Islet Transplantation in Type 1 Diabetic Recipients of Renal Allografts, Using the Edmonton Protocol
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 8
- 主要终点
- independence from insulin injections with adequate control of blood glucose in subjects with Type 1 diabetes at one year post final transplant
研究概览
简要总结
Study hypothesis is that we can reproduce results of islet transplantation in type one diabetics in patients with a kidney transplant.
详细描述
This trial is designed to replicate the protocol currently being tested by the Immune Tolerance Network (ITN) in a population of patients that have been previously transplanted (recipients of functioning renal allografts) and are therefore immunosuppressed.
The data will be generated using substantially identical techniques for islet preparation, re transplantation with additional islets to meet the minimum islet cell mass, and an identical steroid-free post-transplant regimen utilizing sirolimus, low dose tacrolimus, and daclizumab.
3.1. Primary and secondary endpoints and additional measures
Study efficacy endpoints and additional measures are described in the following subsections. Measures relating to the islet preparation quality (Section 3.1.3) and other variables relating to key cellular and genetic markers (Section 3.1.4) followed during the study are not considered clinical outcome variables. Details describing requirements for efficacy testing are found in Section 6.1. Safety measures are described in Section 7.
3.1.1. Primary endpoint
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
- •Enrolling subjects must have Type 1 diabetes mellitus for more than 5 years, complicated by renal failure requiring a kidney transplant. The complicating situations are:
- •Reduced awareness of hypoglycemia,
- •Metabolic lability/instability,
- •Despite efforts at optimal glucose control, progressive secondary complications of diabetes as defined by:
- •i) Retinopathy- ii) Nephropathy- or
- •iii) Neuropathy-
排除标准
- •Severe co-existing cardiac disease, characterized by any one of these conditions:
- •recent myocardial infarction (within past 6 months), or
- •angiographic evidence of non-correctable coronary artery disease, or
- •evidence of ischemia on functional cardiac exam (•
- •Active alcohol or substance abuse-includes cigarette smoking (
- •Failure to fulfill major work, school, or home responsibilities;
- •Drinking in situations that are physically dangerous, such as while driving a car or operating machinery;
- •Recurring alcohol-related legal problems, such as being arrested for driving under the influence of alcohol or for physically hurting someone while drunk;
- •Continued drinking despite having ongoing relationship problems that are caused or worsened by the effects of alcohol.
- •Psychiatric disorder making the subject not a suitable candidate for transplantation,
- •History of non-adherence to prescribed regimens
- •Active infection including hepatitis C, hepatitis B, HIV, or TB (or under treatment for suspected TB)
- •Any history of malignancy except squamous or basal skin cancer
- •BMI > 26 kg/m2 or body weight > 70 kg for females and > 75kg for males at the screening visit. (An allowance for weight gain of up to +2 kg body weight is permitted between the screening visit and actual transplant. No transplant can be given to a female subject weighing > 72 kg or a male subject weighing > 77kg on the day of transplant. See Section 5.1 for minimum islet equivalent infusion requirements per recipient body weight.)
- •C-peptide response to arginine stimulation (5 gm I.V.) (any C-peptide ≥ 0.3 ng/mL at 2, 3, 4, 5, 7 and 10 min post infusion)
- •Inability to provide informed consent
- •Age less than 18 or greater than 65 years
- •Serum creatinine > 1.8 mg/dL, In addition, there must be no change in serum creatinine of > 0.4 mg/dl in the last 6 months.
- •Baseline Hb < 10.5 gm/dL in women, or < 13 gm/dL in men
- •Baseline LFT's outside of normal range with the exception of Gilberts Syndrome. n. Presence of gallstones (subjects may be eligible two weeks after a laparoscopic cholecystectomy ).
- •o. Hemangioma in liver on baseline ultrasound exam
- •p. Untreated proliferative retinopathy
- •q. Positive pregnancy test, intent for future pregnancy or male subjects' intent to procreate, failure to follow effective contraceptive measures, or presently breast feeding
- •r. Evidence of sensitization as determined by a general PRA with reactivity > 20%. t. Insulin requirement > 0.7 IU/kg/day
- •s. HbA1C > 12%
- •t. Inability to complete all scheduled visits during screening and post-transplant follow-up
- •u. Hyperlipidemia (fasting LDL cholesterol > 130 mg/dL, treated or untreated; and/or fasting triglycerides > 200 mg/dL).
- •v. Under treatment for a medical condition requiring chronic use of steroids at a dose > prednisone 5 mg/day w. Use of coumadin or other anticoagulant therapy (except aspirin) or subject with PT INR > 1.5 x. Addison's disease.y. EBV- negative subjects (use EBNA test for screening) to reduce potential risk of EBV infection for previously unexposed recipient.
研究组 & 干预措施
islet cell transplant
干预措施: Islet Infusion (Procedure)
结局指标
主要结局
independence from insulin injections with adequate control of blood glucose in subjects with Type 1 diabetes at one year post final transplant
时间窗: one year post final islet cell transplant
次要结局
未报告次要终点
研究者
Martha Pavlakis
Associate Professor of Medicine
Beth Israel Deaconess Medical Center