Clinical trial NCT01060605: Pre Transplant Rapamycin Treatment in Islet Transplantation Alone
Official title: Effects of Pre-transplant Rapamycin Treatment and Tacrolimus Levels on the Outcome of Islet Transplantation Alone in Patients Receiving Edmonton Protocol.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes Mellitus, Type 1
Keywords: islet transplantation
insulin independence
C-peptide secretion
Lead sponsor: IRCCS San Raffaele
Sponsor class: OTHER
Collaborators: name: Ministry of Education, Universities and Research, Italy
name: Juvenile Diabetes Research Foundation
name: Telethon-JDRF Center for Beta cell replacement: clinical core.
First posted: 2010-02-02
Enrollment: 11
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Evidence of insulin independence with adequate control of blood glucose (<140 mg/mL fasting; < 180 mg/mL post prandial, after the final infusion
timeFrame: 1 year
Secondary outcomes:
measure: basal and stimulated C-peptide levels
timeFrame: weekly within 1st month; monthly for 1 year
measure: glycated haemoglobin
timeFrame: monthly
measure: rapamycin and tacrolimus trough levels
timeFrame: every week for the first month, and monthly thereafter
measure: 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)
timeFrame: every week for the first month, and monthly thereafter
Other outcomes:
Locations:
city: Milano
country: Italy
facility: Transplant Unit, IRCCS San Raffaele
Study officials:
affiliation: Transplant Unit, IRCCS San Raffaele
name: Antonio Secchi, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.