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

Обзор

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).

Вмешательства

• Генная терапия Whole genome sequencing
  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, p
• Генная терапия Polygenic Risk Score Calculation
  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).
• Диагностический тест Methylome and episignatures
  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\

Первичные конечные точки

• Epstein Barr Infection [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7years)]
• Cytomegalovirus infection [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]
• BK virus infection [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]
• Cholangitis [Срок оценки: From transplant until end of post-transplant follow-up period]
• Urinary Tract Infection [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]
• Sepsis [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]
• Renal Calcineurin Inhibitors toxicity [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]
• Mycophenolate mofetil toxicity [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]
• mTOR inhibitor toxicity [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]
• Thrombotic microangiopathy [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]

Вторичные конечные точки (12)

• Liver Primary non-function [Срок оценки: From transplant to post-trasnplant follow-up period (up to 7 years)]
• Liver Primary non-function [Срок оценки: From transplant to post-transplant follow-up period (up to 7 years)]
• Liver Primary non-function [Срок оценки: From transplant to post-trasnplant follow-up period (up to 7 years)]
• Kidney primary non-function [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]
• Liver early allograft dysfunction [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]
• Delayed kidney Graft Function [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]
• Vascular Complications [Срок оценки: From transplant until end of post-transplant follow-up period (Up to 7 years)]
• Biliary Complications [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]
• Urological complications [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]
• Post-transplant lymphoproliferative disease [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]
• Post-transplant lymphoproliferative disease [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]
• Diabetes [Срок оценки: From transplant until end of post-transplant follow-up period (up to 7 years)]

Критерии участия

Критерии включения

• ● 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.

Критерии исключения

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Модель наблюдения

Когортное

Центры проведения

Италия · 2 центра

• Mediterranean Institute for Transplantation (ISMETT) — Palermo
• University Hospital Padova — Padova

Германия · 1 центр

• University Medical Center Hamburg-Eppendorf (UKE), — Hamburg

Испания · 1 центр

• Hospital Universitario La Paz — Madrid

Идентификаторы

NCT: NCT07194057 · PI-6796

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗