Randomized Controlled Trial Comparing the Metabolic Efficiency of Allogeneic Pancreatic Islet Transplantation to Intensive Insulin Therapy for the Treatment of Type 1 Diabetes
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 50
- 试验地点
- 9
- 主要终点
- ß score evaluation 6 months after first infusion (group 1 'immediate registration on infusion waiting list') or 6 months after inclusion (group 2: 'delayed registration on infusion waiting list')
研究概览
简要总结
Efficacy of pancreatic islet transplantation at 6 months compared to an intensive insulin therapy for 2 categories of patients: patients with unstable diabetes and patients who underwent kidney transplantation.
详细描述
Efficacy of pancreatic islet transplantation at 6 months compared to an intensive insulin therapy for 2 categories of patients: patients with unstable type 1 diabetes versus patients with unstable type 1 diabetes and who underwent kidney transplantation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 64 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
immediate 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)
干预措施: Islet Graft (Biological)
delayed registration on islet graft list
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)
干预措施: Islet Graft (Biological)
结局指标
主要结局
ß score evaluation 6 months after first infusion (group 1 'immediate registration on infusion waiting list') or 6 months after inclusion (group 2: 'delayed registration on infusion waiting list')
时间窗: 6 months after first infusion (group 1) or 6 months after inclusion (group 2)
Metabolism evaluated by ß score. This score uses 4 intermediate scores ranging from 0 to 2 associated with the following 4 indicators: HbA1c, basal C peptide (or stimulated C-peptide), daily insulin dose (U/kg) or intake of oral antidiabetic drugs and fasting glycaemia. The total of the intermediate scores ranges from 0 to 8. Islet graft will be considered as successful if the ß score is equal to or greater than 6
次要结局
- Evaluation of metabolism indicators : ß-score and individual analysis of the 4 components of the ß-score(6 and 12 months)
- Measure of quality of life (SF36, DQOL, DHP)(at inclusion time, at 6 months and at 12 months after first infusion (group 1) or after inclusion (group 2))
- Cost evaluation of islet cell infusion(6 months)
- Evaluation of side effects and iatrogenic effects(at 6 months and 12 months after infusion)