Pre Transplant Rapamycin Treatment in Islet Transplantation Alone

Phase 3

Completed

• Conditions: Diabetes Mellitus, Type 1
• Interventions: Drug: rapamycin

• Registration Number: NCT01060605
• Lead Sponsor: IRCCS San Raffaele

Brief Summary

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.

Detailed 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.

Study Timeline

• Study Start: 2001-10
• Primary Completion: 2005-12
• Study Completion: 2009-09
• Status Verified: 2010-01
• Study First Submitted: 2010-02-01
• Study First Submitted QC: 2010-02-01
• Last Update Submitted: 2010-02-01
• Study First Posted: 2010-02-02
• Last Update Posted: 2010-02-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 11

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Rapamycin pre transplant	rapamycin	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).

Primary Outcome Measures

Name	Time	Method
Evidence of insulin independence with adequate control of blood glucose (<140 mg/mL fasting; < 180 mg/mL post prandial, after the final infusion	1 year

Secondary Outcome Measures

Name	Time	Method
basal and stimulated C-peptide levels	weekly within 1st month; monthly for 1 year
glycated haemoglobin	monthly
rapamycin and tacrolimus trough levels	every week for the first month, and monthly thereafter
renal and liver function, white blood cells count, total lymphocytes and lymphocytes subpopulations (CD24, CD19), hemoglobin, fibrinogen (FG), cross-linked fibrin degradation products, C-reactive protein (CRP)	every week for the first month, and monthly thereafter

Trial Locations

Locations (1)

Transplant Unit, IRCCS San Raffaele; 🇮🇹 Milano, Italy