Leuven Tolerogenic Protocol for Intestinal Transplantation

NCT ID: NCT02314949

Last Updated: 2024-07-15

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 13 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2000-10-31
• Study Completion Date: 2025-01-31

Brief Summary

An immunomodulatory protocol, experimentally-proven to promote T-regulatory dependent graft protective mechanisms was applied in a clinical cohort of 13 intestinal transplant recipients to activate - in a protolerogenic environment - T-regulatory cells.

This protocol is the standard of care in the investigators intestinal transplant programme since the first intestinal transplant was performed in october 2000.

Detailed Description

The LP is a 4-step approach that aims to upregulate T-regulatory cells (T-Regs) by directly stimulating their development and removing stimuli that could suppress them, eventually creating an environment favorable for graft acceptance. This protocol has been based upon preclinical research perormfed in the investigators lab and has been implemented as standard of care since the inception of the clinical programma in 2000. Patients gave informed consent for Donor Specific Blood Transfusion. Ethical approval for collection of additional blood samples was granted by the local ethical committee (s56862).

Step 1. Donor-specific blood transfusion (DSBT). 400 mL of whole blood was collected from the donor at the time of procurement and was transfused systemically in the recipient prior to reperfusion.

Step 2. Avoiding high-dose steroids. After Intestinal Transplantation, only 16 mg of medrol was administered and tapered towards 4 mg in 3 to 6 months post-Tx, similar to the liver Tx protocol.

Step 3. Avoiding high-dose calcineurin inhibitors (tacrolimus). Initial levels of 15 ng/ml were tapered -within 3 to 6 months- to 5 ng/mL or less for liver-containing grafts and 6 to 8 ng/mL for isolated intestinal grafts.

Step 4. Maintaining mucosal integrity and reducing ischemia reperfusion injury, inflammation, and endotoxin translocation. This was obtained by selecting perfect (ischemia-free) donors (<50y, absence of significant hypotension, vasopressor requirement and cardiac arrest); pretreating donors with selective bowel decontamination and glutamine; gentle manipulations of the organs during donor and recipient surgery; aiming for short cold and warm ischemic times (5h and 30' respectively). Bowel decontamination consists of Nilstat, Tobramycine and Colimycine administered by a nasogastric tube and continued posttransplant during three months. Glutamine is supplemented parenterally (Dipeptiven Kabi Fresenius) and enterally (Alitracq) to donors and continued posttransplant.

Conditions

Organ Transplantation; Intestine

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: RETROSPECTIVE

Study Groups

intestinal transplantation

all performed intestinal transplants underwent the same Leuven intestinal transplant protocol

intestinal transplantation

Intervention Type: PROCEDURE

Interventions

intestinal transplantation

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

• all patients awaiting intestinal transplantation

Exclusion Criteria

• living donation

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

UZ Leuven

Leuven, , Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Jacques Pirenne, MD,PhD,MsC

Role: CONTACT

jacques.pirenne@uzleuven.be

+32 16 34 87 27

Laurens J Ceulemans, MD

Role: CONTACT

laurens.ceulemans@uzleuven.be

+32 16 34 15 45

Facility Contacts

Sarah Mertens

Role: primary

sarah.mertens@uzleuven.be

+32 16 34 29 61

References

Ceulemans LJ, Braza F, Monbaliu D, Jochmans I, De Hertogh G, Du Plessis J, Emonds MP, Kitade H, Kawai M, Li Y, Zhao X, Koshiba T, Sprangers B, Brouard S, Waer M, Pirenne J. The Leuven Immunomodulatory Protocol Promotes T-Regulatory Cells and Substantially Prolongs Survival After First Intestinal Transplantation. Am J Transplant. 2016 Oct;16(10):2973-2985. doi: 10.1111/ajt.13815. Epub 2016 May 12.

Reference Type: DERIVED

PMID: 27037650 (View on PubMed)

Other Identifiers

LPs56862

Identifier Type: -

Identifier Source: org_study_id