TrialNet: University of Florida Clinical Center and Network

TrialNet：佛罗里达大学临床中心和网络

• 批准号: 8288867
• 负责人: DESMOND Arthur SCHATZ
• 金额: $ 46.78万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 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/8288867
• 关键词: Activities of Daily Living; Antigens; Antithymoglobulin; Autoantibodies; Autoimmune Diseases; B-Lymphocytes; Beta Cell; Biological Assay; Blood Glucose; C-Peptide; CSF3 gene; Candida; Cell physiology; Cells; Clinical; Combined Modality Therapy; Comparative Study; Data; Dendritic Cells; Development; Diabetes Mellitus; Dietary Intervention; Disease; Disease Progression; Dose; Florida; Flow Cytometry; Frequencies; Glucagon; Glutamate Decarboxylase; Granulocyte Colony-Stimulating Factor; Human; IA-2-autoantibody; Immune response; Immunity; Immunization; Immunologics; Inbred NOD Mice; Incidence; Individual; Insulin; Insulin-Dependent Diabetes Mellitus; Intervention; Islet Cell; Islets of Langerhans; MS4A1 gene; Metabolic; Monitor; Natural History; Newly Diagnosed; Oral; Patients; Physicians; Pilot Projects; Population; Principal Investigator; Production; Protocols documentation; Regulatory T-Lymphocyte; Research Design; Safety; Serum; Societies; T-Lymphocyte; Tetanus; Therapeutic Intervention; Transplantation; United States National Institutes of Health; Universities; Work; base; blood glucose regulation; cytokine; diabetes mellitus genetics; disorder prevention; follow-up; insulin secretion; islet; mycophenolate mofetil; peripheral blood; prevent; public health relevance; randomized placebo controlled trial; validation studies

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.

描述（由申请人提供）：佛罗里达大学打算继续作为一个临床中心，作为全国糖尿病试验网络（1型糖尿病试验网络）的一部分，以最终研究旨在预防或延缓1型糖尿病（T1D）发展的治疗方法。佛罗里达大学临床中心参与了9项获批的NIH TrialNet试验方案，包括自然史研究、霉酚酸酯(MMF) / Dacluzimab （DZB）试验、抗cd20试验、ctla - 4lg试验、口服胰岛素研究、比较混合膳食耐受性(MMTT) -胰高血糖素刺激（GST） c肽研究、t细胞测定验证研究、营养干预预防糖尿病（NIP）研究和T1D遗传学联盟。该中心在招募受试者和开展TrialNet（以及其他1型研究）方面一直是表现最好的中心之一，并将继续努力监督其成功的附属中心网络和参与TrialNet研究招募和随访的医生，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开展旨在保持β细胞功能和/或减少β细胞破坏的研究，并且，如果安全性和有效性得到证明，将使用这些药物进行旨在预防该疾病的研究。基于(i)在NOD小鼠中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）联合使用的令人兴奋的初步（疗效、机制和安全性）数据，（ii）在其他人类自身免疫性疾病和移植中令人鼓舞的数据，（iii）在新发病患者中分别使用每种药物的初步研究，我们建议开展一项旨在确定安全性的研究。这种联合干预减缓新诊断T1D患者疾病进展的疗效和机制。