Pre Transplant Rapamycin Treatment in Islet Transplantation Alone

NCT ID: NCT01060605

Last Updated: 2010-02-02

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 11 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2001-10-31
• Study Completion Date: 2009-09-30

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.

Conditions

Diabetes Mellitus, Type 1

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Rapamycin pre transplant

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).

Group Type: EXPERIMENTAL

rapamycin

Intervention Type: DRUG

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).

Interventions

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).

Intervention Type: DRUG

Other Intervention Names

Rapamune

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Ministry of Education, Universities and Research, Italy

OTHER

Sponsor Role: collaborator

Juvenile Diabetes Research Foundation

OTHER

Sponsor Role: collaborator

Telethon-JDRF Center for Beta cell replacement: clinical core.

UNKNOWN

Sponsor Role: collaborator

IRCCS San Raffaele

OTHER

Sponsor Role: lead

Responsible Party

IRCCS San Raffaele

Principal Investigators

Antonio Secchi, MD

Role: PRINCIPAL_INVESTIGATOR

Transplant Unit, IRCCS San Raffaele

Locations

Transplant Unit, IRCCS San Raffaele

Milan, , Italy

Countries

Italy

References

Benedini S, Ermetici F, Briganti S, Codella R, Terruzzi I, Maffi P, Caldara R, Secchi A, Nano R, Piemonti L, Alejandro R, Ricordi C, Luzi L. Insulin-mimetic effects of short-term rapamycin in type 1 diabetic patients prior to islet transplantation. Acta Diabetol. 2018 Jul;55(7):715-722. doi: 10.1007/s00592-018-1141-z. Epub 2018 Apr 13.

Reference Type: DERIVED

PMID: 29654388 (View on PubMed)

Piemonti L, Maffi P, Monti L, Lampasona V, Perseghin G, Magistretti P, Secchi A, Bonifacio E. Beta cell function during rapamycin monotherapy in long-term type 1 diabetes. Diabetologia. 2011 Feb;54(2):433-9. doi: 10.1007/s00125-010-1959-6. Epub 2010 Nov 3.

Reference Type: DERIVED

PMID: 21046356 (View on PubMed)

Other Identifiers

emendament 2001 to C99B901251

Identifier Type: -

Identifier Source: org_study_id