GENOTYPE CORRELATES AND CLINICAL TRIALS IN INHERITED EB

遗传性 EB 的基因型相关性和临床试验

• 批准号: 6171526
• 负责人: JO-DAVID J FINE
• 金额: $ 10.77万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-05-01 至 2004-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6171526
• 关键词: 13 cis retinoate; antioxidants; chemoprevention; clinical research; clinical trials; cytokine; dietary supplements; disease /disorder prevention /control; epidermolysis bullosa; family genetics; gastrointestinal surgery; genetic disorder; genotype; human subject; human therapy evaluation; nutrition related tag; outcomes research; patient care management; phenotype; retinoids; skin disorder chemotherapy; squamous cell carcinoma; topical drug application; vitamin therapy

Inherited epidermolysis bullosa (EB) encompasses those diseases characterized by mechanically fragile skin and the tendency for blister formation. As of May 1998, four major types, at least 23 phenotypically distinctive subtypes, and at least 200 different genotypes have been described. Now that over 3,000 clinically well characterized patients with EB have been assembled via the National EB Registry, we propose to use the Registry, and the mechanism of a K24 Award, to attempt to address several clinically relevant and timely issues, to include (1) phenotype - genotype correlations across both major and minor types and subtypes of inherited EB, and the identification of those genotypes which have specific prognostic or therapeutic significance., (2) initiation of a prospective interventional clinical trial to assess the possible beneficial role of isotretinoin or another systemic retinoid as a chemopreventive agent against the development of additional squamous cell carcinomas in those patients with RDEB-HS who have developed at least one such tumor; (3) initiation of one or more other clinical trials to determine the benefit, if any, in the performance of selected medical or surgical interventions in groups of patients having more severe forms of EB, to include (a) early elective gastrostomy placement, (b) hand splinting, (c) use of one or more topical cytokine preparations and/or newer wound, healing dressings, (d) the use of topical or systemic antioxidant agents, and (e) aggressive nutritional supplementation; and (4) characterization of baseline metabolic and nutritional parameters in patients with severe generalized forms of inherited EB. It is hoped that the results of these several proposed clinical studies will provide new insights into the management of patients with EB, as well as provide an excellent means whereby young investigators interested in patient-oriented research can be mentored and trained.

遗传性大疱性表皮松解症（EB）包括那些以皮肤机械脆弱和水疱形成倾向为特征的疾病。截至1998年5月，已经描述了四种主要类型，至少23种表型不同的亚型和至少200种不同的基因型。现在，通过国家EB登记处已经收集了3000多名临床特征明确的EB患者，我们建议使用该登记处和K24奖的机制，试图解决几个临床相关和及时的问题，包括：(1)遗传性EB的主要和次要类型和亚型之间的表型-基因型相关性，以及识别那些具有特定预后或治疗意义的基因型。(2)启动一项前瞻性干预性临床试验，评估异维甲酸或另一种系统性类维甲酸作为化学预防剂，在已经发生至少一种鳞状细胞癌的rdebb - hs患者中预防鳞状细胞癌发展的可能有益作用；(3)启动一项或多项其他临床试验，以确定对患有更严重形式EB的患者群体进行选定的医疗或手术干预的益处（如果有的话），包括(a)早期选择性胃造口放置，(b)手部夹板，(c)使用一种或多种局部细胞因子制剂和/或较新的伤口愈合敷料，(d)使用局部或全身抗氧化剂，以及(e)积极的营养补充；(4)严重全身性遗传性EB患者的基线代谢和营养参数特征。希望这几项拟议的临床研究的结果将为EB患者的管理提供新的见解，并为对患者导向研究感兴趣的年轻研究者提供良好的指导和培训。