Sitagliptin therapy to improve outcomes after islet autotransplantation.

描述(由申请人提供)：Melena Bellin，医学博士，明尼苏达大学儿科内分泌学部儿科助理教授。在这个岗位上，她75%的时间致力于胰岛移植领域以患者为导向的研究。这一职业发展奖期间的具体目标将包括：1)提高临床试验管理、免疫学和胰岛移植方面的知识；2)每年出版2篇同行评议的手稿；3)完成下文所述的临床试验；以及4)在本奖项的最后两年提交R系列研究拨款。 作为密歇根大学临床研究硕士项目的学生，贝林博士接受过以患者为导向的研究方面的正式培训。她一直是胰岛移植队列研究和小型非随机临床试验的联合研究员。在职业发展奖期间，她将通过在与她的研究相关的更具体领域进行正式培训，出席她所在领域的国内和国际会议，以及通过进行大型随机临床试验来建立这一基础。在项目导师安托瓦内特·莫兰博士的指导下，贝林博士将进行一项随机双盲对照试验，评估西格列汀在全胰腺切除和胰岛自体移植后对胰岛素独立性和胰岛功能的影响。该项目将有两个目标：1)确定全胰腺切除和胰岛自体移植后使用DPP-4抑制剂是否会增加受体获得胰岛素非依赖性的比例，2)评估术前胰岛功能测试是否与胰岛产量相关。尽管基于胰岛素的疗法已经在胰岛同种异体移植的非常小的非随机试验中使用，但这将是第一次在自体胰岛移植中研究这种疗法的大型随机研究。 研究项目将在糖尿病和胰岛移植研究领域经验丰富的导师和共同导师的指导下进行，这些导师包括安托瓦内特·莫兰博士、伯恩哈德·赫林博士和大卫·萨瑟兰博士。密歇根大学在胰岛移植方面的丰富经验使这里成为这一研究重点的理想环境。整个学术进展将通过与咨询委员会的定期会议进行监测。 公共卫生相关性：胰岛移植是治疗慢性胰腺炎和1型糖尿病的新兴新疗法。该项目将探索患者的特征和干预措施，以提高胰岛移植的成功率。

DESCRIPTION (provided by applicant): Melena Bellin, MD is an Assistant Professor in the Department of Pediatrics, Division of Pediatric Endocrinology, at the University of Minnesota (UM). In this position, she devotes 75% of her time to patient-oriented research in the field of islet transplantation. Specific goals during this career development award period will include: 1) improved knowledge in clinical trials management, immunology, and islet transplantation; 2) publication of 2 peer-reviewed manuscripts per year; 3) completion of a clinical trial as described below; and 4) submission of a R-series research grant in the last 2 years of this award. Dr. Bellin has had formal training in patient-oriented research as a student in the M.S. program in Clinical Research at UM. She has been a co-investigator in cohort studies and small non-randomized clinical trials in islet transplant. She will build upon this foundation during the career development award period through formal training in more specific areas related to her research, attendance at national and international conferences in her field, and by conducting a large randomized clinical trial. Under the guidance of Dr. Antoinette Moran, the project mentor, Dr. Bellin will conduct a randomized double-blinded controlled trial evaluating the effect of sitagliptin treatment following total pancreatectomy and islet autotransplant on insulin independence and islet function. This project will have two aims: 1) to determine if treatment with a DPP-4 inhibitor after total pancreatectomy and islet autotransplant increases the proportion of recipients achieving insulin independence, and 2) to evaluate whether preoperative tests of islet function correlate with islet yield. Although incretin-based therapies have been used in very small, non-randomized trials of islet allotransplantation, this will be the first large randomized study to investigate such a therapy in islet autotransplant. Research projects will be conducted under the guidance of a mentor and co-mentors experienced in the fields of diabetes and islet transplant research-- Dr. Antoinette Moran, Dr. Bernhard Hering, and Dr. David Sutherland. The extensive experience with islet transplants at UM makes this an ideal environment for this research focus. Overall scholarly progress will be monitored by regular meetings with an advisory committee. PUBLIC HEALTH RELEVANCE: Islet transplant is an emerging new treatment for chronic pancreatitis and type 1 diabetes mellitus. This project will explore patient characteristics and an intervention which may improve the success of islet transplant.