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NCT Number: NCT07194057

"A Privacy-protecting Environment for Child Transplants Health Related and Genomic Data Integration in the European Reference Network"

Protect_Child_101 is an observational study to be performed in children that have undergone a liver or renal transplant.

The aim of this study is to analyse small variations in the genetic material (DNA) of transplanted children. The investigators will also study a type of chemical 'marks' called methylations, which do not change the DNA itself, but can affect how it functions. These marks can influence how certain diseases develop or how the body responds to transplantation.

Specifically, investigators seek to discover:

* Whether there are genetic or epigenetic (methylation) alterations that may explain why some children develop serious diseases that require transplantation. * If these alterations can help us predict possible complications after transplantation, such as organ rejection, infections, organ failure, cancer development.

Within this study, data from the child's medical history will be collected. The data to be collected are demographic data (gender, age, ethnicity), clinical data, personal and family history possibly related to his/her disease, course and evolution of the disease, and complementary and laboratory examinations collected from his/her clinical history.

The only non-routine tests to be performed will be the genomic and methylomic tests. Nevertheless, these determinations will be performed on samples obtained during the child's routine care. No extra intervention is planned as part of this study.

Samples and clinical data will be collected at different time points after transplantation. Schematically, collection is planned for months 0, 1, 3, 6, 12 and 24 post-transplant. In addition to these pre-established points, comprehensive data collection will be attempted when the child suffers a relevant clinical event, e.g. infection, treatment toxicity, organ rejection (post-transplant complication).

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Key information

Conditions

Transplant Complication Kidney Transplant Liver Transplant

Age range

6 month–18 year

Sex eligibility

All sexes

Study type

Observational

Primary location

University Medical Center Hamburg-Eppendorf (UKE),, Hamburg, Germany

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • ● Paediatric patients (6 months to 18 years old) with liver or kidney transplant.

Both patients with de novo transplantation or in follow-up can be included in the study.

  • For the retrospective cohort, only patients within the first 5 years after transplantation will be included.
  • Patients and/or parents agreeing to participate in the study and provide consent for the obtention of clinical data and samples for genomic and methylomic analysis and the use of the information according to the protocol.

Exclusion criteria

  • Patients that are not being followed up in the clinical site.
  • Subjects alternating between different clinical sites. Subjects/Tutors that don't understand the informed consent form.
  • Subject or their legally authorized representative does not sign the informed consent document.
  • Re-transplantation or AB0-incompatible transplantation.

Treatment and study plan

Whole Genome Sequencing

Genetic

Whole genome sequencing (WGS) is an advanced genomic technique that allows for the comprehensive analysis of an individual's entire DNA sequence, including both coding and non-coding regions. In the context of pediatric transplantation, WGS offers a powerful tool for uncovering underlying genetic disorders that may influence transplant eligibility, donor-recipient compatibility, immune response, or risk of post-transplant complications. It enables the identification of rare monogenic diseases, pharmacogenomic markers relevant to immunosuppressive therapy, and potential genetic predispositions to graft rejection or infection. Integrating WGS into transplant evaluation process enhances personalized medicine approaches, contributing to improved long-term outcomes in pediatric transplant recipients.

Other names: Methylomic array, Polygenic risk score

Polygenic Risk Score Calculation

Genetic

A polygenic risk score (PRS) calculation will be performed to quantitatively estimate the an individual's genetic predisposition to the original disease that led to transplantation. These scores are calculated by aggregating the weighted sum of risk alleles-most commonly single nucleotide polymorphisms (SNPs)-each of which contributes a small effect size as determined by genome-wide association studies (GWAS).

Methylome and episignatures

Diagnostic Test

Methylomic analysis in paediatric transplantation refers to the comprehensive profiling and study of DNA methylation patterns across the genome to understand epigenetic modifications associated with transplant-related outcomes.

This epigenetic approach enables the identification of differentially methylated regions (DMRs) that may correlate with clinical phenotypes, such as graft acceptance or rejection, infectious complications, or immune dysregulation.

The studies withjin the Protect_Child_101 project will be aimed at: 1) Refinement of episignatures, to increase specificity, sensitivity and robustness of those episignatures that already exist and 2) Discovery and validation of new disease, gene or variant specific mDNA signatures.

Primary outcomes

  1. Epstein Barr Infection

    Time frame: From transplant until end of post-transplant follow-up period (up to 7years)

    Number of Espstein Barr infections defined as >3500 copies in PCR in peripheral blood

  2. Cytomegalovirus infection

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    A) Primary CMV infection after transplant with or without CMV disease (>1000 copies/ml in peripheral blood in patients with previous negative CMV serology) B) Secondary CMV infection after transplant (any PCR with CMV disease or CMV >1000 copies/ml in asymptomatic patients)

  3. BK virus infection

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Positive BK viremia (define cut-off level) and/or histological evidence of BK nephropathy

  4. Cholangitis

    Time frame: From transplant until end of post-transplant follow-up period

    Worsening of liver function tests accompanied by an elevation in inflammatory markers, with or without a positive blood or bile culture.

  5. Urinary Tract Infection

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Positive urine cultures AND increased inflammation marker (e.g. CRP) or fever

  6. Sepsis

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    SIRS in relation to infectious cause +/- positive blood cultures

  7. Renal Calcineurin Inhibitors toxicity

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Histological evidence of kidney CNI-related kidney damage

  8. Mycophenolate mofetil toxicity

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Evidence of myelosuppression during therapy without any other proven cause and/or Clinical/histological evidence of MMF-related enteropathy

  9. mTOR inhibitor toxicity

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    mTOR induced-proteinuria (occurrence of proteinuria after mTOR exposure with resolution after treatment suspension)

  10. Thrombotic microangiopathy

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Ocurrence of no non immune-mediated hemolytic anemia and/or thrombocytopenia and/or hypertension and/or proteinuria with histological evidence of kidney TMA

  11. Kidney rejection episode

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Histological evidence based on Banff criteria

  12. Liver rejection episode

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Histological evidence based on Banff criteria

  13. Chronic liver rejection

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Histological evidence based on Banff criteria

  14. Chronic kidney rejection

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Histological evidence based on Banff criteria

  15. Chronic renal failure after pLTx

    Time frame: From transplant until end of post-transplant follow up period (up to 7 years)

    Elevation of serum-creatinine for 3>months

  16. Chronic liver failure (graft chirrosis and fibrosis)

    Time frame: From transplant until end of post-transplant follow up period (up to 7 years)

    Ocurrence of portal hypertension diagnosis both clinical (ascites, splenomegaly, varices) and analytical (thrombocytopenia) presentation.

Secondary outcomes

  1. Liver Primary non-function

    Time frame: From transplant to post-trasnplant follow-up period (up to 7 years)

    Requirement for immediate re-transplantation

  2. Liver Primary non-function

    Time frame: From transplant to post-transplant follow-up period (up to 7 years)

    Early death within the first 7 or 14 days following LT after exclusion of other identifiable causes of graft function such as vascular complications, rejection, or infection

  3. Liver Primary non-function

    Time frame: From transplant to post-trasnplant follow-up period (up to 7 years)

    Ocurrence of at least 2 of the following within 7 days post-transplant:

    • Alanine aminotransferase (ALT) greater than or equal to 2,000 U/L
    • INR greater than or equal to 10 mg/dl
    • Acidosis (Defined as one of the following: a) Arterial PH less or equal to 7,30. b) Venous pH less than or equal to 7,25. c) Lactate greater than or equal to 4 mmol/L)

  4. Kidney primary non-function

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Persistence of dialysis status or eGFR <15 ml/min/1.7 m2

  5. Liver early allograft dysfunction

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    One of the following laboratory criteria within the 7 first days post transplant:

    • Serum bilirubin ≥10 mg/dL (171 μmol/L) on day 7
    • INR ≥1.6 on day 7
    • AST or ALT >2000 IU/L within the first 7 days.

    Or, for 5 consecutive days after day 7:

    • Bilirubin > 10 mg/ dL
    • INR > 1.6
    • Serum Urea > 100 mg/dL

  6. Delayed kidney Graft Function

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Need for dialysis within the first 7 days after kidney transplantation

  7. Vascular Complications

    Time frame: From transplant until end of post-transplant follow-up period (Up to 7 years)

    Hepatic artery thrombosis (HAT) or portal vein stenosis (may lead to ischemic injury and chronic dysfunction)

  8. Biliary Complications

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Biliary structures, leaks, or ischemic cholangiopathy due to vascular insufficiency can cause chronic dysfunction.

  9. Urological complications

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Need of re-intervention due to post-surgical events

  10. Post-transplant lymphoproliferative disease

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Histological diagnosis of PTLD: histology, immunohistochemistry, EBV detection (EBER in situ hybridization), and clonality studies, classified according to WHO PTLD categories.

  11. Post-transplant lymphoproliferative disease

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Radiological diagnosis of PTLD: heterogeneous extranodal masses, allograft involvement, and CNS or visceral lesions.

  12. Diabetes

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    The diagnosis is confirmed when one of the following criteria is met on two separate occasions:

    Fasting plasma glucose (FPG): ≥126 mg/dL (7.0 mmol/L) after at least 8 hours fasting.

    Oral glucose tolerance test (OGTT): 2-hour plasma glucose ≥200 mg/dL (11.1 mmol/L) after a 75 g oral glucose load.

    Hemoglobin A1c (HbA1c): ≥6.5%, using a standardized assay.

    Random plasma glucose: ≥200 mg/dL (11.1 mmol/L) in the presence of classic symptoms of hyperglycemia (polyuria, polydipsia, weight loss).

  13. Posterior reversible encelopathy (PRES)

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Ocurrence of acute neurologic symptoms (headache, seizures, altered consciousness or visual disturbances) with typical neuroimaging (CT, MRI) findings (bilateral areas of white matter edema in the posterior cerebral hemispheres).

  14. Mortality

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Death by any cause

  15. Relapse of primary immune mediated disease

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    Ocurrence of nephrotic range proteinuria after kidney transplant (excluding other causes)

  16. Relapse of primary immune mediated disease

    Time frame: From transplant until end of post-transplant follow-up period (up to 7 years)

    histological findings of Focal segmental glomerulosclerosis (FSGS) in kidney biopsy in a patient with primary FSGS

  17. Graft survival

    Time frame: From transplant until end of post-transplant follow-up period (up 7 years)

    Time from transplant to the need for dialysis or entry onto the re- transplant list.

Study contacts

Contact information is provided by the study sponsor or research team.

Paula Valle Simon, PhD

CONTACT

[email protected]

914975485

Sponsors and collaborators

Lead sponsor

Instituto de Investigación Hospital Universitario La Paz

Other

Registry information

Acronym: Protect_Child

Important dates

Study start
2025
Primary completion
2028
Study completion
2028
First posted
Sep 26, 2025
Registry last updated
Sep 26, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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