MENTORED PATIENT-ORIENTED RESEARCH CAREER DEVELOPMENT AW

指导以患者为导向的研究职业发展 AW

• 批准号: 6229536
• 负责人: HAROLD L MOSES
• 金额: $ 13.63万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2000
• 资助国家: 美国
• 起止时间: 2000-09-30 至 2005-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6229536
• 关键词: Chlamydiaceae; antibacterial antibody; antibiotics; bacteria infection mechanism; bacterial pneumonia; central nervous system; cerebrospinal fluid; clinical research; clinical trials; combination chemotherapy; drug screening /evaluation; enzyme linked immunosorbent assay; human subject; human therapy evaluation; interferons; longitudinal human study; multiple sclerosis; nervous system disorder chemotherapy; nervous system infection; outcomes research; pathologic process; placebos; polymerase chain reaction; tissue /cell culture

It is estimated to affect between one million and one and a quarter million people worldwide and over 350,000 persons in North America. Disease susceptibility appears to be influenced by genetic determinants, location of residence through adolescence, and possibly age of exposure to certain infectious agents. Recent work in the MS laboratory at Vanderbilt University has found an association between CNS infection with Chlamydia pneumoniae and MS. The objectives of this application are to examine the role antibiotic therapy has on C. pneumoniae infection in the cerebrospinal fluid (CSF) of MS patients. We hypothesize that appropriate antibiotic therapy will markedly reduce or eradicate C. pneumoniae infection in the CSF of MS patients and that the clinical course of their disease will improve following treatment. A randomized clinical trial to examine the efficacy of two different antibiotic regimens versus placebo will be done over a six-month period of time in C. pneumoniae positive MS patients. Efficacy will be determined by eradication of C. pneumoniae in a culture system and a 90% reduction of DNA products using a quantitative polymerase chain reaction (PCR) assay. After an effective anti-chlamydial regimen has been found, a second randomized clinical trial will examine clinical outcome measures in a cohort of secondary progressive multiple sclerosis (SPMS) patients. Half of these patients will receive antibiotics and interferon-?1b and the other half interferon-?1b alone. These patients will be followed for two years and the primary outcome measure will be measures of sustained progression or disability. These studies will determine both the optimal antibiotic treatment of CNS C. pneumoniae infection in MS patients and if antibiotic therapy favorable alters the natural history of MS.

据估计，全世界有100万至25万人受到影响，北美有超过35万人受到影响。疾病的易感性似乎受到遗传决定因素、青春期居住地点以及可能接触某些感染性物质的年龄的影响。范德比尔特大学多发性硬化症实验室最近的工作发现，中枢神经系统肺炎衣原体感染与多发性硬化症之间存在关联。这项应用的目的是研究抗生素治疗对多发性硬化症患者脑脊液中肺炎衣原体感染的作用。我们假设，适当的抗生素治疗将显著减少或消除MS患者脑脊液中肺炎衣原体的感染，并且他们的临床病程将在治疗后得到改善。一项随机临床试验将对肺炎衣原体阳性多发性硬化症患者进行为期六个月的临床试验，以检验两种不同抗生素方案与安慰剂的疗效。疗效将通过在培养系统中根除肺炎衣原体和使用定量聚合酶链式反应(PCR)将DNA产物减少90%来确定。在找到有效的抗衣原体方案后，第二个随机临床试验将检查继发性进行性多发性硬化症(SPMS)患者队列的临床结果。其中一半的患者将接受抗生素和干扰素-1B，另一半仅接受干扰素-1B。这些患者将被跟踪两年，主要结果将是持续进展或残疾的衡量标准。这些研究将确定MS患者肺炎链球菌感染的最佳抗生素治疗，以及抗生素治疗是否有利于改变MS的自然病史。