TRIALNET SCREENING TO ASSESS RISK OF TYPE 1 DIABETES
用于评估 1 型糖尿病风险的试验网筛查
基本信息
- 批准号:7605176
- 负责人:
- 金额:$ 3.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-02-15 至 2007-11-30
- 项目状态:已结题
- 来源:
- 关键词:AdolescentAgeAntigensAutoantibodiesCanadaCellular ImmunityChildClinicalClinical TrialsComputer Retrieval of Information on Scientific Projects DatabaseConditionDeteriorationDevelopmentDiabetes MellitusDiabetes preventionDiseaseDoseEnrollmentEnvironmental Risk FactorEpidemiologic StudiesFundingFutureGeneticGrantImmunologicsIncidenceIndividualInstitutionInsulinInsulin-Dependent Diabetes MellitusIslet CellIslets of LangerhansJournalsLearningMedicineMetabolicModelingMonozygotic twinsNational Institute of Diabetes and Digestive and Kidney DiseasesNatural HistoryNew EnglandOralParticipantPathogenesisPatientsPreventionPrevention strategyProcessPublishingRelative (related person)ResearchResearch DesignResearch PersonnelResourcesRiskSamplingScreening procedureSiteSourceStagingStructure of beta Cell of isletTestingThinkingUnited StatesUnited States National Institutes of HealthVirus Diseasesbaseinterestnon-diabeticpreventprograms
项目摘要
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.
Type 1 diabetes mellitus (T1D) is a disease that results from the destruction of pancreatic beta-cells. It can occur at any age, but its incidence is highest in children and adolescents. Although all people are susceptible, relatives of individuals are at a much greater risk for T1D.
It is clear that genetic factors contribute to most cases of T1D. HLA-associated antigens have been found to be strongly predictive of T1D. However, environmental factors also appear to contribute to the disorder. Although identical twins of T1D patients are at very high risk, many never develop the condition. Also, some epidemiologic studies have suggested that other factors such as viral infections may be involved in the pathogenesis of T1D.
It is thought that the pathogenesis for most cases of T1D involves the immunologic destruction of pancreatic beta-cells. There is good evidence that cell-mediated immunity contributes to this. In addition, most patients who develop T1D have at least one autoantibody to islet cell antigens. These autoantibodies include ICAs, GAD65, IAA, and IA2 autoantibodies. Relatives of T1D patients who develop these autoantibodies are at greater risk for T1D than relatives negative for autoantibodies and the risk becomes greater when subtle metabolic abnormalities are evident even within the nondiabetic state.
There has been recent interest in the possibility that T1D is preventable. The elucidation of the mechanisms of its pathogenesis suggests that manipulations of the immunologic milieu could disrupt the disease process. In addition, prevention trials have become more feasible because it is now possible to identify individuals who are at high risk for T1D.
The Diabetes Prevention Trial-Type 1 (DPT-1) study was one of the first large-scale prevention trials of T1D. The aim of this trial was to study whether either low dose parenteral insulin or oral insulin administration would prevent the development of T1D. Relatives of patients with T1D were screened for the presence of autoantibodies associated with T1D. Those with autoantibodies were then staged through HLA and metabolic testing to determine whether subtle abnormalities were present that would increase the risk for T1D. Individuals who met criteria were offered entry in the clinical trial. Those at greater risk were eligible for enrollment in the parenteral insulin study, while those at lower risk were offered enrollment in the oral insulin study.
The parenteral insulin trial was recently completed and its findings published in the New England Journal of Medicine. (Diabetes Prevention Trial - Type 1 Diabetes Study Group. Effects of Insulin in Relatives of Patients with Type 1 Diabetes Mellitus. NEJM 2002; 346:1685-91.)
The oral insulin study continues. Although it was disappointing that there was no evidence of an insulin effect in the parenteral insulin trial, a great deal was learned from this study. Much information was ascertained about the natural history of the development of T1D. Importantly, the findings from DPT-1 confirmed that the incidence of T1D could be accurately predicted on the basis of autoantibody and HLA testing and metabolic staging.
Because of the continuing interest in the prevention of T1D, the NIDDK has provided funding to 14 centers to build a consortium (TrialNet) of investigators to develop and perform prevention trials. The rationale was that this group of experts in the field would facilitate the implementation of such studies. In addition to performing studies of individuals at high risk for T1D, TrialNet will also perform studies of individuals with new-onset diabetes. These studies will examine strategies for the prevention of further metabolic deterioration in those patients.
The TrialNet screening process for studies of high risk individuals will be modeled after that for DPT-1. The accrual of participants for DPT-1 required a massive program to screen for autoantibody positive relatives of patients with T1D. This necessitated the development of a network of Clinical Centers, Affiliate Sites and Satellite Sites throughout the United States and Canada. Over 100,000 relatives had screening samples collected. Most of these sites will participate in TrialNet screening.
The specific prevention studies are currently being developed. However, the screening program will be needed in the interim to identify potential participants for future prevention studies. Individuals who screen positive for autoantibodies will be offered participation in a Natural History Study if a prevention trial is not yet available to them. The screening program described herein represents the first step in the process of implementing the TrialNet prevention studies for T1D.
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。子项目及
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。
1 型糖尿病 (T1D) 是一种因胰腺 β 细胞破坏而导致的疾病。 它可发生于任何年龄,但以儿童和青少年发病率最高。 尽管所有人都易感,但个人的亲属患 T1D 的风险要大得多。
很明显,大多数 T1D 病例都是遗传因素造成的。研究发现 HLA 相关抗原可以强烈预测 T1D。 然而,环境因素似乎也导致了这种疾病。尽管 T1D 患者的同卵双胞胎面临很高的风险,但许多人从未患上这种疾病。 此外,一些流行病学研究表明,病毒感染等其他因素可能参与 T1D 的发病机制。
人们认为大多数 T1D 病例的发病机制涉及胰腺 β 细胞的免疫破坏。 有充分的证据表明细胞介导的免疫对此有贡献。此外,大多数患有 T1D 的患者至少有一种针对胰岛细胞抗原的自身抗体。 这些自身抗体包括 ICA、GAD65、IAA 和 IA2 自身抗体。 产生这些自身抗体的 T1D 患者的亲属比自身抗体阴性的亲属患 T1D 的风险更大,并且即使在非糖尿病状态下,当轻微的代谢异常明显时,风险也会更大。
最近人们对 T1D 是否可以预防的可能性产生了兴趣。 其发病机制的阐明表明,免疫环境的操纵可以破坏疾病过程。 此外,预防试验变得更加可行,因为现在可以识别 T1D 高危人群。
糖尿病预防试验 1 型 (DPT-1) 研究是首批大规模预防 T1D 试验之一。 该试验的目的是研究低剂量肠外胰岛素或口服胰岛素是否可以预防 1 型糖尿病的发生。 对 1 型糖尿病患者的亲属进行了筛查,以确定是否存在与 1 型糖尿病相关的自身抗体。 然后通过 HLA 和代谢测试对那些具有自身抗体的人进行分期,以确定是否存在会增加 T1D 风险的细微异常。 符合标准的个人被邀请参加临床试验。 那些风险较高的人有资格参加肠外胰岛素研究,而那些风险较低的人则有资格参加口服胰岛素研究。
肠外胰岛素试验最近完成,其研究结果发表在《新英格兰医学杂志》上。 (糖尿病预防试验 - 1 型糖尿病研究组。胰岛素对 1 型糖尿病患者亲属的影响。NEJM 2002;346:1685-91。)
口服胰岛素研究仍在继续。 尽管令人失望的是,在肠外胰岛素试验中没有证据表明胰岛素有作用,但从这项研究中我们学到了很多东西。 关于 T1D 发展的自然史的大量信息已确定。 重要的是,DPT-1 的研究结果证实,可以根据自身抗体、HLA 检测和代谢分期准确预测 T1D 的发病率。
由于人们对预防 T1D 的持续关注,NIDDK 已向 14 个中心提供资金,以建立一个研究人员联盟 (TrialNet),以开发和开展预防试验。 理由是该领域的专家组将促进此类研究的实施。 除了对 T1D 高危人群进行研究外,TrialNet 还将对新发糖尿病患者进行研究。 这些研究将探讨预防这些患者代谢进一步恶化的策略。
用于高风险个体研究的 TrialNet 筛选过程将仿照 DPT-1 的筛选过程。 DPT-1 参与者的增加需要一个大规模的计划来筛查 T1D 患者的自身抗体阳性亲属。 这就需要在美国和加拿大建立一个由临床中心、附属站点和卫星站点组成的网络。 收集了超过 100,000 名亲属的筛查样本。 大多数这些网站将参与 TrialNet 筛选。
目前正在开展具体的预防研究。 然而,在此期间需要进行筛查计划,以确定未来预防研究的潜在参与者。 如果尚未进行预防试验,则自身抗体筛查呈阳性的个人将有机会参加自然历史研究。 本文描述的筛查计划是实施 TrialNet T1D 预防研究过程中的第一步。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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DARRELL M WILSON其他文献
DARRELL M WILSON的其他文献
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{{ truncateString('DARRELL M WILSON', 18)}}的其他基金
CLINICAL TRIAL: ORAL INSULIN IN RELATIVES AT RISK FOR TYPE I DIABETES MELLITUS
临床试验:有 I 型糖尿病风险的亲属口服胰岛素
- 批准号:
7717928 - 财政年份:2007
- 资助金额:
$ 3.34万 - 项目类别:
CLINICAL TRIAL: TRIAL OF METFORMIN IN OBESE ADOLESCENTSMETFORMIN IN OBESE ADOL
临床试验:二甲双胍治疗肥胖青少年的试验二甲双胍治疗肥胖青少年的试验
- 批准号:
7717854 - 财政年份:2007
- 资助金额:
$ 3.34万 - 项目类别:
CLINICAL TRIAL: RITUXIMAB ON THE PROGRESSION OF TYPE 1 DIABETES IN NEW ONSET SUB
临床试验:利妥昔单抗对新发亚型 1 型糖尿病进展的影响
- 批准号:
7717894 - 财政年份:2007
- 资助金额:
$ 3.34万 - 项目类别:
CLINICAL TRIAL: TYPE 1 DIABETES: CELLCEPT ALONE OR IN COMBINATION WITH DACLIZUMA
临床试验:1 型糖尿病:单独使用 CELLCEPT 或与 DACLIZUMA 联用
- 批准号:
7717847 - 财政年份:2007
- 资助金额:
$ 3.34万 - 项目类别:
RECENT ONSET TYPE-1 DIABETES MELLITUS STUDY OF USING FRESH BLOOD SAMPLES
使用新鲜血液样本进行新近发病的 1 型糖尿病研究
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7605236 - 财政年份:2007
- 资助金额:
$ 3.34万 - 项目类别:
CLINICAL TRIAL: TRIALNET SCREENING TO ASSESS RISK OF TYPE 1 DIABETES
临床试验:评估 1 型糖尿病风险的试验网筛查
- 批准号:
7717853 - 财政年份:2007
- 资助金额:
$ 3.34万 - 项目类别:
EFFECTS OF RITUXIMAB ON THE PROGRESSION OF TYPE 1 DIABETES
利妥昔单抗对 1 型糖尿病进展的影响
- 批准号:
7605244 - 财政年份:2007
- 资助金额:
$ 3.34万 - 项目类别:
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