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: 6530131
• 负责人: HAROLD L MOSES
• 金额: $ 13.47万
• 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/6530131
• 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，该病将影响全球 100 万至 25 万人，以及北美超过 350,000 人。疾病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传染源的年龄的影响。范德比尔特大学多发性硬化症实验室最近的工作发现，中枢神经系统感染肺炎衣原体与多发性硬化症之间存在关联。本应用的目的是检查抗生素治疗对多发性硬化症患者脑脊液 (CSF) 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着减少或根除多发性硬化症患者脑脊液中的肺炎衣原体感染，并且治疗后其疾病的临床病程将得到改善。一项为期六个月的随机临床试验将在肺炎衣原体阳性多发性硬化症患者中进行，以检验两种不同抗生素治疗方案与安慰剂的疗效。通过根除培养系统中的肺炎衣原体以及使用定量聚合酶链式反应 (PCR) 测定将 DNA 产物减少 90% 来确定疗效。在找到有效的抗衣原体治疗方案后，第二项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测量。这些患者中有一半将接受抗生素和干扰素-α1b 治疗，另一半将仅接受干扰素-α1b 治疗。这些患者将被随访两年，主要结果指标将是持续进展或残疾的指标。这些研究将确定多发性硬化症患者中枢神经系统肺炎衣原体感染的最佳抗生素治疗，以及抗生素治疗是否有利地改变多发性硬化症的自然史。