NATURAL HISTORY STUDY OF THE DEVELOPMENT OF TYPE I DIABETES

I 型糖尿病发展的自然史研究

• 批准号: 8166968
• 负责人: RICHARD E PRATLEY
• 金额: $ 0.77万
• 依托单位: UNIVERSITY OF VERMONT & ST AGRIC COLLEGE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-03-01 至 2011-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8166968
• 关键词: 18 year old; Alleles; Amendment; American; Autoantibodies; Back; Biochemical; Blood; Blood specimen; Categories; Clinical; Collection; Computer Retrieval of Information on Scientific Projects Database; Consent; DNA; Data; Databases; Development; Diabetes Mellitus; Diagnosis; Etiology; Evolution; Funding; Future; Genetic Markers; Glycosylated hemoglobin A; Grant; Hyperglycemia; Immunologics; Individual; Informed Consent; Institution; Insulin-Dependent Diabetes Mellitus; Laboratories; Learning; Measurement; Medical Records; Metabolic; National Institute of Diabetes and Digestive and Kidney Diseases; Natural History; OGTT; Outcome Study; Participant; Phase; 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; design; first phase insulin response; follow-up; intravenous glucose tolerance test; phase 2 study; 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 T1D in order: a) To characterize their risk for developing T1D, b) To describe the pathogenetic evolution of T1D, and c) To increase the understanding of the pathogenetic factors involved in the development of T1D. SUMMARY: The TrialNet Natural History Study of the Development of T1D is divided into three phases: Screening (Phase 1), Baseline Risk Assessment (Phase 2) and Follow-up Risk Assessments (Phase 3). Each of these phases will require separate informed consent for entry. A prospective cohort design will be used for the study. Phase 1 involves screening for the presence of autoantibodies associated with T1D. Individuals who are positive for one or more of the same biochemical autoantibodies (anti-GAD65, anti-ICA512 or IAA) on two separate blood samples during screening (i.e., confirmed autoantibody positive) will be eligible for entry into Phase 2 of the study, the baseline risk assessment. In addition, individuals who are positive for at least two biochemical autoantibodies on the first blood sample obtained during screening will be eligible for entry into Phase 2. These subjects will have the option of providing the second sample for autoantibody confirmation during Phase 2 or providing the second sample before proceeding to Phase 2. Since TrialNet is a consortium that will continue to develop protocols for studying the etiology and prevention of T1D, it is possible that individuals who do not qualify for Phase 2 might still be eligible for other studies. Therefore, they may be contacted in the future so that they can be informed of new 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 ICA, and HLA typing (in consenting participants). Participants with protective HLA alleles will not be excluded from this study. In certain cases, a 20 minute IVGTT for First Phase Insulin Response (FPIR) will also be performed. Upon completion of Phase 2, participants will be classified into one of three risk categories for the occurrence of T1D within five years: less than 25%, 25 - 50%, and greater than 50%. The risk categories will be defined according to the OGTT results, number of confirmed positive biochemical autoantibodies, ICA positivity, and when required, IVGTT results. 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. IVGTTs will not be performed. 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 study, 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 destruction, and to obtain additional information about genetic markers associated with risk for the 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 also be collected at Phases 2 and 3 at Clinical Centers participating in the Protocol Amendment 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 this 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 对于中心来说，它不一定是研究者的机构。 目的：本研究的总体目标是对 T1D 风险个体的代谢和免疫状态进行基线和重复评估，以便： a) 描述他们患 T1D 的风险， b) 描述 T1D 的发病机制演变，以及 c) 增加对 T1D 发病相关致病因素的了解。 概括： TrialNet 对 T1D 发展的自然史研究分为三个阶段：筛查（第 1 阶段）、基线风险评估（第 2 阶段）和后续风险评估（第 3 阶段）。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。 第一阶段涉及筛查是否存在与 T1D 相关的自身抗体。在筛查期间两个单独的血液样本中一种或多种相同生化自身抗体（抗 GAD65、抗 ICA512 或 IAA）呈阳性（即确认自身抗体阳性）的个体将有资格进入研究的第 2 阶段，即基线风险评估。此外，在筛查期间获得的第一份血液样本中至少有两种生化自身抗体呈阳性的个体将有资格进入第二阶段。这些受试者可以选择在第二阶段期间提供第二份样本以进行自身抗体确认，或在进入第二阶段之前提供第二份样本。 由于 TrialNet 是一个将继续开发研究 T1D 病因和预防方案的联盟，因此不符合第 2 阶段资格的个人可能仍有资格参加其他研究。因此，将来可能会联系他们，以便他们了解新的研究。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筛查，直到年满 18 岁。基线风险评估将包括 OGTT、HbA1c 测量、ICA 测试和 HLA 分型（在同意的参与者中）。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。在某些情况下，还将进行 20 分钟的 IVGTT 第一阶段胰岛素反应 (FPIR)。 第二阶段完成后，参与者将被分为五年内发生 T1D 的三个风险类别之一：低于 25%、25 - 50% 和高于 50%。风险类别将根据 OGTT 结果、确诊的生化自身抗体阳性数量、ICA 阳性以及需要时的 IVGTT 结果来定义。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。在五年内或直到研究结束之前，他们将每隔六个月进行一次检查。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。不会进行 IVGTT。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，来自同意的参与者的残留血液样本（以及第二阶段的 DNA 样本）将无限期地存储在 TrialNet 核心实验室和/或 NIDDK 存​​储库站点，用于未来对破坏机制进行免疫和代谢评估，并获取有关与 T1D 发展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。机械样本也将在参与议定书修正案的临床中心的第 2 和第 3 阶段收集，以收集样本用于机械研究的储存。 根据风险评估有资格参加预防试验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，可以纳入本研究的数据库中。 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。