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It is a multicentre, sequential, phase II clinical trial, aiming at evaluating the allogeneic islet transplantation for the treatment of type 1 diabetes.
19 patients with type 1 diabetes will be included and ideally distributed evenly: patients with unstable diabetes without renal insufficiency (AI group for "islet alone" by the international customary determination) and patients with a functioning kidney transplant (IAK group for "islet after kidney"). The main endpoint will be defined by the restoration of normal glycemic control without insulin at 6 months after graft.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Allogeneic transplantation of intrahepatic islet | Experimental | Allogeneic transplantation of intrahepatic islet number required for insulin independence of obtaining, with a threshold dose of 9,000 IEQ/kg body weight of the recipient and a maximum sequence number of 3 infusions. The patient will receive after transplantation immunosuppressive therapy with Thymoglobulin for induction, Prograf and Cellcept, both of which are given throughout the duration of the study |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allogeneic transplantation of intrahepatic islet | Procedure |
|
| Measure | Description | Time Frame |
|---|---|---|
| restoration of normal glycemic control without insulin | the restoration of normal glycemic control without insulin therapy will be evaluated by measuring - A fasting glucose (> 8 hours) less than 1.25 g/L and a 2 hours glucose after oral intake of 75g of glucose, less than 2 g/L in a patient without insulin for at least 15 consecutive days during the the first 6 months from day 0. | 6 months after graft |
| Measure | Description | Time Frame |
|---|---|---|
| Restoration of normal glycemic control without insulin for a year | 1 year | |
| Obtaining an improvement in glycemic control | HbA1c <6.5%, with lower insulin doses by 30% | within 2 years after inclusion |
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Inclusion Criteria:
For patients in group IA
Glomerular filtration rate estimated by the MDRD> 50 ml/min/1.73m2
No perception of hypoglycaemia (less than 0.54 mg/dl glucose) at least one value documented in the two years preceding and/or
Occurrence of at least one severe hypoglycemic episode (with a third required) and unexplained in the two years before and/or at least two episodes of ketoacidosis per year
Average HbA1c> 8.5% over two years, despite intensified treatment (basal pattern, bolus)
• For patients in the IAK
functional renal graft for at least 1 year
glomerular filtration rate> 50 ml/min/1.73 m2
proteinuria <0.5 g/day
Absence of acute rejection in renal previous 6 months
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Pierre CATTAN, MD PhD | Contact | 33 1 42494786 | pierre.cattan@sls.aphp.fr |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Saint Louis hospital | Recruiting | Paris | Île-de-France Region | 75010 | France |
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| ID | Term |
|---|---|
| D003920 | Diabetes Mellitus |
| ID | Term |
|---|---|
| D044882 | Glucose Metabolism Disorders |
| D008659 | Metabolic Diseases |
| D009750 | Nutritional and Metabolic Diseases |
| D004700 | Endocrine System Diseases |
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| Obtaining a remission of diabetes | The remission of diabetes is defined by the normality of blood glucose or insulin without lHbA1c. The normality of blood glucose is defined below 1.20 g/L and postprandial fasting glycemia less than 1.60 g/L in the book self-monitoring (including 6/7 blood glucoses during the previous 3 days evaluation visit). Normal HbA1c is defined as less than 6.5%. | within 2 years after inclusion |
| Improved metabolic profile determined by the OGTT and hyperglycemic clamp | within 2 years after inclusion |
| Decreased glycemic variability | defined on blood glucose and / or glucose holter | within 2 years after inclusion |
| Reduction of oxidative stress assessed by the urinary excretion of 24 hours of 8-iso-PGF2 rates. | within 2 years after inclusion |
| Decrease in the frequency, severity or poor perception of hypoglycaemia defined Hypo score | within the 2 years after inclusion |
| quality of life | defined by questionnaires DQOL and SF-36 | within 2 years after inclusion |
| term graft survival | defined by the rate of C-peptide | within 2 years of inclusion |
| beta-cell function | based on beta-score | 2 years |
| potential of each infusion of islets | number of IEQ/kg of recipient required to reduce the daily insulin dose of 1 unit | within 2 years after inclusion |
| degenerative complications of diabetes | 2 years |