Evaluation of Efficacy and Mechs of Topical Thalidomide

外用沙利度胺的疗效及机制评价

• 批准号: 7137961
• 负责人: jane fall-dickson
• 金额: --
• 依托单位: NATIONAL INSTITUTE OF NURSING RESEARCH
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/7137961
• 关键词: chemotherapy; chronic disease /disorder; clinical trials; dosage forms; drug classification; drug screening /evaluation; graft versus host disease; human subject; human therapy evaluation; inflammation; oral facial pain; pathologic process; patient oriented research; stomatitis; thalidomide; tumor necrosis factor alpha

The purpose of this randomized controlled clinical trial is to elucidate the role of inflammation in chronic graft-versus-host-disease (cGVHD)-related stomatitis by testing the effects of a novel topical tumor necrosis factor (TNF)-alpha modulator, thalidomide, versus placebo for this oral condition. The specific aims of this study are the following: 1) to assess the clinical efficacy of topical thalidomide for treatment of cGVHD-related stomatitis; 2) to assess the safety and tolerability of topical thalidomide for the treatment of cGVHD-related stomatitis; and 3) to examine the role of inflammation in cGVHD related stomatitis using topically applied thalidomide as a pharmacologic tool. Our overall hypothesis is that the cytokine TNF-alpha plays a major role in the pathogenesis of cGVHD-related stomatitis via the local inflammatory response, which is modified by the topical application of the putative TNF-alpha modulator, thalidomide. The study is planned to test the effectiveness of topical thalidomide versus placebo in a paste formulation (N = 66), and also in a mouthwash formulation (N = 66). Inclusion criteria include patients between the ages of 18 and 80 who have a diagnosis of oral cGVHD as confirmed by surgical biopsy results. The study will begin to accrue subjects following the approval of the protocol data and safety monitoring plan by the Data and Safety Monitoring Board, which convened in August, 2005. In addition to the patient population provided by Richard Childs, MD, Associate Investigator, National Heart, Lung, and Blood Institute, cGVHD patients may be referred through the weekly National Cancer Institute sponsored cGVHD Clinic at the Clinical Center, National Institutes of Health (NIH), as well as through the National Cancer Institute-sponsored cGVHD natural history protocol "Prospective Assessment of Clinical and Biological Factors Determining Outcomes in Patients with cGVHD" (04-C-0281). Topical thalidomide is prepared by the Pharmaceutical Development Service, Clinical Center, NIH. The IRB was informed on September 20, 2004 that the protocol was transferred from the National Insitute of Dental and Craniofacial Research to the National Institute of Nursing Research.

这项随机对照临床试验的目的是通过测试一种新型局部肿瘤坏死因子（TNF）-α调节剂沙利度胺与安慰剂对慢性移植物抗宿主病（cGVHD）相关口腔炎的影响，阐明炎症在这种口腔疾病中的作用。本研究的具体目的如下：1）评估局部沙利度胺治疗cGVHD相关口腔炎的临床疗效; 2）评估局部沙利度胺治疗cGVHD相关口腔炎的安全性和耐受性;和3）使用局部应用的沙利度胺作为药理学工具检查炎症在cGVHD相关口腔炎中的作用。我们的总体假设是，细胞因子TNF-α通过局部炎症反应在cGVHD相关性口腔炎的发病机制中起主要作用，局部应用假定的TNF-α调节剂沙利度胺可以改变局部炎症反应。该研究计划测试局部沙利度胺与安慰剂在糊剂制剂（N = 66）和漱口剂制剂（N = 66）中的有效性。入选标准包括年龄在18岁至80岁之间的患者，其具有经手术活检结果证实的口腔cGVHD诊断。 在2005年8月召开的数据和安全性监查委员会批准方案数据和安全性监查计划后，研究将开始招募受试者。除了由Richard查尔兹，MD，国家心脏、肺和血液研究所的副研究员提供的患者群体之外，cGVHD患者可以通过每周国家癌症研究所赞助的cGVHD诊所在临床中心，国立卫生研究院（NIH），以及通过国家癌症研究所赞助的cGVHD自然史方案“决定cGVHD患者结局的临床和生物学因素的前瞻性评估”（04-C-0281）。局部沙利度胺由NIH临床中心药物开发服务处制备。 IRB于2004年9月20日获悉，方案已从国立牙科和颅面研究所转移至国立护理研究所。