Sequential Islet Transplantation With Steroid Free Immunosuppression for Type 1 Diabetes
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 14
- 试验地点
- 1
- 主要终点
- Composite Criteria: Insulin Independence and Glycosylated Hemoglobin (HbA1c) Under 6.5% at One Year
研究概览
简要总结
The restoration of endogenous insulin secretion carries significant hopes for shifting the paradigm of life long exogenous insulin therapy in selected groups of patients with type 1 diabetes(T1D). After decades of frustrating clinical attempts, the Edmonton group set up in 2000 new standards for islet transplantation in patients with brittle T1D by achieving insulin independence in 80 percent of patients. These seminal results have however proved much more difficult to duplicate than initially expected.
This single center phase 2 clinical trial, duplicating the Edmonton protocol, is designed for confirming the consistent short term efficacy and safety of sequential islet allotransplantation with steroid free immunosuppression in patients with severe T1D.
详细描述
The short term effectiveness of islet transplantation for alleviating hypoglycemia and controlling glucose homeostasis while limiting or even avoiding the nedd for exogenous insulin has been established despite protocol modifications in donor selection, islet preparation or recipient treatment, insulin independence with adequate metabolic control was however rarely prolonged beyond two years. The most frequently proposed explanations include chronic allogenic rejection, recurrence of autoimmunity and beta cell toxicity from administered immunosuppressive drugs.
Fourteen patients were enrolled in this single center phase 2 trial initiated in 2003. Eligible patients were males or females between 18 and 65 years of age, with type 1 diabeted documented for more than 5 years, arginine stimulated C-peptide lower than 0.2ng/ml, and hypoglycemia awareness or documented metabolic lability. Exclusion criteria included body mass index greater than 28Kg/m2, unstable arteriopathy or heart disease, active infection, previous transplantation, insulin daily requirements above 1.2 UI/kg, creatinin clearance below 60 ml/mn/m2 or urinary albumin excretion above 300 mg/day, malignancy, smoking, desire for pregnancy, psychiatric disorders and lack of compliance. The study primary efficacy endpoint was graft survival defined as insulin independence and HbA1c<6.5%. Secondary outcomes were graft function and metabolic control.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •type 1 diabetes documented for more than 5 years
- •arginine stimulated C-peptide lower than 0.2 ng/mL
- •one of the following:hypoglycemia unawareness OR metabolic lability documented by one or more severe hypoglycemias or two or more hospital admissions for ketoacidosis within the previous year.
排除标准
- •body mass index greater than 28 kg/m2
- •non stable arteriopathy or heart disease
- •active infection
- •previous transplantation
- •hyperimmunization
- •insulin daily needs above 1.2 U/Kg
- •creatinine clearance below 60 ml/mn or urinary albumin excretion above 300 mg/d
- •malignancy
- •desire for pregnancy
- •psychiatric disorders
- •lack of compliance
研究组 & 干预措施
islet transplantation
Each participant received up to three sequential fresh islet infusions within three months.
干预措施: islet transplantation (Procedure)
islet transplantation
Each participant received up to three sequential fresh islet infusions within three months.
干预措施: daclizumab - sirolimus - tacrolimus (Drug)
结局指标
主要结局
Composite Criteria: Insulin Independence and Glycosylated Hemoglobin (HbA1c) Under 6.5% at One Year
时间窗: 1 year
The percentage of insulin independents subjects with an HbA1c less than 6.5% at one year after last transplant
次要结局
- Hypoglycemic Events(day 0 to day 365)
- Plasma C-peptide(1 year)
- HbA1c < 6.5%(1 year)
- Percentage of Time Spent in Hypoglycemia (<0.70 mg/L)(1 year)
- Number of Adverse Events(1 year)