Islet Cell Transplantation Alone and CD34+ Enriched Donor Bone Marrow Cell Infusion in Patients With Type 1 Diabetes Mellitus; Steroid Free Regimen
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 3
- 试验地点
- 2
- 主要终点
- The Achievement of Persistent Islet Function Following Cessation of Immunosuppression.
研究概览
简要总结
SPECIFIC AIMS:
- To reverse hyperglycemia and insulin dependency in patients with Type 1 diabetes mellitus by islet cell transplantation.
- To induce a state of donor specific tolerance and eliminate the need for continuous immunosuppressive therapy by simultaneous transplantation of donor bone marrow cells with islets and utilization of the monoclonal antibody Campath-1H for induction of Immunosuppression.
- To assess long-term function of successful islet cell transplants in patients with Type 1 diabetes mellitus.
- To determine whether the natural history of the microvascular, macrovascular and neuropathic complications are altered following successful transplantation of islet
详细描述
In our current protocol (IRB #2000/0024) the immunosuppressive regimen, comprised of induction with daclizumab and maintenance therapy with sirolimus and tacrolimus, has been combined with the infusion of CD34+ enriched donor bone marrow stem cells in an attempt to create a chimeric state and hence induce donor tolerance. This strategy was tested by evaluating graft survival following the removal of all immunosuppressive medication after one year.
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
- •Patients between 18 and 65 years of age
- •Patients with type 1 diabetes mellitus for more than 5 years duration
- •One or more of the following:
- •Hypoglycemia unawareness - judged by history of blood sugars <54 on glucometer without symptoms and/or hypoglycemic episodes requiring assistance from either family, glucagon administration or emergency services
- •Poor diabetes control (HbA1c>8% or >2 visits/yr to hospital for treatment of ketoacidosis) despite intensive insulin therapy
- •Progressive complications of type 1 diabetes mellitus
- •Body Mass Index (BMI) ≤26
排除标准
- •Untreated proliferative diabetic retinopathy;
- •HbA1C > 12%;
- •Insulin requirement > 1.0u/kg/d
- •Stimulated or basal C-peptide > 0.3 ng/ml
- •Creatinine clearance < 60 and/or serum creatinine consistently > 1.5mg/dl;
- •Macroalbuminuria > 300mg albumin in 24 hours
- •Presence of panel reactive antibodies > 20%;
- •Previous/concurrent organ transplantation (except failed islet cell transplantation);
- •Any medical condition requiring chronic use of steroids;
- •Malignancy or previous malignancy (except non-melanomatous skin cancer);
- •X-ray evidence of pulmonary infection;
- •Active infections;
- •Positive tuberculin test (unless proof of adequate treatment for latent tuberculosis can be provided)
- •Active peptic ulcer disease,
- •Gall stones and/or portal hypertension and/or hemangioma on liver ultrasound;
- •Serological evidence of HIV, HBV (HBsAg+ and/or HBcAb+ and/or HBsAb+ without evidence of vaccination), HTLV-1 or HCV;
- •Negative serology for Epstein Barr virus (EBV) or evidence of acute infection (IgM>IgG);
- •Abnormal liver function test;
- •Anemia (hemoglobin <12.0 g/dl);
- •Hyperlipidemia (fasting total cholesterol >240mg/dl and/or fasting triglycerides >200mg/dl and/or fasting LDL cholesterol>140mg/dl);
- •Body Mass Index above 26 and/or weight >80kg;
- •Prostate specific antigen (PSA) > 4 ng/ml;
- •Unstable cardiovascular status (including positive stress echocardiography if >age 35);
- •Active alcohol or substance abuse;
- •Sexually active females who are not: a) post-menopausal, b) surgically sterile, or c) not using an acceptable method of contraception (oral contraceptives, Norplant, Depo-Provera, and barrier devices are acceptable; condoms used alone are not acceptable);
- •Positive pregnancy test or intent for future pregnancy, or male subject's intent to procreate.
- •Any condition or any circumstances that makes it unsafe to undergo an islet cell transplant.
- •History of previous transplant or previous bone marrow infusion.
- •Persistent leucopenia (white blood cell count <3,000/mm3
结局指标
主要结局
The Achievement of Persistent Islet Function Following Cessation of Immunosuppression.
时间窗: for the duration of islet graft function
Immunosuppression was never discontinued. Patients elected to move to other trials to receive additional islet infusions. Since immunosuppression was never discontinued we were not able to evaluate the primary endpoint.
A Reduction or Absence of Rejection Episodes
时间窗: for the duration of islet graft function
Number of rejection episodes after transplantation. Immunosuppression was never discontinued. Patients elected to move to other trials to receive additional islet infusions. Since immunosuppression was never discontinued we were not able to evaluate the primary endpoint.
次要结局
- Number of Subjects With Basal C-peptide Greater Than 0.5 ng/ml(for the duration of islet graft function)
- Number of Subjects With Reduction of Severe Hypoglycemia and Improvement in Hypoglycemia Awareness(for the duration of islet graft function)
研究者
Rodolfo Alejandro
Professor of Medicine
University of Miami