Type 1 Diabetes-A Proposal for Prevention & Intervention

1 型糖尿病 - 预防建议

基本信息

批准号：
7938600
负责人：
Antoinette M. Moran
金额：
$ 89.14万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-30 至 2014-04-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7938600
关键词：
Ablation Academy Adult Adverse event Aftercare Animal Model Antibodies Antithymoglobulin Autologous Biological Preservation Blood Circulation Blood Component Removal C-Peptide Cells Clinical Collaborations Common Terminology Criteria for Adverse Events Community Health Cyclic GMP Data Dose Enrollment Family Physicians Family Practice Future Goals Hospitals Hour Human Immunologic Tests Immunologics Infusion procedures Insulin-Dependent Diabetes Mellitus Intervention Trial Leukapheresis Maximum Tolerated Dose Methodology Methods Minnesota Molecular Monitor Natural History Oryctolagus cuniculus Patients Pharmaceutical Preparations Phase Phase I Clinical Trials Preventive Intervention Principal Investigator Procedures Protocols documentation Regulatory T-Lymphocyte Research Residual state Safety Severities Site T-Lymphocyte Terminology Therapeutic Time Universities arm cohort improved leukemia peripheral blood programs treatment effect

项目摘要

DESCRIPTION (provided by applicant): The University of Minnesota is one of the original 14 US TrialNet centers. We have implemented 8 protocols to date. Our particular strength has been enrollment in prevention and intervention trials, where we are the number 1 overall recruiter. Our recruitment in the Natural History Study (NHS), however, has been average. In order to improve this, we have embarked on a new collaboration with Dr. Kevin Peterson, Director of Research for the UM Department of Family Medicine and Community Health and Director of the Minnesota Academy of Family Physicians Research Network. We anticipate access immediately to more than 1000 patients with T1D, with increased future access as this network grows. In this application we are proposing therapy with autologous Tregulatory cells (Tregs). Previous protocols have attempted to increase endogenous Treg numbers with drugs. Tregs themselves have not previously been available in sufficient numbers for clinical use. Our group is the first to develop a clinically applicable selection and culture method for manufacturing large numbers of Tregs from peripheral blood. Preliminary data in animal models and in humans with leukemia suggest that this product is safe. This is a single site, single arm phase 1 dose escalation trial. Adult subjects with recent (3-12 months) onset T1D and persistent C-peptide secretion will receive an infusion of autologous peripheral blood- derived Tregs (CD4+/CD25+/FoxP3+) using new methodology developed at the UM Molecular and Cellular Therapeutics cGMP Facility. Cells will be collected by leukapheresis and expanded in culture for up to 35 days and then cryopreserved. Immediately following leukapheresis, subjects will receive a course of thymoglobulin, 4 doses over 1 week. Thawed, autologous Tregs will be infused approximately 2 months later, at a time when there is no residual detectable rabbit antibody in the circulation. Safety and immunologic data and C-peptide secretion will be followed for 2 years. The long-term goal is to gather preliminary data in anticipation of an intervention trial of peripheral-blood derived autologous CD4+/CD25+/FoxP3+ treatment of new onset T1D.

描述（由申请人提供）：明尼苏达大学是最初的14个美国试验中心之一。迄今为止，我们已经实施了8个协议。我们的特殊优势是进入预防和干预试验，我们是第一名的总招聘人员。但是，我们在自然史研究（NHS）中的招募是平均水平。为了改善这一点，我们已经与UM家庭医学和社区健康部研究主任兼明尼苏达州家庭医师研究网络的主任Kevin Peterson博士进行了新的合作。我们预计会立即访问1000多名T1D患者，随着该网络的增长，未来访问会增加。在此应用中，我们提议使用自体内treg菌细胞（TREG）进行治疗。以前的方案试图用药物增加内源性Treg数量。 Tregs本身以前没有足够的临床用途。我们的小组是第一个开发一种临床适用的选择和培养方法，用于从外周血制造大量Treg。动物模型和患有白血病的人类中的初步数据表明该产品是安全的。这是一个单位，单臂1剂量升级试验。使用UM分子和细胞疗法CGMP设施中开发的新方法，具有最近（3-12个月）发作T1D和持续C肽分泌的成年受试者将接受自体外周血衍生的Treg（CD4+/CD25+/FOXP3+）的输注。细胞将通过白细胞术收集，并在培养中扩展长达35天，然后冷冻保存。白细胞术后，受试者将立即获得胸腺球蛋白的疗程，其中1周超过1周。大约2个月后，在循环中没有残留的可检测到的兔抗体的情况下，解冻的，自体的Treg将被注入。安全性和免疫学数据和C肽分泌将持续2年。长期目标是收集初步数据，以预期对周围自体CD4+/CD25+/FOXP3+新发作T1D处理的干预试验。