TrialNet: University of Florida Clinical Center and Network

描述(由申请人提供)：佛罗里达大学打算继续作为国家组成的糖尿病试验网络(1型糖尿病试验网络)的一部分作为临床中心，以最终研究旨在预防或延缓1型糖尿病(T1D)发展的疗法。佛罗里达大学临床中心参与了9项获得批准的NIH TrialNet方案，包括自然史研究、霉酚酸酯(MMF)/Dacluzimab(DZB)试验、抗CD20试验、CTLA-4 LG试验、口服胰岛素研究、比较混合膳食耐量(MMTT)-胰升糖素刺激(GST)C肽研究、T细胞分析验证研究、预防糖尿病的营养干预(NIP)研究和T1D遗传学联合体。该中心在招募受试者和进行TrialNet(和其他类型1研究)方面一直是表现最好的机构之一，并将继续努力监督其成功的附属中心网络和参与TrialNet研究招募和后续行动的参与医生，并进一步扩大这些努力。我们打算继续在新近发病的糖尿病患者中进行研究，旨在保护贝塔细胞功能和/或减少贝塔细胞破坏，如果证明是安全和有效的，则使用这些药物进行旨在预防疾病的研究。基于(I)在NOD小鼠中联合使用低剂量抗胸腺细胞球蛋白(ATG)和粒细胞集落刺激因子(GCSF)的激动人心的初步数据(疗效、机制和安全性)，(Ii)在其他人类自身免疫性疾病和移植方面的令人鼓舞的数据，(Iii)在新发患者中分别使用两种药物的试点研究，我们提议进行一项研究，旨在确定该组合作为一种干预措施，减缓新诊断的T1D患者的疾病进展的安全性、有效性和机制。 公共卫生相关性：1型糖尿病在全球范围内的发病率正在增加，这种疾病对受影响的个人和社会都是一个巨大的负担。佛罗里达大学临床中心将在TrialNet的框架内进行研究，以研究旨在(I)预防或延缓易患1型糖尿病患者的1型糖尿病发展的疗法(Ii)保护已确诊糖尿病患者的胰岛β细胞功能(Iii)了解导致胰岛素产生细胞被破坏的免疫学机制。

DESCRIPTION (provided by applicant): The University of Florida intends to continue as a Clinical Center as part of the nationally constituted diabetes trial network (Type 1 Diabetes TrialNet), in order to ultimately study therapies aimed at preventing or delaying the development of type 1 diabetes (T1D). The University of Florida Clinical Center has participated in nine approved NIH TrialNet protocols including the Natural History Study, the Mycophenolate Mofetil (MMF) / Dacluzimab (DZB) Trial, the Anti-CD20 Trial, the CTLA-4 lg Trial, the Oral Insulin Study, the comparative Mixed Meal Tolerance (MMTT) - Glucagon Stimulation (GST) C-peptide Study, the T-Cell Assay Validation Study, the Nutrition Intervention to Prevent Diabetes (NIP) Study, and the T1D Genetics Consortium. The Center has consistently been one of the strongest performers both in the recruitment of subjects and the conduct of TrialNet (and other Type 1 studies) and will work to continue oversight of its successful network of Affiliate Centers and participating physicians involved in TrialNet study recruitment and follow-up and to further expand these efforts. We intend to continue to conduct studies in patients with recent-onset diabetes aimed at preserving beta cell function and/or decreasing beta cell destruction, and, if safety and efficacy is demonstrated, implement studies using these agents aimed at the prevention of the disease. Based on (i) exciting preliminary (efficacy, mechanistic and safety) data using a combination of low-dose Anti-Thymocyte Globulin (ATG) and Granulocyte Colony Stimulating Factor (GCSF) in NOD mice, (ii) encouraging data in other human autoimmune disorders and transplantation (iii) pilot studies using each agent separately in new-onset patients, we propose to conduct a study aimed at establishing the safety, efficacy and mechanism of this combination as an intervention to slow disease progression in individuals with newly-diagnosed T1D. PUBLIC HEALTH RELEVANCE: The incidence of Type 1 diabetes is increasing worldwide and the disease is a tremendous burden on both afflicted individuals and society. Studies will be conducted by the University of Florida Clinical Center within the TrialNet umbrella to study therapies aimed at (i) preventing or delaying the development of type 1 diabetes in susceptible individuals (ii) preserving pancreatic islet beta cell function in patients with already established diabetes (iii) understanding the immunologic mechanisms leading to the destruction of the insulin producing cells.