Transplantation of Pancreatic Islets in Patients With Type 1 Diabetes Mellitus and Functional Kidney Graft

Study Overview
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Brief Summary
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This research project is supported by a multicentric network of collaborators whose goal is to assess the efficacy of transplanting allogenic pancreas islets to restore insulin secretion in patients with type 1, insulin-dependent diabetes mellitus with kidney transplantation and to improve their metabolic control.

Detailed Description
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The main objective is to demonstrate the beneficial effect of islet allotransplantation in patients with type 1 diabetes with no endogenous insulin secretion, and with a functional kidney graft. The other objectives are to evaluate the conditions for the efficacy of islet cell transplantation, to assess the improvement in quality of life and the cost of the islet cell transplantation.

Official Title
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Transplantation d'îlots pancréatiques allogéniques Adultes Pour le Traitement du diabète insulinodépendant. Etude GRAGIL 1

Conditions
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Type 1 Diabetes Mellitus

Intervention / Treatment
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* Procedure: human pancreatic islet transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 1 diabetes mellitus Disease duration > 5 years ketose antecedents Basal and stimulated plasma C-< 0.2 ng/ml,<0.06 nmol/l (glycemia must be measured simultaneously_ 1.20 g/l or 6.6 mM, stimulation with glucagon IV 1 mg -Measured at à T0 and T 6 min) Established kidney graft ≥ 6 months Current creatinine clearance: ≥ 50 ml/min/1.73 m² and Proteinuria < 0.5 g/24h HbA1C< 12% Exclusion Criteria: Hemostasis problems Documented hepatic pathology Patient under 18 or over 65 year-old Women with body weight over 70 kg (tolerance of 2 kg between inclusion day and transplantation day) or BMI > 26 Men with body weight > 75 kg (tolerance of 3 kg between inclusion day and transplantation day) or BMI > 26 insuline needs > 0.7 U/kg/j or 50 U/j Serious life-threatening pathology untreated hyperlipidemia Hypersensitivity to drugs rapamycine-alike Liver disease (transaminases or total bilirubin ≥ 3N) Failure to communicate or cooperate with the investigator Exclusion criteria that are specific to the use of Rapamycine Hypercholesterolemia (> 350mg/dl, 9,1 mmol/l) not controlled Hypertriglyceridemia (> 500 mg/dl, 5,6 mmol/l) not controlled Leukocytes > 4500 /mm3 , neutrophils > 2000/ mm3, platelets > 100000/ mm3 Any clinical or biological pathology that could interfere with the study Past or present neoplasia (with the exception of non melanoma skin cancers) Any hemostasis disorder needing a prolonged treatment with anticoagulation drugs. Low-dose aspirin is permitted. Pregnancy, lactation, pregnancy project or absence of efficient contraception Any medical or psychosocial condition susceptible to interfere with the study, such as drug abuse or recent alcohol abuse

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Procedure: human pancreatic islet transplantation|human pancreatic islet transplantation|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of insulin-independence at 6 and 12 months after transplantation, duration of insulin-independence, survival curves |  | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance (Measurement of portal pressure during islet injection) Quality of life (Questionnaires SF-36 and DQOL at inclusion time, then every 6 months during their waiting period and then 6 months and 12 months after transplantation) Costs |  | 12 months |