TRIALNET NATURAL HISTORY

自然历史试验网

• 批准号: 7718706
• 负责人: DANIEL ESTEN HALE
• 金额: $ 0.55万
• 依托单位: UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-04-01 至 2008-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7718706
• 关键词: Acute; Addendum; Age; Alleles; American; Antibodies; Autoantibodies; B-Lymphocytes; Back; Biochemical; Blood; Blood specimen; C-Peptide; Categories; Cellular Immunity; Characteristics; Clinical; Collection; Computer Retrieval of Information on Scientific Projects Database; Consent; DNA; Data; Databases; Development; Diabetes Mellitus; Diagnosis; Eligibility Determination; Evolution; Funding; Future; Genetic Markers; Glucose; Glycosylated hemoglobin A; Grant; Hyperglycemia; IA-2 protein; Immune Tolerance; Immunologics; Incidence; Individual; Informed Consent; Institution; Insulin; Insulin-Dependent Diabetes Mellitus; Islet Cell; Islets of Langerhans; Laboratories; Learning; Measurement; Medical Records; Metabolic; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; Numbers; OGTT; Outcome; Outcome Study; Participant; Pathogenesis; Phase; Prevalence; Prevention; Procedures; Protocols documentation; Qualifying; Research; Research Personnel; Residual state; Resources; Risk; Risk Assessment; Sampling; Screening procedure; Site; Source; Test Result; Testing; Time; United States National Institutes of Health; Ursidae Family; Visit; Writing; base; cohort; demographics; design; follow-up; impaired glucose tolerance; intravenous glucose tolerance test; prospective; repository; sample collection

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. OBJECTIVE: The overall objective of this study is to perform baseline and repeat assessments over time of the metabolic and immunologic status of individuals at risk for Type 1 Diabetes (T1D) in order to a) characterize their risk for developing T1D; b) describe the pathogenic evolution of T1D; and c) to increase the understanding of the pathogenetics factors involved in the development of T1D. Specific objectives are: 1. To determine the risk for the occurrence of T1D according to oral glucose tolerance tests (OGTT), C-Peptide levels, biochemical autoantibodies (anti-GAD65, anti ICA52 and IAA), islet cell autoantibodies (ICA) markers of cell-mediated immunity, intravenous glucose tolerance tests (IVGTT), and HLA genetic markers that are associated with risk for T1D. 2. To examine the accuracy of TrialNet risk assessment procedures for predicting future T1D. 3. To determine the prevalence of impaired glucose tolerance and ICA posivity in individuals with at least one positive biochemical autoantibody test. 4. To characterize the progression of immunologic abnormalities in the development of the T1D by serially studying biochemical autoantibodies, ICA and markers of cell-mediated immunity. 5. To characterize the progression of metabolic decompensation in the development of T1D by serially studying insulin, C-peptide and glucose levels, and to identify immunologic and other factors associated with this decompensation. 6. To determine the incidence of severe acute metabolic decompensation as the initial clinical presentation in individuals who have been identified as being at increased risk for T1D. 7. To identify individuals who qualify for TrialNet prevention trials to T1D. 8. To accrue additional information about immunologic and metabolic factors related to the pathogenesis of T1D by analyzing stored blood samples. The Immune Tolerance Network will function as a core laboratory for TrialNet for the development of specialized immunologic procedures. 9. To accrue additional information about genetic markers associated with risk for the development of T1D by analyzing stored blood samples. 10. For those who participated in the DPT-1 study, to examine associations of characteristics (e.g. demographics, immunologc, metabolic, etc.) assessed during the DPT-1 study with characteristics and outcomes assessed in TrialNet. RESEARCH PLAN AND METHODS: The study is divided into three phases: Screening, Baseline Risk Assessment and Follow-up Risk Assessment. Each of these phases will require separate informed consent for entry. A prospective cohort design will be usd for the study. Phase 1 involves overall screening and measurements of biochemical autoantibodies (GAD65, ICA512 and mIAA) along with ICA to determine eligibility for the Phase 2 risk assessment. It is possible that individuals who do not qualify for Phase 2 might still be eligible for other TrialNet studies. Therefore, they may be contacted in the future so that they can be informed of these studies. In addition, they will be contacted periodically to learn if they have developed T1D. Individuals under the age of 18 years, who do not qualify for Phase 2, will be invited back for rescreening on an annual basis until they reach their 18th birthday. The baseline risk assessment will include an OGTT, the measurement of HbA1c, testing for autoantibodies, and HLA typing in consent participants. Participants with protective HLA alleles will not be excluded from this study. Upon completion of Phase 2, participants will be classified into one of three risk categories for the occurrence of T1D within five years: = 25%, and =50%. These categories are based on the OGTT results and number of confirmed positive antibodies. Participants will be informed of their risk categories when all test results are available. Individuals who participate in Phase 2 will also be offered the opportunity (through written consent) to enter Phase 3 for follow-up risk assessments. They will be seen at six month intervals for five years or until the end of the study. At each visit, procedures will include an OGTT, collection of blood for autoantibody testing and measurement of HbA1c levels. Although there will not be a formal categorization of risk following each assessment, participants will be informed of their test results upon request. During each phase of the sudy, residual blood samples and DNA samples in Phase 2 from consenting participants will be stored indefinitely at a TrialNet core laboratory and/or an NIDDK repository site for future immunologic and metabolic assessments that bear upon mechanisms of B-cell destruction and to obtain additional information about genetic markers associated with the risk for development of T1D. Subjects may still participate in all phases of the study even if they choose not to give consent for storage. Mechanistic samples will aso be collected at Phase 2 and 3 at designated sites (we are one) participating in the Mechanistic Addendum for Clinical Centers and Major Affiliates for the collection of samples for storage for mechanistic studies. Individuals who qualify for prevention trials based on their risk assessments will be invited to participate in those trials as they become available. Individuals who enter a prevention trial will be followed according to the protocol of that trial. However, pertinent data accrued during the trial (conditional upon treatment status in the trial) such as the development of T1D, may be incorporated into the database for study. The primary study outcome is diabetes mellitus (T1D) as defined by the American Diabetes Association (ADA) criteria. For most subjects, this will be based upon the results of an OGTT in the absence of symptomatic hyperglycemia. Confirmation of a diagnosis of diabetes by a second OGTT test in asymptomatic individuals will be required. Individuals who are hospitalized at diagnosis will be assessed through medical records.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 中心，不一定是研究者的机构。 目的：本研究的总体目标是对有 1 型糖尿病 (T1D) 风险的个体的代谢和免疫状态进行基线和随时间的重复评估，以便 a) 描述他们患 T1D 的风险； b) 描述 T1D 的致病演变； c) 增加对 T1D 发生的发病机制的了解。具体目标是： 1.根据口服葡萄糖耐量试验（OGTT）、C肽水平、生化自身抗体（抗GAD65、抗ICA52和IAA）、细胞介导的胰岛细胞自身抗体（ICA）标志物来确定发生T1D的风险免疫、静脉葡萄糖耐量试验 (IVGTT) 和与 1 型糖尿病风险相关的 HLA 遗传标记。 2. 检查 TrialNet 风险评估程序预测未来 T1D 的准确性。 3. 确定至少一项生化自身抗体检测呈阳性的个体糖耐量受损和 ICA 阳性的患病率。 4. 通过连续研究生化自身抗体、ICA 和细胞介导免疫标志物来表征 T1D 发展过程中免疫异常的进展。 5. 通过连续研究胰岛素、C 肽和葡萄糖水平来表征 T1D 发展过程中代谢失代偿的进展，并确定与这种失代偿相关的免疫学和其他因素。 6. 确定严重急性代谢失代偿的发生率，作为已被确定为 T1D 风险增加的个体的初始临床表现。 7. 确定符合 TrialNet 预防 T1D 试验资格的个人。 8. 通过分析储存的血液样本，获得与 T1D 发病机制相关的免疫和代谢因素的更多信息。 免疫耐受网络将作为 TrialNet 的核心实验室，用于开发专门的免疫程序。 9. 通过分析储存的血液样本，获得与 T1D 发生风险相关的遗传标记的更多信息。 10. 对于参与 DPT-1 研究的人员，检查 DPT-1 研究期间评估的特征（例如人口统计学、免疫学、代谢等）与 TrialNet 中评估的特征和结果之间的关联。 研究计划和方法：研究分为三个阶段：筛选、基线风险评估和后续风险评估。 每个阶段都需要单独的知情同意才能进入。 该研究将采用前瞻性队列设计。 第一阶段涉及生化自身抗体（GAD65、ICA512 和 mIAA）以及 ICA 的全面筛查和测量，以确定第二阶段风险评估的资格。 不符合第 2 阶段资格的个人可能仍有资格参加其他 TrialNet 研究。 因此，将来可能会联系他们，以便他们了解这些研究。 此外，我们还会定期联系他们，了解他们是否患有 T1D。 不符合第二阶段资格的 18 岁以下个人将被邀请每年重新进行筛查，直至年满 18 岁。 基线风险评估将包括 OGTT、HbA1c 测量、自身抗体测试以及同意参与者的 HLA 分型。 具有保护性 HLA 等位基因的参与者不会被排除在本研究之外。 第 2 阶段完成后，参与者将被分为五年内发生 T1D 的三个风险类别之一： = 25% 和 = 50%。 这些类别基于 OGTT 结果和确认的阳性抗体数量。 当所有测试结果可用时，参与者将被告知其风险类别。 参与第二阶段的个人还将有机会（通过书面同意）进入第三阶段进行后续风险评估。 他们将在五年内每隔六个月进行一次检查，或者直到研究结束。 每次就诊时，程序将包括 OGTT、采集血液进行自身抗体测试以及 HbA1c 水平测量。 尽管每次评估后不会有正式的风险分类，但参与者将根据要求获知其测试结果。 在研究的每个阶段中，来自同意参与者的残余血液样本和第 2 阶段的 DNA 样本将无限期存储在 TrialNet 核心实验室和/或 NIDDK 存​​储库站点，用于未来对 B 细胞破坏机制产生影响的免疫和代谢评估并获得有关与 1 型糖尿病发生风险相关的遗传标记的更多信息。 即使受试者选择不同意存储，他们仍然可以参与研究的所有阶段。 机械样本也将在第 2 和第 3 阶段在指定地点（我们是其中之一）收集，这些地点参与临床中心和主要附属机构的机械附录，用于收集样本用于机械研究的存储。 根据风险评估符合预防试验资格的个人将被邀请参加这些试验。 参加预防试验的个人将根据该试验的方案进行跟踪。 然而，试验期间积累的相关数据（以试验中的治疗状态为条件），例如 T1D 的发展情况，可以纳入数据库进行研究。 主要研究结果是美国糖尿病协会 (ADA) 标准定义的糖尿病 (T1D)。 对于大多数受试者，这将基于在没有症状性高血糖的情况下 OGTT 的结果。 需要对无症状个体进行第二次 OGTT 测试来确认糖尿病的诊断。 诊断时住院的个人将通过病历进行评估。