International (Pediatric) Peritoneal Biobank

Healthy Clinical Trial

Official title:

International (Pediatric) Peritoneal Biobank

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01893710
• Other study ID #: IPPB Biobank
• Secondary ID: University of He
• Status: Recruiting
• Start date: February 2011
• Est. completion date: December 2028

Study information

• Verified date: December 2023
• Source: Heidelberg University
• Contact: Claus P Schmitt, Prof
• Phone: +49 6221 56
• Email: claus.peter.schmitt[@]med.uni-heidelberg.de
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

Within few years the peritoneal membrane of adult peritoneal dialysis (PD) patients undergoes substantial morphological transformation, including progressive fibrosis, vasculopathy and neoangiogenesis. Ultrafiltration capacity steadily declines and ultimately results in PD failure. In children, peritoneal biopsies demonstrating PD associated alterations have not yet been obtained. They, however, should be particularly informative, since secondary tissue and vascular pathology related to ageing or diabetes is absent.

An international, prospective peritoneal membrane biopsy study in children on PD will therefore be performed. Biopsies will be obtained at time of PD catheter insertion, on occasion of intercurrent abdominal surgery (e.g. hernia repair, catheter exchange) and at time of renal transplantation. Quantitative histomorphometry and tissue protein expression analyses will be correlated with time integrated PD treatment modalities and functional characteristics as well as inflammatory and cardiovascular comorbidity surrogate parameter. Blood will be obtained during clinical routine sampling. Biopsies will be obtained during clinically indicated operations, without substantially increasing operation time and associated surgical risks. The detailed histomorphometry of the PD membrane will give additional information, potentially impacting on the individual PD regime.

3/2018: The analyses of the pediatric PD biopsy demonstrated early and major transformation of the peritoneal membrane with neutral pH low GDP fluids, and significant vasculopathy already in children with CKD stage 5, further progressing with PD. The underlying mechanisms are partly understood, only. In view of these major findings and the numerous open questions, collection of biosamples will be continued in children and also in adult PD patients. The following questions will be addressed: Molecular counterparts of peritoneal semi-permeability, solute and water transport (beyond AQP1), pathomechanisms and molecular and functional impact of peritoneal transformation with low and high GDP fluids, and the respective pathomechanisms and molecular and functional impact of vascular disease in CKD and with different PD fluids. The impact of renal transplantation following PD will be assessed in a subgroup of patients with tenckhoff catheter removal several weeks after transplantation and a functioning graft.

Description:

Please see study protocol and

http://www.pedpd.org

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 500
• Est. completion date: December 2028
• Est. primary completion date: October 2028
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 1 Day to 90 Years

Eligibility

Inclusion Criteria

• Age 0 to 90 years

• CKD 5D, peritoneal dialysis and

• Patients with normal renal function and elective abdominal surgery due to limited abdominal pathology (such as hernia repair, gallstones….)

• Patients post PD and post Tx

• Oral and written consent

• Ability to consent of the adult patient and of the parents and legal guardian of patients not yet of legal age, respectively

Exclusion Criteria:

• Abdominal adhesions, malformation and inflammation beyond PD induced changes

• Patients with disseminated tumour disease

• Patients with critical heart failure and other medical conditions, where the additional procedure may confer an increased increase risk

• Pregnancy

• Preterm babies (below 37 weeks of gestational age)

• Serum hemoglobin < 10 g/dl in newborns and < 8 g/dl in children and adults

Related Conditions & MeSH terms

• Healthy
• Kidney Failure, Chronic
• Peritoneal Dialysis Complication
• Renal Insufficiency
• Transplantation

Intervention

Procedure:
• biopsy sampling
Two parietal peritoneal samples, each 1 cm² x 0.3 cm in depth and three omental tissue samples, each 1 cm² in size will be obtained. Biopsy sampling will be performed in all groups. This is an observational not an interventional trial.

Locations

Country	Name	City	State
Austria	Department of Pediatrics, Medical University Vienna	Vienna
Belgium	UZ Ghent	Ghent
Czechia	University Children's Hospital	Prague
France	Service de Néphrologie Pédiatrique, Hôpital Femme Mere Enfant	Lyon
France	University Children's Hospital	Strasbourg
Germany	University Children's Hospital	Berlin
Germany	University Children's Hospital	Cologne
Germany	University Children's Hospital	Essen
Germany	UKE, University Children´s Hospital	Hamburg
Germany	Department of Medicine I (Nephrology), University of Heidelberg	Heidelberg	BW
Germany	KfH Pediatric Kidney Center, Department of Pediatric Nephrology, University of Marburg	Marburg
Hungary	University Children's Hospital	Budapest
Italy	University Children'Hospital	Genova
Italy	University Children's Hospital	Milano
Italy	Pediatric Nephrology, Dialysis and Transplant Unit	Padova
Lithuania	University children's Hospital	Vilnius
Malaysia	Paediatric CAPD unit, Kuala Lumpur Hospital	Kuala Lumpur
Poland	Krakow, Jagiellonian University Medical College	Krakow
Spain	Hospital Universitario Materno-Infantil Vall d' Hebron	Barcelona
Sweden	Karolinska University Hospital	Stockholm
Switzerland	Children's Hospital, Inselspital, Bern University Hospital and University of Bern	Bern
Turkey	University Children's Hospital	Adana
Turkey	Cerrahpasa School of Medicine	Istanbul
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Children's Mercy Hospital	Kansas City	Missouri
United States	The Children´s Hospital of Philadelphia	Narberth	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Heidelberg University

Countries where clinical trial is conducted

United States,  Austria,  Belgium,  Czechia,  France,  Germany,  Hungary,  Italy,  Lithuania,  Malaysia,  Poland,  Spain,  Sweden,  Switzerland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Submesothelial thickness (µm)	Digital imaging analysis of submesothelial thickness as a marker of peritoneal fibrosis (distance between mesothelium and adjacent muscle/adipos tissue)	2 years (average PD duration)
Other	Submesothelial lymphocyte, macrophage, MMT cell count	Quantification of peritoneal leucocyte Infiltration, i.e. number of CD45 positive lymphocytes and CD68 positive macrophages per mm² of submesothelial section area . The number of cells that underwent mesothelial-mesenchymal transition per mm² submesothelial section are quantified by immunohistochemical co-staining of mesothelial and fibroblast marker (cytokeratin and FSP1).	2 years (mean PD duration)
Other	Peritoneal VEGF and pSMAD abundance	Key cytokines involved in peritoneal membrane transformation will be measured immunohistochemically. These are VEGF and TGF-beta induced p-SMAD (%positive area per section area analysed).	2 years (mean PD duration)
Primary	Peritoneal vasculopathy (lumen vessel ratio)	Digital quantification of degree of vasculopathy, i.e the lumen vessel ratio. Healthy children have a L/V ratio of about 0.7. lower values represent vasculopathy with lumen narrowing, 0 is complete obliteration of the vessel.; This measurements will be accompanied by molecular analysis of pathomechanisms (including omics Technology)	Two years (Mean PD treatment time)
Secondary	Number of vessels per peritoneal membrane area (per mm²)	Digital histomorphometry of small vessel density per mm² submesothelial section area analysed.	at time of catheter insertion, intercurrent abdominal surgery and at time of renal transplantation

External Links

•   International Pediatric Peritoneal Dialysis Network