ILIAD

伊利亚德

• 批准号: 7607620
• 负责人: HERBERT L BONKOVSKY
• 金额: $ 0.03万
• 依托单位: UNIVERSITY OF CONNECTICUT SCH OF MED/DNT
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-04-01 至 2008-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7607620
• 关键词: Alanine Transaminase; Amoxicillin-Potassium Clavulanate Combination; Authorization documentation; Biological; Biological Specimen Banks; Blood; Blood specimen; Case Report Form; Causations; Cells; Characteristics; Clinical; Clinical Data; Compatible; Computer Retrieval of Information on Scientific Projects Database; Consent; Consent Forms; DNA; Databases; Diabetes Mellitus; Drug Delivery Systems; Enrollment; Etiology; Event; Excision; Failure; Freezing; Funding; Future; Gastroenterologist; Genomics; Goals; Grant; Health Insurance Portability and Accountability Act; Health Personnel; Health Professional; Hospitalization; Immune; Individual; Informed Consent; Injury; Institutes; Institution; International Normalized Ratio; Interview; Investigation; Kidney Diseases; Life; Liver; Liver Dysfunction; Lymphocyte; Mails; Marketing; Medical; Medical Records; Morbidity - disease rate; Patients; Persons; Pharmaceutical Preparations; Phenotype; Phenytoin; Physicians; Plasma; Population; Predisposition; Procedures; Protocols documentation; Purpose; Rate; Recontacts; Registries; Research; Research Design; Research Personnel; Resources; Serum; Shipping; Ships; Source; Specimen; Study Subject; Telephone; Time; United States National Institutes of Health; Universities; Upper Limit of Normal; Valproic Acid; abstracting; base; clinical research site; drug mechanism; experience; follow-up; interest; isoniazid; liver biopsy; mortality; patient registry; repository; total measurement Bilirubin

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. Background and Rationale: Drug induced liver injury (DILI) is the single most common reason for regulatory actions concerning drugs, including failure to gain approval for marketing, removal from the market place, and restriction of prescribing indications. DILI is also a significant cause of morbidity and mortality in many patient populations. To stimulate and facilitate research into DILI, the National Institute of Diabetes, Digestive and Kidney Diseases (NIDDK) has recently established the Drug-Induced Liver Injury Network (DILIN). One of the initial projects to be conducted by the network is to retrospectively establish a nationwide registry of patients who have suffered severe idiosyncratic liver injury associated with drugs (ILIAD), and to collect, immortalize and store serum, Deoxyribonucleic acid (DNA), and lymphocytes from these patients (hereafter referred to as the "ILIAD protocol"). This ILIAD protocol will serve as a resource for subsequent mechanistic investigations of the basis for susceptibility to severe idiosyncratic DILI. Specific Aims and Objectives: The primary goal of the ILIAD protocol is to create: (a) a clinical database consisting of individuals who have experienced severe DILI caused by four specific drugs, and the relevant clinical data concerning the episode of DILI; and, (b) to create a bank of biological specimens obtained from these individuals. Corresponding information from control subjects will also be collected. These biological specimens will be DNA, plasma, and immortalized lymphocytes. Immortalized lymphocytes will provide unlimited amounts of genomic DNA for study as well as living immune cells for phenotyping studies. A secondary goal of the ILIAD protocol is to maintain a registry of cases in the ILIAD database so that they may be recontacted in the future. It is expected that this will facilitate additional studies exploring the mechanisms of DILI. Targeted Drugs: The initial drugs to be targeted in the ILIAD protocol are isoniazid (INH), phenytoin, clavulanic acid / amoxicillin (Augmentin and valproic acid. For INH, phenytoin, or clavulanic acid / amoxicillin, severe liver injury is defined as a documented serum total bilirubin > 2.5 mg/dl; for valproic acid, the criteria are compatible symptomatic clinical presentation that is severe enough to prompt hospitalization and evidence of liver dysfunction International normalized ratio (INR) > 1.5 or Alanine transaminase (ALT) > 3 X Upper Limit of Normal (ULN), and/or characteristic liver biopsy). The target drugs were chosen because they cause severe DILI at a high rate compared with other drugs, making our target enrollment for each drug (n = 50-100) attainable. In addition, these drugs are frequently administered to reasonably healthy patients not concurrently receiving other drugs more likely to be hepatotoxic, facilitating causation assessment. Basic Study Design: The five DILIN clinical centers will identify and contact patients at their own and affiliated institutions who may have suffered a liver injury due to one of the targeted drugs. They will also contact gastroenterologists, hepatologists, and other health care professionals most likely to have treated DILI cases. In the latter case, an information packet will be sent by the treating physician to the potential subject, and interested subjects will be requested to contact one of the five clinical sites. In either case, the subject will be given a brief description of the study's purpose and procedures, and when further interest in the study is expressed, s/he will be mailed provided with an information packet including the informed consent document, The Health Insurance Portability and Accountability Act (HIPAA) authorization and release of medical record forms. Once these documents have been received reviewed by the subject, study staff will contact the potential subject by telephone a second time. This follow-up contact will either occur by telephone or in person at the subject's convenience. Informed consent will be obtained, and if this occurs over the telephone, it will be witnessed by a third party on the line. Then, requisite information will be collected using a telephone or personal interview format. Prior to ending this phone call the end of the second contact, the subject will be asked to sign the consent, HIPAA authorization, and release of medical information forms and return provide them to the DILIN clinical site. Arrangements for blood drawing will be made. The blood sample will be shipped to the Rutgers University Cell and DNA Repository (RUCDR) where DNA will be extracted and lymphocytes will be immortalized. DNA, plasma and immortalized lymphocytes will be frozen and stored for future studies. Once the signed documents have been received, medical records and charts will also be retrieved from the appropriate health care provider(s). Detailed clinical information concerning the DILI event will be abstracted from the charts and entered onto case report forms. This information will then be reviewed by the DILIN Causality Committee, and it will make the final determination on whether the patient was a true DILI case.

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。 背景和理由：药物诱导的肝损伤（DILI）是针对药物进行监管行为的最常见原因，包括未能获得营销，从市场上撤离以及限制处方迹象的批准。 DILI也是许多患者人群中发病率和死亡率的重要原因。 为了刺激和促进对DILI的研究，美国国家糖尿病，消化和肾脏疾病（NIDDK）最近建立了药物诱导的肝损伤网络（DILIN）。 该网络要进行的最初项目之一是回顾性建立与药物（ILIAD）相关的严重特质肝损伤的患者，并收集，永生和储存血清，脱氧核糖核酸（DNA），DNA），以及从这些患者中的淋巴细胞来进行这些方案（这些患者的方案）。 该ILIAD协议将作为对严重特质易感性基础的随后机械研究的资源。 具体目的和目标：ILIAD方案的主要目标是创建：（a）由经历了由四种特定药物引起的严重DILI的个体组成的临床数据库，以及有关DILI发作的相关临床数据； （b）创建从这些人获得的生物标本库。 还将收集来自控制对象的相应信息。 这些生物标本将是DNA，血浆和永生的淋巴细胞。 永生的淋巴细胞将提供无限量的基因组DNA进行研究以及活细胞进行表型研究。 ILIAD协议的次要目标是维护ILIAD数据库中的案件注册表，以便将来可以重新连接它们。 预计这将有助于探索DILI机制的其他研究。 Targeted Drugs: The initial drugs to be targeted in the ILIAD protocol are isoniazid (INH), phenytoin, clavulanic acid / amoxicillin (Augmentin and valproic acid. For INH, phenytoin, or clavulanic acid / amoxicillin, severe liver injury is defined as a documented serum total bilirubin > 2.5 mg/dl; for valproic acid, the标准是兼容的症状临床表现，非常严重，可以促使住院和肝功能障碍国际标准化比率（INR）> 1.5或丙氨酸跨激酶（ALT）> 3 x正常（ULN）和/或特征性肝活检的上限）。之所以选择目标药物，是因为与其他药物相比，它们以高率引起严重的DILI，这使得我们的每种药物的目标入学率（n = 50-100）可实现。 此外，这些药物经常用于合理健康的患者，不同时接受其他药物，更可能是肝毒性，从而促进因果关系评估。 基础研究设计：五个稀释林临床中心将以自己的和附属机构识别并与患者联系，这些机构可能因靶向药物之一而遭受肝损伤。 他们还将联系胃肠病学家，肝病学家和其他最有可能治疗DILI病例的医疗保健专业人员。 在后一种情况下，治疗医师将向潜在受试者发送信息包，并要求有兴趣的受试者联系五个临床站点之一。 无论哪种情况，都将简要介绍该研究的目的和程序。 一旦收到该主题的审查这些文件，学习人员将第二次通过电话与潜在主题联系。 这种后续接触将通过电话或亲自在受试者的方便下进行。 将获得知情同意书，如果通过电话发生这种情况，将由该线上的第三方见证。 然后，将使用电话或个人面试格式收集必要的信息。 在结束该电话的第二个联系结束之前，将要求受试者签署同意，HIPAA授权以及发布医疗信息表格并退货将其提供给Dilin临床站点。 将进行鲜血的安排。 血液样本将运送到罗格斯大学细胞和DNA存储库（RUCDR），其中将提取DNA，并将淋巴细胞永生化。 DNA，血浆和永生的淋巴细胞将被冷冻并储存以进行以后的研究。 一旦收到签名文件，也将从适当的医疗保健提供者那里检索病历和图表。 有关DILI事件的详细临床信息将从图表中抽象出来，并输入案例报告表格。 然后，该信息将由稀释林因果关系委员会审查，并将最终确定患者是否是dili案件。