Transplantation d'Ilots Pancreatiques Allogeniques Adultes Pour le Traitement du Diabete Insulino-dependant: Etude GRAGIL 2.
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 22
- 试验地点
- 8
- 主要终点
- The rate of insulin-independence, judged upon the following criteria : HbA1c < 6.1%,
研究概览
简要总结
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 brittle type 1, insulin-dependent diabetes mellitus and to improve their metabolic control.
详细描述
The general objective is to demonstrate the beneficial effect of islet allotransplantation in patients with brittle type 1 diabetes with no endogenous insulin secretion, for whom the risk of the spontaneous course of the disease is judged to be worse than the transplantation-related risk. The specific objective is to establish reference data for islet transplantation in non-uremic patients with brittle diabetes, in a multicentric network setting, using the Edmonton protocol.
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 mellitus
- •Disease duration > 5 years
- •Despite intensive insulin therapy with tight endocrinologist supervision, persistence of the following conditions : hypoglycemia unawareness (< 54 mg/dl) ; brittleness with at least two episodes of severe hypoglycemia ((defined by the need for assistance to correct the blood glucose level) or ketoacidosis per year , or often enough that the diabetologist judges the frequency to be life-threatening, the risk of transplantation and immunosuppression being judged to be less than the risk of the spontaneous course of uncontrolled diabetes
- •Basal and stimulated plasma C-peptide < 0.2 ng/ml
- •Creatinine clearance ≥ 50 ml/min/1.73 m2 and proteinuria < 0.5 g/24h
排除标准
- •Severe cardiovascular disease (recent myocardial infarction, unstable coronaropathy…)
- •Severe systemic infection, including hepatitis C or B viral infection, HIV infection or tuberculosis
- •Past or present neoplasia (with the exception of non melanoma skin cancers)
- •Body weight > 70 kg in women and BW > 75 kg in men or BMI > 26
- •Stimulated C-peptide ≥ 0.3 ng/ml upon Glucagon or Arginine stimulation
- •Age < 18 years or > 65 years
- •Creatinine clearance < 50 ml/min/1.73 m2
- •Albuminuria > 300 mg /24h or proteinuria > 0.5 g/24h
- •Hemoglobinemia < 120 g/l in women or < 130 g/l in men
- •Liver disease (enzymes > 1.5 N) such as cirrhosis or hepatitis
- •Liver hemangioma
- •Untreated proliferating diabetic retinopathy
- •Pregnancy, lactation, pregnancy project or absence of efficient contraception
- •Previous transplantation or immunization as judged by anti-HLA antibodies (> 20%)
- •Insulin needs > 0.7 IU/kg/d or > 50 IU
- •HbA1c > 12 %
- •Any medical condition needing the chronic use of steroids
- •Addison disease
- •Any hemostasis disorder needing a prolonged treatment with anticoagulation drugs. Low-dose aspirin is permitted. coagulation disorders contraindicating the procedure, such as platelet count < 100000/mm
- •Serious life-threatening disease
- •Medical or surgical history potentially influencing the absorption, distribution, metabolism and clearance of drugs
- •Uncontrolled hypercholesterolemia (> 350 mg/dl, 9.1 mmol/l) or hypertriglyceridemia (> 500 mg/dl, 5.6 mmol/l)
- •Leukocytes < 4500/mm3, neutrophils < 2000/mm3, platelets < 100000/mm3
- •Any medical or psychosocial condition susceptible to interfere with the study, such as drug abuse or recent alcohol abuse
- •Poor therapeutic observance
- •Failure to communicate or cooperate with the investigator
结局指标
主要结局
The rate of insulin-independence, judged upon the following criteria : HbA1c < 6.1%,
post-prandial blood glucose < 180 mg/dl, mean amplitude of glycemic excursion (MAGE index)
< 60 mg/dl, basal C-peptide > 0.5 ng/ml. This insulin independent rate will be assessed 6 months
and 12 months following transplantation.
次要结局
- The rate of success according to the DiaCell composite score defined by the following 4 items : functional islet graft, defined by a basal C-peptide > 0.5 ng/ml;
- good metabolic control, defined by HbA1c ≤ 6.5%; disappearance of hypoglycemic events; reduction in exogenous insulin needs ≥ 30%.
- Morbidity and quality of life will also be assessed.