Eval of Efficacy/Mechs of Anti-inflammatory Intervention

抗炎干预的功效/机制评价

• 批准号: 7137963
• 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/7137963
• 关键词: antiinflammatory agents; biological signal transduction; blood chemistry; bone marrow; chemotherapy; chimeric proteins; clinical trials; drug screening /evaluation; human subject; human therapy evaluation; inflammation; mouthwash; oral administration; oral facial pain; patient oriented research; polymerase chain reaction; stem cell transplantation; stomatitis; tumor necrosis factor alpha

Stomatitis is defined as inflammation of the mucous membranes of the oral cavity and oropharynx characterized by tissue erythema, edema, and atrophy, often progressing to ulceration. Stomatitis is a biologically complex, multifactorial, treatment-related oral condition experienced by many oncology patients, which often leads to a cascade of negative sequelae including oropharyngeal pain, critical treatment alterations or cessation, and decreased quality of life. The optimal treatment strategies for stomatitis have not been established. There is a critical need to examine the pathogenesis of and to evaluate interventions for stomatitis and related acute oropharyngeal pain in the randomized controlled clinical trial setting using valid and reliable stomatitis assessment tools to both advance the science of cancer treatment-related oral toxicities and improve patient care. Therefore, the purpose of this randomized controlled clinical trial is to elucidate the role of inflammation in stomatitis by testing the effects of a novel tumor necrosis factor (TNF) fusion protein etanercept, (Enbrel?, Immunex Corporation, Seattle, WA) on the incidence and severity of stomatitis. The actions of this fusion protein, which binds specifically to TNF preventing its interaction with cellular receptors and altering the inflammatory cascade, may provide insight into the role of inflammation in stomatitis. An etanercept effect is defined as a prevention or amelioration of stomatitis and acute oropharyngeal pain and/or changes in levels of tissue mediators. If stomatitis is primarily a consequence of a mucosal inflammatory response, then we hypothesize that this oral condition will be responsive to binding of TNF-alpha. Elaboration of the role of inflammatory cell signalling associated with stomatitis and the effect of TNF-alpha may elucidate the mechanisms related to the pathogenesis of stomatitis and to other mucosal conditions. Patients who are scheduled to receive stomatogenic chemotherapy with autologous peripheral blood stem cell transplanation, ages 16 years or older, will be invited to participate in this study during a regularly scheduled pre-treatment visit in the National Institute of Dental and Craniofacial Research Dental Clinic, or through established recruitment strategies at a National Cancer Institute sponsored Community Clinical Oncology Program located at the Cancer Centers of the Carolinas, Greenville, SC. Written informed consent will be obtained from all participants. Patients will be randomized to receive either etanercept mouthwash or placebo, which will both be administered by protocol schedule. Stomatitis and oropharyngeal pain will be measured at baseline and at specified post-chemotherapy time points corresponding with the predicted stomatitis onset, peak, and healing time course. TNF-alpha levels in buccal mucosa, analyzed by real time polymerase chain reaction techniques, and blood levels of pro-inflammatory cytokines, growth factors, and inflammatory mediators will also be measured at baseline and at specified post-chemotherapy time points corresponding with the predicted stomatitis onset, peak, and healing time course. This study will begin to accrue subjects following the approval of the data and safety monitoring plan by the Data and Safety Monitoring Board, which convened in Augsut, 2005. The study transferred from the National Institute of Dental and Craniofacial Research to the National Institute of Nursing Research in 2004.

口腔炎的定义是口腔和口咽粘膜的炎症，以组织红斑、水肿和萎缩为特征，通常进展为溃疡。口腔炎是一种生物学上复杂的、多因素的、与治疗相关的口腔疾病，许多肿瘤患者都会经历这种情况，它通常会导致一连串的负面后遗症，包括口咽部疼痛、严重的治疗改变或停止治疗，以及生活质量下降。口腔炎的最佳治疗策略尚未确定。在随机对照临床试验中，迫切需要使用有效和可靠的口腔炎评估工具来检查口腔炎和相关急性口咽痛的发病机制并评估干预措施，以促进癌症治疗相关口腔毒性的科学研究，并改善患者护理。因此，这项随机对照临床试验的目的是通过测试一种新型的肿瘤坏死因子(TNF)融合蛋白etanercept(Enbrel？，免疫公司，西雅图，华盛顿州)对口腔炎的发病率和严重程度的影响来阐明炎症在口腔炎中的作用。这种融合蛋白特异性地与肿瘤坏死因子结合，阻止其与细胞受体的相互作用，并改变炎症级联反应，可能有助于深入了解炎症在口腔炎中的作用。依那西普效应被定义为预防或改善口腔炎和急性口咽疼痛和/或组织介质水平的变化。如果口腔炎主要是粘膜炎症反应的结果，那么我们假设这种口腔疾病将对肿瘤坏死因子-α的结合产生反应。阐明与口腔炎相关的炎症细胞信号转导的作用和肿瘤坏死因子-α的作用，可能会阐明口腔炎的发病机制和其他粘膜状况。 计划接受口腔化疗和自体外周血干细胞移植的患者，年龄在16岁或以上，将被邀请参加这项研究，他们将在国家牙科和颅面研究牙科诊所定期安排的治疗前访问期间参与这项研究，或者通过位于南卡罗来纳州格林维尔癌症中心的国家癌症研究所赞助的社区临床肿瘤学计划的既定招募战略参与。将获得所有参与者的书面知情同意。患者将随机接受依那西普漱口水或安慰剂，这两种药物都将按协议时间表给药。口腔炎和口咽疼痛将在基线和特定的化疗后时间点进行测量，这些时间点与预测的口腔炎发病、高峰和愈合时间进程相对应。通过实时聚合酶链式反应技术分析口腔黏膜中的肿瘤坏死因子-α水平，并在基线和特定的化疗后时间点测量促炎症细胞因子、生长因子和炎症介质的血液水平，这些时间点与预测的口腔炎发病、高峰和愈合时间进程相对应。 在2005年8月召开的数据和安全监测委员会核准数据和安全监测计划之后，这项研究将开始引起关注。这项研究于2004年从国家牙科和颅面研究所转移到国家护理研究所。