Islet After Kidney Transplantation (IAK) in Patients With Type 1 Diabetes Using a Sirolimus/Tacrolimus/MMF-Based Immunosuppressive Regimen
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 发起方
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- Percent of subjects who have achieved insulin sufficiency post transplant.
研究概览
简要总结
The purpose of this study is to determine the safety of islet transplantation in patients with type 1 diabetes who have had a successful kidney transplant and have been maintained for at least three months on anti-rejection medications consisting of any combination of sirolimus, tacrolimus, MMF or prednisone (5 mg/day or less). Another purpose is to determine the effectiveness of an islet transplant in inducing insulin independence and whether or not an islet transplant improves quality of life for kidney transplants patients with type 1 diabetes.
详细描述
Insulin is a hormone that helps the body use sugar and keeps blood sugar levels normal. Special cells in the human body, called beta cells, make insulin. Beta cells are found inside small groups of cells called "islets." Islets are found scattered in the pancreas gland. Type 1 diabetes is caused by damage to these insulin-making cells. Type 1 diabetic patients need insulin shots because their body does not make enough insulin. Even with insulin shots, many diabetic patients develop damage to the heart, blood vessels, nerves, eyes and kidneys. Research studies suggest that these problems are caused by blood sugar levels being too high.
Another way to treat diabetes is by giving the patient a pancreas transplant. The pancreas transplant gives the patient new insulin-making cells. If the pancreas transplant works, the patient does not need insulin shots. Pancreas transplantation is considered major surgery, and things can go wrong after surgery. Transplantation of just the islets, and not the rest of the pancreas, can be done without a major surgery. Research doctors have been studying islet transplantation to determine whether subjects who undergo the procedure can get off insulin shots, without the dangers of a major surgery.
In 2000, a group of research doctors in Edmonton, Canada reported that 3 out of 4 research subjects given islet transplants from brain-dead donors did not need insulin shots for approximately 2 years after transplantation. The research doctors from Edmonton have also reported that most islet transplant recipients in their study start to need insulin shots again with longer follow-up. So far, only about 1 out of 10 of the research subjects in the original Edmonton trial remain off of insulin 5 years after their transplant. The reasons that islet transplants stop working well enough and the recipients need to start insulin again are not known at this time. As with any type of transplant, all of the research subjects receiving islets from donors needed medicine to stop their bodies from rejecting the transplants. This study uses a few additional medications/vitamins that were not included in the Edmonton study that may improve the long-term outcome of islet transplantation. Some research studies suggest that for subjects with type 1 diabetes, an islet transplant may also help the kidney transplant work better and last longer.
This study is being performed to confirm that islet after kidney transplantation (IAK) is a safe and effective procedure for kidney transplant patients with type 1 diabetes who are on any combination of sirolimus, tacrolimus, MMF or prednisone (5 mg per day or less) anti-rejection medications for the care of their kidney transplant. Subjects will be followed closely for two years after islet transplant to monitor blood sugar control, the health of the kidney transplant, and changes in quality of life.
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. Documentation of negative basal and stimulated C-peptide (a basal level of \/=60 ml/min and albumin excretion \3 months.
- •* Stable immunosuppression consisting of any combination of sirolimus, tacrolimus, MMF or \ 3.5 g/dl, and PT and PTT \
排除标准
- •Poor renal allograft function (serum creatinine > 1.6 mg/dl, creatinine clearance < 60ml/min, albumin excretion >300 mg/24hr)
- •History of acute rejection related to renal graft in last 12 months or "high risk" for acute rejection (more than one previous renal transplant, PRA >25%, positive kidney crossmatch by B, T, flow cytometry)
- •Current immunosuppression therapy with corticosteroids >5mg/day.
- •Significant liver disease (including elevation of liver enzymes > twice the upper limit of normal for each of ALT and AST, bilirubin > 2 mg/dl, albumin < 3.5 g/dl, liver masses including portal vein thrombosis, evidence of portal hypertension, or significant, untreated gallbladder disease (i.e., gallstones).
- •Significant cardiovascular disease, including non-correctable coronary artery disease with ejection fraction < 50% and/or recent myocardial infarction (within last 12 months); extensive peripheral vascular disease not correctable by surgery or untreated proliferative retinopathy.
- •Recent unresolved acute infection, or chronic infection, including tuberculosis, HIV, HBV, HCV, CMV or positive skin test for TB.
- •Any history of malignancy, except squamous or basal skin cancer or in situ cancer of the cervix.
- •Recent history of non-compliance, or inability to demonstrate capacity to comply with strict blood glycemic control and insulin pump therapy.
- •Psychiatric illness that is untreated, or likely to interfere significantly with transplantation despite treatment.
- •Presence of preformed antibodies on panel reactive antibody screening > 25%.
- •Body mass index (BMI) greater than
- •Age less than 18 years or greater than 65 years.
- •Presence of a chronic disease that must be chronically treated with one or more of the following medications: glucocorticoids, diazoxide, bumetanide, haloperidol, chlorpromazine, desipramine, doxepin, imipramine, levodopa, morphine, L-asparaginase, cyclophosphamide, isoniazid, heparin, nalidixic acid, or any other agents that may adversely influence glycemic control and which may confound the interpretation of Graft Success post-transplant.
- •Pregnant women, women intending future pregnancy, women of reproductive potential who are unable or unwilling to follow effective contraceptive measures for the duration of immunosuppressive therapy, and women presently breast feeding are ineligible due to the unknown effects of these drugs on the fetus and nursing infant.
- •Active alcohol or substance abuse, including cigarette smoking (must be abstinent for > 3 months).
- •Hyperlipidemia (total cholesterol > 260 mg/dl, LDL > 130 mg/dl, and/or triglycerides > 300 mg/dl) despite appropriate treatment.
- •Anemia (Hgb < 12 g/dl) or other hematologic disorders that require medical attention.
- •Increased risk of bleeding (platelet count < 80,000; INR > 1.5), other chronic hemostasis disorders, or treatment with chronic anticoagulant therapy (i.e., heparin or warfarin).
研究组 & 干预措施
1
Islet transplantation
干预措施: Islet Transplantation (Procedure)
1
Islet transplantation
干预措施: Islet cell transplantation (Biological)
结局指标
主要结局
Percent of subjects who have achieved insulin sufficiency post transplant.
时间窗: 3, 6, 12, and 24 months
次要结局
- Insulin use </= 0.2 units/kg/day(3, 6, 12, and 24 months)
- Reduction/elimination of hypoglycemic episodes(3, 6, 12, and 24 months)
- Stimulated C-peptide response >0.6 ng/ml(3, 6, 12, and 24 months)
- HgAlc</= 6.5%(3, 6, 12, and 24 months)