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

NCT07194057 | Not Yet Recruiting

• 1 other identifier: PI-6796
• Study Type: observational
• Target: 200
• Locations: 3 countries
• Sites: 4

Brief Summary

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).

Conditions

Transplant Complication; Kidney Transplant; Liver Transplant

Keywords

observational; epigenomic analysis; genomic analysis; european health data space

Outcome Measures

Primary Outcomes (16)

• Epstein Barr Infection

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

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

• Cytomegalovirus infection

  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)

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

• BK virus infection

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

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

• Cholangitis

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

  From transplant until end of post-transplant follow-up period

• Urinary Tract Infection

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

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

• Sepsis

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

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

• Renal Calcineurin Inhibitors toxicity

  Histological evidence of kidney CNI-related kidney damage

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

• Mycophenolate mofetil toxicity

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

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

• mTOR inhibitor toxicity

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

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

• Thrombotic microangiopathy

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

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

• Kidney rejection episode

  Histological evidence based on Banff criteria

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

• Liver rejection episode

  Histological evidence based on Banff criteria

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

• Chronic liver rejection

  Histological evidence based on Banff criteria

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

• Chronic kidney rejection

  Histological evidence based on Banff criteria

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

• Chronic renal failure after pLTx

  Elevation of serum-creatinine for 3\>months

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

• Chronic liver failure (graft chirrosis and fibrosis)

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

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

Secondary Outcomes (17)

• Liver Primary non-function

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

• Liver Primary non-function

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

• Liver Primary non-function

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

• Kidney primary non-function

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

• Liver early allograft dysfunction

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

Study Arms (2)

Paediatric kidney and liver transplant that suffered a clinical event of interest after transplant

This cohort is made up of paediatric kidney and liver patients that had a clinical event after transplantation. The main clinical events of interest of this study are: viral infections, bacterial infections, drug-related toxicity and rejection. All patients will undergo genomic and methylomic tests to diagnose biological risk factors that could help determine the risk of developing the clinical event of interest.

Genetic: Whole genome sequencing; Genetic: Polygenic Risk Score Calculation; Diagnostic Test: Methylome and episignatures

Paediatric kidney and liver transplant patients with no events after transplant

This cohort is made up of paediatric kidney and liver patients that did not develop a clinical event after transplantation. All patients will undergo genomic and methylomic tests. The genetic and methylomic results will be compared to those of the patients that developed a clinical event. The objetive is to identify biological risk factors that could help determine the risk of developing the clinical event of interest.

Genetic: Whole genome sequencing; Genetic: Polygenic Risk Score Calculation; Diagnostic Test: Methylome and episignatures

Interventions

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.

Also known as: Methylomic array, Polygenic risk score

Paediatric kidney and liver transplant patients with no events after transplant; Paediatric kidney and liver transplant that suffered a clinical event of interest after transplant

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).

Paediatric kidney and liver transplant patients with no events after transplant; Paediatric kidney and liver transplant that suffered a clinical event of interest after transplant

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.

Paediatric kidney and liver transplant patients with no events after transplant; Paediatric kidney and liver transplant that suffered a clinical event of interest after transplant

Eligibility Criteria

• Age: 6 Months - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

This study will enroll paediatric patients that have underdone a renal i liver transplant

You may qualify if:

• ● 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Instituto de Investigación Hospital Universitario La Paz: lead

Study Sites (4)

University Medical Center Hamburg-Eppendorf (UKE),

Hamburg, 20251, Germany

Location

Mediterranean Institute for Transplantation (ISMETT)

Palermo, Sicily, 90127, Italy

Location

University Hospital Padova

Padua, 35128, Italy

Location

Hospital Universitario La Paz

Madrid, Madrid, 28046, Spain

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood samples will be retained for extraction of DNA.

MeSH Terms

Interventions

Whole Genome Sequencing; Epigenome

Intervention Hierarchy (Ancestors)

Sequence Analysis, DNA; Sequence Analysis; Genetic Techniques; Investigative Techniques; Genome; Genetic Structures; Genetic Phenomena

Central Study Contacts

Paula Valle Simon, PhD

CONTACT

914975485; pvalle@salud.madrid.org

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: OTHER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2025
• First Posted: September 26, 2025
• Study Start: September 30, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2028
• Last Updated: September 26, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

ES (1); DE (1); IT (2)