Leuven Tolerogenic Protocol for Intestinal Transplantation

Organ Transplantation Clinical Trial

— LP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02314949
• Other study ID #: LPs56862
• Status: Recruiting
• Phase: N/A
• First received: November 26, 2014
• Last updated: December 8, 2014
• Start date: October 2000

Study information

• Verified date: July 2013
• Source: Universitaire Ziekenhuizen Leuven
• Contact: Jacques Pirenne, MD,PhD,MsC
• Phone: +32 16 34 87 27
• Email: jacques.pirenne[@]uzleuven.be
• Is FDA regulated: No
• Health authority: Belgium: Federal Agency for Medicinal Products and Health Products
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 13
• Est. primary completion date: January 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• all patients awaiting intestinal transplantation

Exclusion Criteria:

• living donation

Study Design

Observational Model: Cohort, Time Perspective: Retrospective

Related Conditions & MeSH terms

• Intestine
• Organ Transplantation

Intervention

Procedure:
• intestinal transplantation

Locations

Country	Name	City	State
Belgium	UZ Leuven	Leuven

Sponsors (1)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen Leuven

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Survival	routine clinical follow-up and Kaplan Meier Analysis	10 years	No
Secondary	T-regulatory cells CD4+ CD45RA- Foxp3hi	Peripheral blood mononuclear cells (PBMC's) isolation and flow cytometry	10 years	No
Secondary	rejection	routine endoscopical obtained ileal biopsies analysed for number of apoptotic bodies in the crypt	10 years	No