NCT00798785

Long-term Function of Beta Cell Allografts in Non-uremic Type 1 Diabetic Patients

• Status: Unknown
• Phase: Phase 1 / Phase 2
• Study type: Interventional
• Enrollment: 50 (estimated)
• Sponsor: Universitair Ziekenhuis Brussel · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

Summary

The present proof of concept study addresses the following specific aims: The general objectives of this work are: 1. To increase and maintain the functional beta-cell mass after islet transplantation under a condition of low-dose tacrolimus 2. To co-investigate the potential of alternative sites for encapsulated beta-cells

Detailed description

1. Aim 1: To increase functional beta cell mass by adding rituximab at first implantation 2. Aim 2: To increase functional beta cell mass by adding basilixumab at second implantation 3. Aim 3: To assess the influence of down-tapering the tacrolimus dose during posttransplant years 2-5 on these data, on metabolic control, on the prevalence of hypoglycemia and on safety parameters. 4. Aim 4: To investigate the potential of the peritoneum and omentum as an alternative site for encapsulated beta-cells. 5. Aim 5: To investigate the potential of the brachioradial muscle as an alternative site for encapsulated beta-cells.

Conditions

• Diabetes Mellitus, Type 1

Interventions

Type	Name	Description
DRUG	ATG-MMF-TAC	ATG-fresenium for max 6 consecutive days depending on CD3 count, starting the day before transplantation. Tacrolimus levels for 2 years between 8-10 ng/ml. At year 2: randomization: group A: till 48 months: tacrolimus levels 8-10 ng/ml 48-60 months: tacrolimus levels 6-8 ng/ml group B: 24-36 months: 6-8 ng/ml 36-60 months: 4-6 ng/ml A subgroup of these patients will receive a sub clinical implant subcutaneous (total n=5) at the time of the first clinical implant in the liver.
DRUG	ATG-Rituximab-MMF-TAC	ATG-fresenium for max 6 consecutive days depending on CD3 count, starting the day before transplantation. Rituximab: the day before transplantation, day 5; 12 and 19 after implantation. Tacrolimus levels for 2 years between 8-10 ng/ml. At year 2: randomization: group A: till 48 months: tacrolimus levels 8-10 ng/ml 48-60 months: tacrolimus levels 6-8 ng/ml group B: 24-36 months: 6-8 ng/ml 36-60 months: 4-6 ng/ml A subgroup of these patients will receive a sub clinical implant, subcutaneous at the time of the first clinical implant in the liver.
DRUG	ATG-basilixumab-MMF-TAC	First transplantation: ATG-fresenium for max 6 consecutive days depending on CD3 count, starting the day before transplantation. Second transplantation: Basilixumab: the day before the second transplantation followed by 4days after transplantation. Tacrolimus levels for 2 years between 8-10 ng/ml. At year 2: randomization: group A: till 48 months: tacrolimus levels 8-10 ng/ml 48-60 months: tacrolimus levels 6-8 ng/ml group B: 24-36 months: 6-8 ng/ml 36-60 months: 4-6 ng/ml A subgroup of these patients will receive a sub clinical implant, subcutaneous at the time of the first clinical implant in the liver.
PROCEDURE	omentum	Two clinical implants: first in omentum followed by a clinical implant in the liver: In a group of 10 patients, a clinical implant in the omentum will be implanted. If random C-peptide levels \>= 0.5 ng/ml are measured at 2 months post-transplantation, a second omental implant will be done. If no clinical relevant beta cell graft function is measured, two intraportal implants will be given as a compassionate use procedure. An interim analysis after 5 patients has to shown clinical relevant function at month 2 in 3 out of 5 patients before the subsequent 5 patients can be transplanted in the omentum.

Timeline

• Start date: 2006-10-01
• Primary completion: 2014-12-01
• Completion: 2014-12-01
• First posted: 2008-11-26
• Last updated: 2013-12-30

Locations

4 sites across 1 country: Belgium