Improving Medication Adherence in children who had a Liver Transplant: iMALT

这份申请使用了NIDDK的规划(U34)拨款机制。它是由Leading提交的 儿科移植中心作为多中心努力的下一步，以验证标记物的有效性 移植后未坚持服用免疫抑制药物(药物依从性 肝移植后，麦芽，多点研究)。不坚持服用免疫抑制剂是 青少年器官移植受者器官排斥的主要原因。本提案的目的是 是计划一项多点研究，调查量身定制的遥测干预措施，以改善 通过改善移植效果(减少发生排斥反应的患者数量) 接受肝脏移植的青少年坚持用药。这项研究将使用 用药水平变异性指数(MLVI)作为干预的靶点。MLVI是一种创新的 粘附性生物标记物，计算免疫抑制剂之间的变异性程度 药物随时间变化的血液水平(变异性越大=依从性越差)。它是一个强有力的预测者 器官排斥反应。将使用以下方法识别未遵守的高危青少年肝移植接受者 MLVI(MLVI和GT；2表示有临床意义的粘连)。遥测干预 (通过电话、FaceTime®或Skype®界面管理)将使经验丰富的 干预者从远程位置使用结构化、量身定制的 适应特定患者需求的方法。该方法包括寻址 心理回避与自我照顾有关，还包括提醒和问题- 解决已确定的遵守障碍。最终的研究--一项随机对照试验-- 将只接触有风险的患者，将通过MLVI标记物持续监测他们的进展， 并将根据两年试验期间的依从性监测结果量身定做干预措施 句号。这项研究将调查一种创新的“个性化医疗”方法，以针对 远程干预的努力。已经做了大量的前期工作，包括干预 试行；规划授权期将用于最后确定协议要素、成果措施 定义、管理和人体研究文件和批准，以及培训 所有地点的人员。

This submission uses the NIDDK's planning (U34) grant mechanism. It is submitted by leading pediatric transplant centers as the next step of a multicenter effort to validate a marker for nonadherence to immunosuppressant medications post-transplant (the Medication Adherence after Liver Transplant, MALT, multisite study). Nonadherence to immunosupressants is the leading cause of organ rejection in adolescent transplant recipients. The present proposal's aim is to plan a multisite study that will investigate a tailored telemetric intervention to improve transplant outcomes (reduce the number of patients who have a rejection) by improving adherence to medications in adolescents who had a liver transplant. This study will use the Medication Level Variability Index (MLVI) to target the intervention. The MLVI is an innovative biomarker of adherence which calculates the degree of variability between immunosuppressant medication blood levels over time (higher variability = worse adherence). It is a robust predictor of organ rejection. Nonadherent at-risk adolescent liver transplant recipients will be identified using the MLVI (MLVI>2 denotes clinically significant nonadherence). The telemetric intervention (administered via telephone, FaceTime ® or Skype ® interfaces) will enable experienced interventionists to address nonadherence from a remote location, using a structured, tailored approach that accommodates specific patient needs. This approach includes addressing psychological avoidance associated with self-care, and further includes reminders and problem- solving of identified barriers to adherence. The resulting study – a randomized controlled trial – will engage at-risk patients only, will continually monitor their progress through the MLVI marker, and will tailor the intervention to the adherence monitoring findings throughout the 2 year trial period. This study will investigate an innovative “personalized medicine” approach to target a remote intervention effort. Substantial preliminary work has been done including intervention pilots; the planning grant period will be used to finalize protocol elements, outcome measures definitions, regulatory and human subjects study documents and approvals, and training of personnel at all sites.