Treatment of Type I Diabetes by Islet Transplantation into the Gastric Submucosa
胃粘膜下层胰岛移植治疗 I 型糖尿病
基本信息
- 批准号:9273520
- 负责人:
- 金额:$ 48.98万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2014
- 资助国家:美国
- 起止时间:2014-05-01 至 2020-04-30
- 项目状态:已结题
- 来源:
- 关键词:AchievementAnimal ModelAntibodiesAntithymoglobulinAutoantibodiesAutoimmune ProcessBiological AssayBiopsyBloodBlood CirculationCellsCharacteristicsClinicalDNADonor SelectionEarly DiagnosisEndoscopyEngraftmentEnvironmentFunctional disorderGastric SubmucosaGraft RejectionHypoglycemiaHypoxiaImmuneImmune responseImmunologicsImmunosuppressionImmunosuppressive AgentsInflammationInflammatoryInflammatory ResponseInfusion proceduresInjection of therapeutic agentInjuryInsulinInsulin-Dependent Diabetes MellitusInterventionIslets of Langerhans TransplantationKidneyKidney TransplantationLeadLiver parenchymaLocationLymphocyte SubsetMeasurementMeasuresMediatingMetabolicMonitorOutcomeOxygenPancreas TransplantationPatientsPhysiologicalPreparationProceduresProcessProtocols documentationReactionRecruitment ActivityRegimenRenal functionSafetySamplingSerumSiteStandardizationSteroidsStomachSurgical complicationT-LymphocyteTNF geneTechnologyTestingTimeTransplantationUnited States National Institutes of HealthVenousbaseclinical research sitediabetic patientefficacy trialexperienceglycemic controlgraft functionimprovedimproved outcomeintravenous glucose tolerance testisletislet allograftkidney allograftloss of functionmetabolic abnormality assessmentminimally invasivenovelnovel strategiesprospectivepublic health relevancetype I diabetic
项目摘要
DESCRIPTION (provided by applicant): Pancreatic islet transplantation offers a minimally invasive approach to restore normoglycemia in type 1 diabetics while avoiding the hypoglycemic complications observed with intensive insulin therapy and the surgical complications associated with pancreas transplantation. Although significant progress has been made in clinical islet transplantation, overall outcomes remain suboptimal since many patients lose insulin independence a few years after transplantation and multiple donors are usually needed to achieve independence. The cause of this progressive loss of function is multifactorial, but mounting evidence suggests that much of the islet loss after transplant is directly related to the intraportal transplant site that is used in clinical islet transplantation. Intravascular infusion f the islets triggers a severe, non-specific inflammatory response (immediate blood-mediated inflammatory reaction, IBMIR) which destroys at least 50% of the islet mass. The engraftment of the surviving islets is further compromised by the relatively hypoxic portal venous environment, and the infused islets are exposed to potentially toxic levels of immunosuppressive agents being absorbed from the gut into the portal circulation. Together, these characteristics contribute to early as well as late loss of islet function after transplantation. The gastric submucosa is a newl described transplant site that can support islet engraftment while avoiding many of the drawbacks associated with intraportal infusion. In addition, this site is easily accessible via upper endoscopy and the submucosal injection procedure is safe and technically straightforward. The aim of this prospective, single-center trial is to provide initial clinical experience regarding the safety and efficacy of endoscopic gastric submucosal islet transplantation in type I diabetic patients with kidney allografts. A total of 6 patients will be recruited into the trial. We will follow the standardized islet manufacturing protocols and the thymoglobulin-based induction immunosuppressive regimen developed by the Clinical Islet Transplant consortium (CIT). Outcomes will include safety measures, glycemic control and insulin use, metabolic assessments of graft function, allo/auto-immune responses, and protocol biopsies to assess graft rejection/inflammation. We believe that this novel approach to islet transplantation has the potential to significantly improve current islet transplantation outcomes by enhancing islet engraftment and long-term function.
描述(由申请人提供):胰岛移植提供了一种微创方法来恢复1型糖尿病患者的正常血糖,同时避免了强化胰岛素治疗观察到的低血糖并发症和胰腺移植相关的手术并发症。尽管临床胰岛移植取得了显著进展,但总体结果仍然不理想,因为许多患者在移植后几年内失去了胰岛素依赖性,并且通常需要多个供体才能实现独立性。这种进行性功能丧失的原因是多因素的,但越来越多的证据表明,移植后的胰岛损失与临床胰岛移植中使用的门静脉内移植部位直接相关。胰岛的血管内输注触发严重的非特异性炎症反应(立即血液介导的炎症反应,IBMIR),其破坏至少50%的胰岛质量。存活胰岛的植入进一步受到相对缺氧的门静脉环境的损害,并且输注的胰岛暴露于从肠道吸收到门静脉循环中的潜在毒性水平的免疫抑制剂。总之,这些特征有助于移植后胰岛功能的早期和晚期丧失。胃粘膜下层是一种新的移植部位,它可以支持胰岛移植,同时避免了门静脉内输注的许多缺点。此外,该部位易于通过上消化道内窥镜进入,粘膜下注射程序安全且技术简单。这项前瞻性单中心试验的目的是提供关于内镜下胃粘膜下胰岛移植在I型糖尿病患者中的安全性和有效性的初步临床经验。本试验将共招募6例患者。我们将遵循标准化的胰岛制造方案和由临床胰岛移植联盟(CIT)开发的基于胸腺球蛋白的诱导免疫抑制方案。结果将包括安全性措施、血糖控制和胰岛素使用、移植物功能的代谢评估、同种/自身免疫反应和评估移植物排斥/炎症的方案活检。我们相信,这种新的胰岛移植方法有可能通过增强胰岛植入和长期功能来显着改善目前的胰岛移植结果。
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)
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Andrew Mark Posselt其他文献
Andrew Mark Posselt的其他文献
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{{ truncateString('Andrew Mark Posselt', 18)}}的其他基金
Treatment of Type I Diabetes by Islet Transplantation into the Gastric Submucosa
胃粘膜下层胰岛移植治疗 I 型糖尿病
- 批准号:
8843842 - 财政年份:2014
- 资助金额:
$ 48.98万 - 项目类别:
Treatment of Type I Diabetes by Islet Transplantation into the Gastric Submucosa
胃粘膜下层胰岛移植治疗 I 型糖尿病
- 批准号:
9479133 - 财政年份:2014
- 资助金额:
$ 48.98万 - 项目类别:
"Advancing Islet Transplant for Type 1 Diabetes Care"
“推进胰岛移植治疗 1 型糖尿病”
- 批准号:
8078323 - 财政年份:2010
- 资助金额:
$ 48.98万 - 项目类别:
"Advancing Islet Transplant for Type 1 Diabetes Care"
“推进胰岛移植治疗 1 型糖尿病”
- 批准号:
8133338 - 财政年份:2009
- 资助金额:
$ 48.98万 - 项目类别:
"Advancing Islet Transplant for Type 1 Diabetes Care"
“推进胰岛移植治疗 1 型糖尿病”
- 批准号:
7791012 - 财政年份:2009
- 资助金额:
$ 48.98万 - 项目类别:
Effect of Obesity on Long-Term Clinical Outcomes after Kidney Donation
肥胖对捐肾后长期临床结果的影响
- 批准号:
7589481 - 财政年份:2009
- 资助金额:
$ 48.98万 - 项目类别:
"Advancing Islet Transplant for Type 1 Diabetes Care"
“推进胰岛移植治疗 1 型糖尿病”
- 批准号:
7940817 - 财政年份:2009
- 资助金额:
$ 48.98万 - 项目类别:
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