NEW ONSET OF TYPE 1 DIABETES MYCOPHENOLATE MOFETIL-DACLIZUMAB CLINICAL TRIAL

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在过去的10 - 20年里，大量的证据表明，人类的1型糖尿病是一种慢性的、缓慢进展的自身免疫性疾病。本研究的目的是确定免疫干预策略，以防止1型糖尿病发病时β细胞破坏的进展。至少一些β细胞的持续存在将改善糖尿病的长期护理，不仅可以预防疾病本身的并发症，还可以预防低血糖，这是糖尿病治疗的结果。目的是阻止新糖尿病患者的β细胞破坏，因为一旦自身免疫过程进展到完全或接近完全破坏β细胞，免疫调节可能无法单独发挥作用。这项研究的基本原理是证明在为期4年的研究过程中，胰岛功能得到了有意义的保护，免疫系统的副作用最小。如果结果足够积极，该临床试验的数据可以作为更大规模试验的基础，或者可以建议进行其他联合干预试验，这些试验可能获得更好的疗效或可能在不需要持续免疫抑制的情况下保留c肽。长期糖尿病的并发症和成本是众所周知的，目前糖尿病并发症的成本每年超过1000亿美元。如果干预能够恢复正常胰岛功能，维持胰岛素的产生，将显著改善糖尿病代谢控制的预后，从而减少长期并发症。本研究还将检查拟议的治疗对免疫效应和免疫结果的替代标记物的影响。免疫反应的调节可以降低自身抗体滴度，减少或阻止自身抗原t细胞反应的产生。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The great body of evidence developed over the last 10 ¿ 20 years suggests that type 1 diabetes in humans is a chronic, slowly progressive autoimmune disease. The objective of this study is to identify immune intervention strategies that will prevent the progression of beta cell destruction from the time of onset of type 1 diabetes. The persistence of at least some beta cells should improve long-term diabetes care and prevent not only complications of the disease itself but also hypoglycemia, which is a consequence of its management. The aim is to arrest beta cell destruction in newly diabetic subjects because immune modulation may not work well alone once the autoimmune process has progressed to complete or near complete destruction of beta cells. The study¿s rationale is to demonstrate a meaningful preservation of islet function with minimal immune system side effects over the 4-year course of this study. The data from this clinical trial could serve as the basis for a larger trial if the results are sufficiently positive, or they could suggest other combined intervention trials that might achieve either better efficacy or potentially preserve C-peptide without the need for continued immunosuppression. The complications and costs of long-term diabetes are well known and the costs of diabetes complications are currently greater than $100 billion a year. An intervention, which could restore normal islet function and maintain production of insulin would significantly improve the prognosis for metabolic control of diabetes and thus reduce long-term complications. This study will also examine the effect of the proposed treatment on surrogate markers for immunologic effects and immunological outcomes Modulation of the immune response could lower autoantibody titers and either reduce or prevent the generation of autoantigenic T-cell responses.