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: 6617867
• 负责人: HAROLD L MOSES
• 金额: $ 13.36万
• 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/6617867
• 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125万人受到影响，北美洲有35万多人受到影响。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传染因子的年龄的影响。范德比尔特大学MS实验室最近的研究发现肺炎衣原体CNS感染与MS之间存在关联。MS患者脑脊液（CSF）中的肺炎感染。我们假设适当的抗生素治疗将显著减少或根除C。在MS患者的CSF中的肺炎感染，并且其疾病的临床病程将在治疗后改善。一项随机临床试验将在6个月的时间内在C.肺炎阳性MS患者。疗效将通过根除C.在培养系统中检测肺炎克雷伯氏菌，并使用定量聚合酶链反应（PCR）测定法检测DNA产物减少90%。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在继发性进展型多发性硬化（SPMS）患者队列中检查临床结局指标。这些患者中有一半将接受抗生素和干扰素治疗。1b和另一半干扰素？单独1b。这些患者将被随访两年，主要结局指标将是持续进展或残疾的指标。这些研究将确定CNS C的最佳抗生素治疗。肺炎感染的MS患者，如果抗生素治疗有利改变MS的自然史。