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

Sponsor
Universitair Ziekenhuis Brussel
Study ID
NCT00798785
Phase
PHASE1/PHASE2
Status
Unknown

Conditions

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • ATG-MMF-TAC — DRUG
    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.
  • ATG-Rituximab-MMF-TAC — DRUG
    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.
  • ATG-basilixumab-MMF-TAC — DRUG
    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.
  • omentum — PROCEDURE
    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.

Study Details

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

Key Dates

Start date
Oct 31, 2006
Status verified
Dec 2013
Primary completion
Dec 31, 2014
Completion
Dec 31, 2014

Study Design

Enrollment
50 participants (estimated)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: group I ATG-MMF-TAC
    Two clinical implants in the liver: First implant: ATG-fresenium Maintained immunosuppression: MMF-TAC n=30
  • Experimental: group II ATG-Rituximab-MMF-TAC
    Two clinical implants in the liver: First Implant: ATG fresenium + Rituximab Maintained immunosuppression: MMF-TAC n=5
  • Experimental: group III ATG-Basilixumab-MMF-TAC
    Two clinical implants in the liver: First implant: ATG-fresenium Second implant: basilixumab Maintained immunosuppression: MMF-TAC n=5
  • Experimental: group IV omentum
    Two clinical implants: first in the omentum followed by a clinical implant in the liver: First implant: ATG-fresenium Maintained immunosuppression: MMF-TAC n=10

Primary Outcome Measure

Evidence of clinically relevant beta cell graft function [ Time Frame: up to 60 months ]

Central Contacts

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