Pre Transplant Rapamycin Treatment in Islet Transplantation Alone (ITA-Rp)

This study has been completed.
Sponsor:
Collaborators:
Ministry of Education, Universities and Research, Italy
Juvenile Diabetes Research Foundation
Telethon-JDRF Center for Beta cell replacement: clinical core.
Information provided by:
IRCCS San Raffaele
ClinicalTrials.gov Identifier:
NCT01060605
First received: February 1, 2010
Last updated: NA
Last verified: January 2010
History: No changes posted
  Purpose

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.


Condition Intervention Phase
Diabetes Mellitus, Type 1
Drug: rapamycin
Phase 3

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Effects of Pre-transplant Rapamycin Treatment and Tacrolimus Levels on the Outcome of Islet Transplantation Alone in Patients Receiving Edmonton Protocol.

Resource links provided by NLM:


Further study details as provided by IRCCS San Raffaele:

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 [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • basal and stimulated C-peptide levels [ Time Frame: weekly within 1st month; monthly for 1 year ] [ Designated as safety issue: No ]
  • glycated haemoglobin [ Time Frame: monthly ] [ Designated as safety issue: No ]
  • rapamycin and tacrolimus trough levels [ Time Frame: every week for the first month, and monthly thereafter ] [ Designated as safety issue: Yes ]
  • 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 ] [ Designated as safety issue: Yes ]

Enrollment: 11
Study Start Date: October 2001
Study Completion Date: September 2009
Primary Completion Date: December 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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).
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).
Other Name: Rapamune

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

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01060605

Locations
Italy
Transplant Unit, IRCCS San Raffaele
Milano, Italy, 20131
Sponsors and Collaborators
IRCCS San Raffaele
Ministry of Education, Universities and Research, Italy
Juvenile Diabetes Research Foundation
Telethon-JDRF Center for Beta cell replacement: clinical core.
Investigators
Principal Investigator: Antonio Secchi, MD Transplant Unit, IRCCS San Raffaele
  More Information

No publications provided by IRCCS San Raffaele

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Antonio Secchi, IRCCS San Raffaele
ClinicalTrials.gov Identifier: NCT01060605     History of Changes
Other Study ID Numbers: emendament 2001 to C99B901251
Study First Received: February 1, 2010
Last Updated: February 1, 2010
Health Authority: Italy: Ethics Committee

Keywords provided by IRCCS San Raffaele:
islet transplantation
insulin independence
C-peptide secretion

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 1
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Autoimmune Diseases
Immune System Diseases
Sirolimus
Everolimus
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 28, 2014