The study is a phase 2, monocentric, open-label study. The investigators will recruit 12 patients with T1D to be randomly (1:1) assigned to receive islet either into the liver through the portal venous circulation (standard procedure; arm A, n=6) or directly into the omentum (arm B, n=6). Patients will be selected from those eligible for islet Tx based on local practice and guidelines. Immunosuppression will consist of five doses IV infusion of rabbit Anti-thymocyte Globulin (ATG, Thymoglobulin®), starting two days prior to the islet transplant. Maintenance mycophenolate mofetil (MMF) therapy (1-2 g/day as BID dosing) will be started on Day -1 pre-transplant. Tacrolimus will be administered orally twice daily on Day 1 post-transplant to maintain a trough level of 10-12 ng/mL for 3 months, then 6-10 ng/mL thereafter. Etanercept will be given IV before the islet transplant (50 mg), and then at 25 mg (subcutaneously) on POD +3, +7 and +10.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
12
This is a single procedure protocol. Only a single islet transplant will be performed in the patient. Islets can be isolated from more than one pancreas donor. The final islet product is a sterile suspension of ≥70% viable, ≥30% pure, allogeneic islets. A minimum of 5000 IEQ/KG will be transplanted. Although this study is a single dose protocol, islet transplant recipients with partial islet graft function will be considered for a second islet transplant (intra-hepatic administration) if they do not achieve primary efficacy endpoint criteria at 1 year
IRCCS San Raffaele Scientific Institute
Milan, Italy
A1c </= 6.5% and no severe hypoglycemia
composite outcome: Proportion of subjects with HbA1c ≤6.5% at 1 year AND free of severe hypoglycemic events from Day 28 to Day 365, inclusive, after the islet transplant.
Time frame: 1 year
Insulin requirements
the percent reduction in insulin requirements
Time frame: At 75±7, 365 ± 14 ,and 730 ± 14 days following the islet transplant
Insulin secretion
basal (fasting) and 90-min glucose and c-peptide derived from the mixed-meal tolerance test (MMTT)
Time frame: At 75±7, 365 ± 14 ,and 730 ± 14 days following the islet transplant
Glucose control
HbA1c
Time frame: At 75±7, 365 ± 14 ,and 730 ± 14 days following the islet transplant
Number of participants with treatment-related adverse events as assessed by CTCAE v4.0
incidence of post-transplant infections, malignancies, morbidity, and other AEs
Time frame: 1 year
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