"A Privacy-protecting Environment for Child Transplants Health Related and Genomic Data Integration in the European Reference Network"
Trial Snapshot
- Phase
- Not Applicable
- Status
- Not yet recruiting
- Enrollment
- 200
- Locations
- 4
- Primary Endpoint
- Epstein Barr Infection
Study Overview
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).
Study Design
- Study Type
- Observational
- Observational Model
- Cohort
- Time Perspective
- Other
Eligibility Criteria
- Ages
- 6 Months to 18 Years (Child, Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Outcomes
Primary Outcomes
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
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)
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
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.
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
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
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
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
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)
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
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
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
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
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
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
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
- 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))
- Delayed kidney Graft Function(From transplant until end of post-transplant follow-up period (up to 7 years))
- Vascular Complications(From transplant until end of post-transplant follow-up period (Up to 7 years))
- Biliary Complications(From transplant until end of post-transplant follow-up period (up to 7 years))
- Urological complications(From transplant until end of post-transplant follow-up period (up to 7 years))
- Post-transplant lymphoproliferative disease(From transplant until end of post-transplant follow-up period (up to 7 years))
- Diabetes(From transplant until end of post-transplant follow-up period (up to 7 years))
- Posterior reversible encelopathy (PRES)(From transplant until end of post-transplant follow-up period (up to 7 years))
- Mortality(From transplant until end of post-transplant follow-up period (up to 7 years))
- Relapse of primary immune mediated disease(From transplant until end of post-transplant follow-up period (up to 7 years))
- Graft survival(From transplant until end of post-transplant follow-up period (up 7 years))