Calcineurin Inhibitor (CNI)-Free Immunosuppressive Regimen in T1D Patients Receiving Islet Transplantation (ECIT-1)
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Multi-step Trial Towards Single Donor Islet Transplantation in Type 1 Diabetic Patients, Using Calcineurin Inhibitor-free Immunosuppression|
- The Proportion of Insulin Free Patients 3 Years After the Last Islet Infusion [ Time Frame: 3 year ] [ Designated as safety issue: No ]Insulin independence is defined as no need for exogenous insulin, with adequate glycemic control [i.e., glycated hemoglobin <7% (normal range 3.5 - 6.0%), fasting glucose levels not exceeding 140 mg/dL (7.8 mmol/L) more than three times per week and 2-hour postprandial levels not exceeding 180 mg/dL (10 mmol/L) more than four times per week].
- Insulin Independence With Adequate Glycemic Control Throughout Follow-up [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
- Glycated Hemoglobin Levels Throughout Follow-up [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
- Basal and Stimulated Blood C-peptide Levels in Response to Arginine Challenge Throughout Follow-up [ Time Frame: up to 3 year ] [ Designated as safety issue: No ]
- the Reduction in Insulin Requirement Compared to Baseline [ Time Frame: up to 3 years ] [ Designated as safety issue: No ]
- Severe Hypoglycemic Events Since Completion of Transplant [ Time Frame: up to 3 years ] [ Designated as safety issue: Yes ]
- Any Adverse Event Throughout Follow-up [ Time Frame: up to 3 years ] [ Designated as safety issue: Yes ]Among study participants there were no reports of death, post-transplantation lymphoproliferative disease, cancer, or opportunistic infections. There was no evidence of cytomegalovirus disease, infection or serological activation (CMV early antigens negative during the whole follow-up), nor of Epstein-Barr clinical and serological reactivation (all patients were antibodies anti EBV positive before transplant, as per the inclusion criteria).
|Study Start Date:||October 2006|
|Study Completion Date:||June 2012|
|Primary Completion Date:||June 2009 (Final data collection date for primary outcome measure)|
|Experimental: CNI-free single-group||
Drug: CNI free immunosuppression
Immunosuppression consisted of: (i) pre-Tx rapamycin treatment (0.1 mg/kg/day) for at least 30 days; (ii) induction therapy with ATG (1.5 mg/kg/day for 4 days starting at day -1) and a steroid bolus (methyl-prednisolone 500 mg, day -1) plus low dose steroids (prednisone, 10 mg/day) and interleukin-1 (IL-1) receptor antagonist (100 mg/day) for 2 weeks (with ATG and steroid bolus administered only prior to the 1st islet infusion; (iii) maintenance with rapamycin (0.1 mg/kg/day) plus mycophenolate mofetil (2 g/day).
Other Name: Kineret, Rapamune, Thymoglobulin, Myfortic
We designed the clinical trial as a single-arm, phase 1-2 trial conducted in two transplant centers (San Raffaele Scientific Institute, Milan, Italy; Cell Isolation and Transplantation Center, University of Geneva, Geneva, Switzerland) which used a common protocol for islet preparation, post-transplantation patient management and data collection. The trial is exploratory in nature and the target enrollment is 10 patients. The recruitment is competitive between the two centers and each patient is to receive at least 10,000 IE/kg. Up to three islet infusions are allowed per patients until insulin independence is reached, provided that partial islet function (i.e., fasting C-peptide ≥0.3 ng/mL) is maintained between infusions. We planned an individual follow-up of 3 years after the last islet infusion.
Patients with type 1 diabetes are eligible for this study. Major criteria for inclusion are: age 18-65 years; type 1 diabetes with onset <40 years of age; insulin treatment of at least 5 years at the time of enrollment; stimulated C-peptide in response to arginine <0.5 ng/ml; multiple (three or more) daily insulin injections or Continuous Subcutaneous Insulin Infusion; self-blood glucose monitoring ≥3 times/day; high glycemic instability and/or hypoglycemia unawareness; inability to consistently attain a glycated hemoglobin target of <7.5 % without severe hypoglycemia (defined as an hypoglycemic episode requiring the assistance by another person for its resolution) in the past 36 months despite medical management by a diabetes specialist. Major criteria for exclusion are: HbA1c >12%; BMI >30 kg/m2, or insulin requirement > 0.8 IU/kg/day; poorly controlled hypertension; untreated proliferative diabetic retinopathy; presence or history of macroalbuminuria (>300mg/g day) or estimated glomerular filtration rate <60 ml/min/1.73 m2 for females or <70 ml/min/1.73 m2 for males.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01346085
|IRCCS San Raffaele Scientific Institute|
|Milan, Italy, 20132|
|Universitè de Geneve|
|Geneve, Switzerland, 1211|
|Principal Investigator:||Lorenzo Piemonti, MD||Fondazione Centro San Raffaele del Monte Tabor|
|Principal Investigator:||Thierry Berney, MD||Universitè de Geneve|
|Study Chair:||Antonio Secchi, MD||Fondazione Centro San Raffaele del Monte Tabor|
|Study Director:||Paola Maffi, MD||Cantro San Raffaele del Monte Tabor|