Pre Transplant Rapamycin Treatment in Islet Transplantation Alone (ITA-Rp)

San Donato Group (GSD)

Status and phase: Completed; Phase 3

Conditions: Diabetes Mellitus, Type 1

Treatments: Drug: rapamycin

Study type: Interventional

Funder types: Other

Identifiers

NCT01060605

emendament 2001 to C99B901251

Details and patient eligibility

About

Numerous changes to the original Edmonton protocol have been proposed in the attempt of improving the still unsatisfactory long-term function of ITA. Rapamycin may blunt the early inflammatory response to islet transplantation in the liver, thus favoring islet engraftment.

Aim of the investigators study was to evaluate the effect of a pre-transplant treatment with rapamycin in patients with type 1 diabetes receiving islet transplant alone and immunosuppression according to the Edmonton protocol.

Full description

Pre-transplant rapamycin is administered for at least four weeks prior to the first islet infusion at the dose of 0.1 mg/kg (target trough levels: 8-10 ng/mL). During the pre-transplant rapamycin treatment rapamycin trough levels, renal and liver function, white blood cells count, total lymphocytes and lymphocytes subpopulations, hemoglobin, fibrinogen, cross-linked fibrin degradation products, C-reactive protein, exogenous insulin requirement every week for the first month, and monthly thereafter are measured. Induction and maintenance immunosuppressive regimen after each islet infusion is administered according to the Edmonton protocol (daclizumab, rapamycin, target trough levels: 12-15 ng/mL during the first 3 months and 10-12 ng/mL thereafter and tacrolimus 2 mg/day,target trough levels: 4-6 ng/mL). Islets are infused into the liver through the portal vein under local anesthesia Portography is performed before and after infusion. The islet function is evaluated measuring fasting C-pep, EIR, and HbA1c, immediately before the first islet infusion and subsequently every day for the first week, and then weekly for the first month ; every month after the last islet infusion for the first year and every 6 month thereafter.

Enrollment: 11 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• type 1 diabetes
• ≥5 years of type 1 diabetes
• hypoglycaemia unawareness
• progression of chronic complications of diabetes despite intensive insulin regimen

Exclusion criteria

• overt kidney disease
• chronic liver disease
• hepatic haemangioma
• severe cardiomyopathy
• untreated coronary artery disease

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Single Group Assignment

Masking: None (Open label)

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11 participants in 1 patient group

Rapamycin pre transplant

Experimental group

Description:

Pre-transplant rapamycin is administered for at least four weeks prior to the first islet infusion at the dose of 0.1 mg/kg (target trough levels: 8-10 ng/mL).

Treatment:

Drug: rapamycin