Pre Transplant Rapamycin Treatment in Islet Transplantation Alone (ITA-Rp)
Primary Purpose
Diabetes Mellitus, Type 1
Status
Completed
Phase
Phase 3
Locations
Italy
Study Type
Interventional
Intervention
rapamycin
Sponsored by
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring islet transplantation, insulin independence, C-peptide secretion
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
Sites / Locations
- Transplant Unit, IRCCS San Raffaele
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Rapamycin pre transplant
Arm 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).
Outcomes
Primary Outcome Measures
Evidence of insulin independence with adequate control of blood glucose (<140 mg/mL fasting; < 180 mg/mL post prandial, after the final infusion
Secondary Outcome Measures
basal and stimulated C-peptide levels
glycated haemoglobin
rapamycin and tacrolimus trough levels
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)
Full Information
NCT ID
NCT01060605
First Posted
February 1, 2010
Last Updated
February 1, 2010
Sponsor
IRCCS San Raffaele
Collaborators
Ministry of Education, Universities and Research, Italy, Juvenile Diabetes Research Foundation, Telethon-JDRF Center for Beta cell replacement: clinical core.
1. Study Identification
Unique Protocol Identification Number
NCT01060605
Brief Title
Pre Transplant Rapamycin Treatment in Islet Transplantation Alone
Acronym
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.
Study Type
Interventional
2. Study Status
Record Verification Date
January 2010
Overall Recruitment Status
Completed
Study Start Date
October 2001 (undefined)
Primary Completion Date
December 2005 (Actual)
Study Completion Date
September 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
IRCCS San Raffaele
Collaborators
Ministry of Education, Universities and Research, Italy, Juvenile Diabetes Research Foundation, Telethon-JDRF Center for Beta cell replacement: clinical core.
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes Mellitus, Type 1
Keywords
islet transplantation, insulin independence, C-peptide secretion
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Rapamycin pre transplant
Arm Type
Experimental
Arm 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).
Intervention Type
Drug
Intervention Name(s)
rapamycin
Other Intervention Name(s)
Rapamune
Intervention 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).
Primary Outcome Measure Information:
Title
Evidence of insulin independence with adequate control of blood glucose (<140 mg/mL fasting; < 180 mg/mL post prandial, after the final infusion
Time Frame
1 year
Secondary Outcome Measure Information:
Title
basal and stimulated C-peptide levels
Time Frame
weekly within 1st month; monthly for 1 year
Title
glycated haemoglobin
Time Frame
monthly
Title
rapamycin and tacrolimus trough levels
Time Frame
every week for the first month, and monthly thereafter
Title
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)
Time Frame
every week for the first month, and monthly thereafter
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Antonio Secchi, MD
Organizational Affiliation
Transplant Unit, IRCCS San Raffaele
Official's Role
Principal Investigator
Facility Information:
Facility Name
Transplant Unit, IRCCS San Raffaele
City
Milano
ZIP/Postal Code
20131
Country
Italy
12. IPD Sharing Statement
Citations:
PubMed Identifier
29654388
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.
Results Reference
derived
PubMed Identifier
21046356
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.
Results Reference
derived
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Pre Transplant Rapamycin Treatment in Islet Transplantation Alone
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