Trial Comparing Metabolic Efficiency of Islet Graft to Intensive Insulin Therapy for Type 1 Diabetes's Treatment (TRIMECO)
Diabetes Mellitus, Type 1
About this trial
This is an interventional treatment trial for Diabetes Mellitus, Type 1 focused on measuring Islet Cell Transplantation, Metabolic Diseases, Endocrine System Diseases
Eligibility Criteria
Inclusion Criteria:
- Patient with type 1 diabetes or C-peptide negative diabetes Diabetes duration > 5 years
- No residual insulin secretion (plasmatic basal and stimulated C-peptide < 0.3 ng/ml)
- HbA1c considered acceptable by the selection committee
- Insulin needs < 0.85 IU/kg/day
Islet cell infusion after kidney graft
- Patient with terminal renal failure and functional kidney graft for at least 6 months (creatinine clearance greater than or equal to 35 ml/min)
- Patient whose glycaemic control obtained with insulin therapy could threaten kidney graft survival and/or significantly alter quality of life. This situation is assessed by a diabetologist
Islet cell infusion only: patient with major glycaemic variability despite proper intensive insulin therapy, closely monitored by a diabetologist. Poor glucose control, assessed by a diabetologist, endangers the patient's life and/or significantly alters personal, social, professional and family quality of life. At least one of these criteria must be fulfilled :
- Hypoglycaemia unawareness, blood glucose level < 3mmol/L or 0.54 mg/L
- At least 2 severe hypoglycaemia events (defined by the necessity of a third party's assistance) per year or a ketoacidosis requiring patient's hospitalization during the last year.
- Impairment of quality of life or life-threat for patient or other persons, or progressive complications despite optimal insulin therapy
- Social Security membership or benefit from Social Welfare
Exclusion Criteria:
- Age< 18 and > 65
- Diabetes duration < 5 years
- Criteria specifically related to the islet intraportal injection procedure: hemostasis problem, haemoglobin level < 11g/dL for women and <12g/dL for men, abnormalities of complete blood count, documented liver pathology (alkaline phosphatases, gamma GT, transaminases levels over twice normal values) ; pancreatitis history, gallbladder stones that could potentially migrate; HLA hyperimmunisation (PRA >20%).
Criteria related to diabetes complications :
- Non-stabilized proliferating diabetic retinopathy
- Creatininaemia > 16 mg/dL
- Exclusion criteria non-specifically related to islet infusion: evolutive vascular disease, evolutive cardiopathy (especially myocardial infarction less than 6 months ago, cerebrovascular stroke less than 6 months ago, evolutive arteritis with trophic disorders) ; systemic infection including hepatitis C and HIV ; leuconeutropenia ; thrombocytopenia, non-stabilized neoplastic pathology ; pregnancy or project of pregnancy within the next 24 months ; poor therapeutic compliance
- Criteria related to immunosuppressive protocol : renal failure (glomerular filtration < 35 ml/min/1.73 m²) and/or proteinuria > 0.5 g/24h ; non-treated hyperlipidemia (LDL-C > 130 mg/dL) ; blood pressure > 160/100 mmHg
- Clinical insulin resistance : assessed by patient's weight, BMI and exogenous insulin requirements (BMI > 30 kg/m² or insulin dose > 0.85 UI/kg/day)
Sites / Locations
- University Hospital, Department of Endocrinology
- University Hospital Gabriel Montpied, Department of Endocrinology
- University Hospital Besançon, Department of Endocrinology
- University Hospital, Department of Endocrinology
- University Hospital, Department of Endocrinology
- University Hospital, Department of General Surgery and Endocrinology
- University Hospital, Department of Endocrinology
- HCL Sud, Department of Endocrinology
- Hopitaux Universitaires de Genève, Department of Visceral Surgery and Transplant
Arms of the Study
Arm 1
Arm 2
Experimental
Active Comparator
immediate registration on islet graft list
delayed registration on islet graft list
group 1 'immediate registration on infusion waiting list' : patients who will be immediately registrated on islet cell infusion waiting list after randomization. Intervention : Procedure/surgery (islet graft)
group 2 'delayed registration on infusion waiting list' : patients who will be registrated 6 months later on islet cell infusion waiting list after randomization. Intervention : Procedure/surgery (islet graft)