-Schwaighofer R, Oberbauer R. Next generation sequencing based assessment of the alloreactive T cell receptor repertoire in kidney transplant patients during rejection: a prospective cohort study. BMC Nephrol. 2019 Sep 2;20(1):346. doi: 10.1186/s12882-019-1541-5.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rainer Oberbauer, MD, PhD principal investigator
Medical University of Vienna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Renal Transplant Rejection and Immune Repertoire, run by Medical University of Vienna at 1 site in Austria.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 23 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Austria. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Constantin N Aschauer, MD (00434040043890, constantin.aschauer@meduniwien.ac.at), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rejection (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03422224, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Oct 2023.