Pre Transplant Rapamycin Treatment in Islet Transplantation Alone

Diabetes Mellitus, Type 1 Clinical Trial

— ITA-Rp  

Official title:

Effects of Pre-transplant Rapamycin Treatment and Tacrolimus Levels on the Outcome of Islet Transplantation Alone in Patients Receiving Edmonton Protocol.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01060605
• Other study ID #: emendament 2001 to C99B901251
• Status: Completed
• Phase: Phase 3
• First received: February 1, 2010
• Last updated: February 1, 2010
• Start date: October 2001
• Est. completion date: September 2009

Study information

• Verified date: January 2010
• Source: IRCCS San Raffaele
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 11
• Est. completion date: September 2009
• Est. primary completion date: December 2005
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus, Type 1

Intervention

Drug:
• 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).

Locations

Country	Name	City	State
Italy	Transplant Unit, IRCCS San Raffaele	Milano

Sponsors (4)

Lead Sponsor	Collaborator
IRCCS San Raffaele	Juvenile Diabetes Research Foundation, Ministry of Education, Universities and Research, Italy, Telethon-JDRF Center for Beta cell replacement: clinical core.

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	basal and stimulated C-peptide levels		weekly within 1st month; monthly for 1 year	No
Secondary	glycated haemoglobin		monthly	No
Secondary	rapamycin and tacrolimus trough levels		every week for the first month, and monthly thereafter	Yes
Secondary	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	Yes