Leuven Tolerogenic Protocol for Intestinal Transplantation (LP)

A Multifactorial Immunomodulatory Protocol -Promoting T-regulatory Cells- Prolongs Graft and Patient Survival After Intestinal Transplantation

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.

Study Overview

• Status: Recruiting
• Conditions: Organ Transplantation; Intestine
• Intervention / Treatment: Procedure: intestinal transplantation

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.

• Study Type: Observational
• Enrollment (Estimated): 13

Contacts and Locations

• Study Contact: Name: Jacques Pirenne, MD,PhD,MsC; Phone Number: +32 16 34 87 27; Email: jacques.pirenne@uzleuven.be
• Study Contact Backup: Name: Laurens J Ceulemans, MD; Phone Number: +32 16 34 15 45; Email: laurens.ceulemans@uzleuven.be

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • Recruiting
    • UZ Leuven
    • Contact: Sarah Mertens; Phone Number: +32 16 34 29 61; Email: sarah.mertens@uzleuven.be

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

All patients who underwent intestinal transplantation

Description

Inclusion Criteria:

• all patients awaiting intestinal transplantation

Exclusion Criteria:

• living donation

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
intestinal transplantation; all performed intestinal transplants underwent the same Leuven intestinal transplant protocol	Procedure: intestinal transplantation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Survival	routine clinical follow-up and Kaplan Meier Analysis	10 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
T-regulatory cells CD4+ CD45RA- Foxp3hi	Peripheral blood mononuclear cells (PBMC's) isolation and flow cytometry	10 years
rejection	routine endoscopical obtained ileal biopsies analysed for number of apoptotic bodies in the crypt	10 years

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2000
• Primary Completion (Estimated): January 1, 2025
• Study Completion (Estimated): January 1, 2025

Study Registration Dates

• First Submitted: November 26, 2014
• First Submitted That Met QC Criteria: December 8, 2014
• First Posted (Estimated): December 11, 2014

Study Record Updates

• Last Update Posted (Actual): July 15, 2024
• Last Update Submitted That Met QC Criteria: July 12, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: immunomodulation; Tolerogenic protocol; T-regulatory cells
• Other Study ID Numbers: LPs56862