Effects of Pre-transplant Rapamycin Treatment and Tacrolimus Levels on the Outcome of Islet Transplantation Alone in Patients Receiving Edmonton Protocol.
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 11
- 试验地点
- 1
- 主要终点
- Evidence of insulin independence with adequate control of blood glucose (<140 mg/mL fasting; < 180 mg/mL post prandial, after the final infusion
研究概览
简要总结
Numerous changes to the original Edmonton protocol have been proposed in the attempt of improving the still unsatisfactory long-term function of ITA. Rapamycin may blunt the early inflammatory response to islet transplantation in the liver, thus favoring islet engraftment.
Aim of the investigators study was to evaluate the effect of a pre-transplant treatment with rapamycin in patients with type 1 diabetes receiving islet transplant alone and immunosuppression according to the Edmonton protocol.
详细描述
Pre-transplant rapamycin is administered for at least four weeks prior to the first islet infusion at the dose of 0.1 mg/kg (target trough levels: 8-10 ng/mL). During the pre-transplant rapamycin treatment rapamycin trough levels, renal and liver function, white blood cells count, total lymphocytes and lymphocytes subpopulations, hemoglobin, fibrinogen, cross-linked fibrin degradation products, C-reactive protein, exogenous insulin requirement every week for the first month, and monthly thereafter are measured. Induction and maintenance immunosuppressive regimen after each islet infusion is administered according to the Edmonton protocol (daclizumab, rapamycin, target trough levels: 12-15 ng/mL during the first 3 months and 10-12 ng/mL thereafter and tacrolimus 2 mg/day,target trough levels: 4-6 ng/mL). Islets are infused into the liver through the portal vein under local anesthesia Portography is performed before and after infusion. The islet function is evaluated measuring fasting C-pep, EIR, and HbA1c, immediately before the first islet infusion and subsequently every day for the first week, and then weekly for the first month ; every month after the last islet infusion for the first year and every 6 month thereafter.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 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
- •≥5 years of type 1 diabetes
- •hypoglycaemia unawareness
- •progression of chronic complications of diabetes despite intensive insulin regimen
排除标准
- •overt kidney disease
- •chronic liver disease
- •hepatic haemangioma
- •severe cardiomyopathy
- •untreated coronary artery disease
研究组 & 干预措施
Rapamycin pre transplant
Pre-transplant rapamycin is administered for at least four weeks prior to the first islet infusion at the dose of 0.1 mg/kg (target trough levels: 8-10 ng/mL).
干预措施: rapamycin (Drug)
结局指标
主要结局
Evidence of insulin independence with adequate control of blood glucose (<140 mg/mL fasting; < 180 mg/mL post prandial, after the final infusion
时间窗: 1 year
次要结局
- basal and stimulated C-peptide levels(weekly within 1st month; monthly for 1 year)
- glycated haemoglobin(monthly)
- rapamycin and tacrolimus trough levels(every week for the first month, and monthly thereafter)
- renal and liver function, white blood cells count, total lymphocytes and lymphocytes subpopulations (CD24, CD19), hemoglobin, fibrinogen (FG), cross-linked fibrin degradation products, C-reactive protein (CRP)(every week for the first month, and monthly thereafter)