Pilot study to identify biomarkers for tolerance to liver grafts

Pilot study to identify biomarkers for tolerance to liver grafts - BIOTOL

Status

Recruiting

Phases

Unknown

Study type

Observational

Source

NL-OMON

Registry ID

NL-OMON47529

Enrollment

Registered

2014-08-08

Start date

2014-10-02

Completion date

Unknown

Last updated

2024-04-23

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

liver grafts

Interventions

None listed

Eligibility

Age

18 Years to 99 Years

Inclusion criteria

Inclusion criteria: Case control study: The experimental group consists of 8 LTx patients in Erasmus MC that are currently at least 6 months free of IS. 5 additional patients are currently in the process of IS reduction, and will be included as soon as they are 6 months free of IS. As a control group we will include 39 LTx patients matched with the experimental group for LTx-indication and time after LTx and have been continuously treated with IS., Cohort study: LTx-recipients in Erasmus MC in which for clinical reasons IS will be gradually withdrawn. Our estimation is that we can include 25 patients during the next 4 years, but this is fully dependent on clinical need to reduce and finally stop IS.

Exclusion criteria

Exclusion criteria: Severe recurrence of primary liver disease with development of cirrhosis.

Design outcomes

Primary

Measure	Time frame
Frequencies of donor-specific CD4+ Teff, CD4+Foxp3+ Treg, and CD4+CD49b+LAG-3+ Treg will be expressed as percentages of CD4+ T-cells. Frequencies of donor-specific CD8+ Teff will be expressed as percentages of CD8+ T-cells. The same calculations will be made for frequencies of T cells responding to 3rd party allo-antigen. A single cell RNA profile for tolerance will be established, as well as a functional immune response and TSDR methylation of immune cells within tolerant and control LTx recipients. In the case-control study frequencies of donor-specific T cells and 3rd-party specific T cells will be compared between tolerant patients and patients using IS, using the Mann-Whitney test or, if the variables are normally distributed, using the Wilcoxon test for unpaired samples. In the cohort study at each time point frequencies of donor-specific T cells and 3rd-party specific T cells will be compared between patients that do not reject during or after IS withdrawal and patients that do reject, using the same statistical tests.	—

Measure

Time frame

Frequencies of donor-specific CD4+ Teff, CD4+Foxp3+ Treg, and CD4+CD49b+LAG-3+ Treg will be expressed as percentages of CD4+ T-cells. Frequencies of donor-specific CD8+ Teff will be expressed as percentages of CD8+ T-cells. The same calculations will be made for frequencies of T cells responding to 3rd party allo-antigen. A single cell RNA profile for tolerance will be established, as well as a functional immune response and TSDR methylation of immune cells within tolerant and control LTx recipients. In the case-control study frequencies of donor-specific T cells and 3rd-party specific T cells will be compared between tolerant patients and patients using IS, using the Mann-Whitney test or, if the variables are normally distributed, using the Wilcoxon test for unpaired samples. In the cohort study at each time point frequencies of donor-specific T cells and 3rd-party specific T cells will be compared between patients that do not reject during or after IS withdrawal and patients that do reject, using the same statistical tests.

—

Secondary

Measure	Time frame
In tolerant patients only: degree of liver fibrosis (in kPa) as detected by fibroscan and by a combination of serum markers e.g. PINP, PIINP, TIMP, MMP	—

Countries

Netherlands

Outcome results