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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此可以在其他清晰的条目中代表。列出的机构是 对于中心，这不一定是调查员的机构。 目的：这项研究的总体目的是对有T1D风险的个体的代谢和免疫学状态进行基线和重复评估： a）要表征他们发展T1D的风险， b）描述T1D的致病演化，并描述 c）增加对T1D发展中涉及的致病因素的理解。 概括： T1D发展的试验网络自然史研究分为三个阶段：筛查（阶段1），基线风险评估（第2阶段）和随访风险评估（第3阶段）。这些阶段中的每一个都需要单独的知情同意书才能进入。这项研究将使用前瞻性队列设计。 第1阶段涉及筛查与T1D相关的自身抗体的存在。在筛查期间在两个单独的血液样本上（即确认的自身抗体阳性）在两个单独的血液样本上对一个或多个相同的生化自身抗体呈阳性的个体将有资格进入研究第2阶段，该研究阶段的第2阶段是基线风险评估。此外，在筛查期间获得的第一个血液样本上至少有两个生化自身抗体为阳性的个体将有资格进入第2阶段。这些受试者将可以选择在第2阶段提供第二个样品以进行自身抗体确认或在第2阶段之前提供第二个样品。 由于试验网是一个联盟，它将继续开发用于研究T1D的病因和预防的方案，因此不符合第2阶段资格的个人可能仍然有资格参加其他研究。因此，将来可能会联系它们，以便可以将它们告知新研究。此外，将定期与他们联系，以了解他们是否已开发了T1D。 18岁以下的个人（不具备第二阶段的人）将被邀请回来每年重新分组，直到他们18岁生日。基线风险评估将包括OGTT，HBA1C的测量，ICA测试和HLA打字（同意参与者）。具有保护性HLA等位基因的参与者不会被排除在这项研究之外。在某些情况下，还将进行20分钟的IVGTT用于第一相胰岛素反应（FPIR）。 第2阶段完成后，将在五年内将参与者分为T1D发生的三个风险类别之一：小于25％，25-50％，大于50％。风险类别将根据OGTT结果定义，确认的阳性生化自身抗体数量，ICA阳性，并在需要时，IVGTT结果。当所有测试结果可用时，将向参与者告知他们的风险类别。 参加第2阶段的个人也将获得（通过书面同意）进入第3阶段的机会进行后续风险评估。它们将在六个月的间隔五年或直到研究结束时看到它们。在每次访问中，程序都将包括OGTT，用于自身抗体测试的血液收集以及HBA1C水平的测量。不会执行IVGTT。尽管每次评估后都不会对风险进行正式分类，但会根据要求将参与者告知其测试结果。 在研究的每个阶段中，同意参与者的残留血样（和第2阶段的DNA样本）将无限期地存储在试验网核实验室和/或NIDDK存储库站点中，以实现未来的免疫和代谢评估，以实现破坏机制，并获得有关与T1D相关风险相关的遗传标记的其他信息。即使受试者选择不同意存储，他们仍可能参与研究的所有阶段。机械样品还将在参与协议修订的临床中心的第2和3阶段收集，以收集用于机械研究的样品。 根据风险评估有资格获得预防试验的个人将被邀请参加这些试验。参加预防审判的个人将根据该审判的协议进行。但是，在试验期间（在试验中以治疗状况为条件）（例如T1D的发展）所产生的相关数据可以纳入本研究的数据库中。 主要的研究结果是美国糖尿病协会（ADA）标准所定义的糖尿病（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。将需要在无症状个体中通过第二次OGTT检验确认糖尿病的诊断。在诊断中住院的人将通过病历评估。