M-CPP PET Scanning of Alcoholism:Effects of Sertraline

酒精中毒的 M-CPP PET 扫描：舍曲林的影响

• 批准号: 6916499
• 负责人: MONTE Stuart BUCHSBAUM
• 金额: $ 42.38万
• 依托单位: ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-09-26 至 2007-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6916499
• 关键词: alcoholism /alcohol abuse; behavior therapy; bioimaging /biomedical imaging; brain metabolism; cerebral cortex; chemotherapy; clinical research; clinical trials; combination therapy; human subject; human therapy evaluation; neuroimaging; ondansetron; outcomes research; patient oriented research; positron emission tomography; serotonin; sertraline

DESCRIPTION (provided by applicant): A significant body of preclinical and clinical work demonstrates the involvement of the serotonin system in alcoholism. Recent publication of two successful clinical trials of serotonin medications holds significant promise for the field. One study demonstrated a significant effect of the SSRI sertraline in late-onset (type A) alcoholics, while the other demonstrated efficacy of the 5-HT3-antagonist ondansetron in early-onset alcoholics. No other predictors of treatment response have been developed in alcoholism. Neuroimaging, particularly positron emission tomography (PET) scanning, offers a powerful tool to identify specific brain regions that may underlie or be associated with alcoholism. Neuroendocrine, physiological, subjective and recently [18 F] fluoro-deoxy-glucose (FDG) PET scanning responses to the broad spectrum serotonin agonist m-CPP have all been used to examine the serotonin system in alcoholism, and have previously been used to predict the clinical response to serotonin medications in other psychiatric disorders. FDG PET scanning has also recently begun to offer us an understanding of the regional pharmacotherapeutic treatment response to a serotonergic medication in depression, and in other disorders, but has yet to do so in alcoholism. We propose a clinical trial of a serotonergic medication in alcoholism, with the addition of a predictive serotonin neuroimaging and neuroendocrine probe before the study, and a follow up imaging scan at the end of the study. We will take 100 recently abstinent alcoholics, prescribe 200mg of sertraline together with weekly cognitive behavioral psychotherapy, and follow them for a 12-week period. We will perform an m-CPP FDG PET scan and a placebo FDG PET scan on completion of withdrawal prior to the trial, and an FDG PET scan on completion of the trial. Our aims are: firstly, to study changes in regional cerebral metabolism measured by FDG-PET scan induced by serotonin probe m-CPP relative to placebo FDG-PET scans in a group of alcoholics, and compare them with a group of healthy controls; secondly, to correlate the m-CPP induced changes in brain metabolism with the clinical response in a treatment trial of sertraline in the group of alcoholics over a 12-week period; and lastly, to assess the effect of sertraline on changes in placebo FDG- PET scans' regional metabolism, and to correlate changes in brain metabolism with treatment outcome. We hypothesize there will be group of clinical responders and non-responders in response to sertraline, and that the degree of serotonergic response, cerebral regional metabolic, hormonal, physiological or subjective, to the m-CPP challenge prior to the trial will predict the treatment response to sertraline in the trial. We would also hypothesize normalization of the FDG-PET scans in the treatment responsive sertraline group. This study should help identify a group of treatment responders to sertraline, examine whether that treatment response can be predicted using neuroimaging and neuroendocrine techniques, and identify what brain regions are implicated at baseline and in response to treatment.

描述（由申请人提供）：大量临床前和临床工作证明了血清素系统与酗酒有关。 最近发表的两项成功的血清素药物临床试验为该领域带来了巨大的希望。 一项研究证明 SSRI 舍曲林对晚发性（A 型）酗酒者有显着疗效，而另一项研究则证明 5-HT3 拮抗剂昂丹司琼对早发性酗酒者有效。 尚未开发出其他酒精中毒治疗反应的预测因子。 神经影像学，特别是正电子发射断层扫描 (PET) 扫描，提供了一种强大的工具来识别可能与酗酒相关的特定大脑区域。神经内分泌、生理、主观以及最近对广谱血清素激动剂 m-CPP 的 [18 F] 氟脱氧葡萄糖 (FDG) PET 扫描反应均已用于检查酒精中毒中的血清素系统，并且之前已用于预测其他精神疾病对血清素药物的临床反应。 FDG PET 扫描最近也开始让我们了解抑郁症和其他疾病对血清素药物的局部药物治疗反应，但在酗酒方面尚未做到这一点。 我们建议对酒精中毒的血清素药物进行临床试验，在研究前添加预测性血清素神经影像和神经内分泌探针，并在研究结束时进行后续影像扫描。 我们将选取 100 名最近戒酒的人，给他们开 200 毫克舍曲林，同时每周进行认知行为心理治疗，并跟踪他们 12 周。 我们将在试验前完成退出时进行 m-CPP FDG PET 扫描和安慰剂 FDG PET 扫描，并在试验完成后进行 FDG PET 扫描。 我们的目的是：首先，研究一组酗酒者中由血清素探针 m-CPP 诱导的 FDG-PET 扫描相对于安慰剂 FDG-PET 扫描测量的局部脑代谢的变化，并将其与一组健康对照进行比较；其次，将 m-CPP 诱导的脑代谢变化与在酗酒者群体中进行的舍曲林治疗试验 12 周内的临床反应相关联；最后，评估舍曲林对安慰剂 FDG-PET 扫描局部代谢变化的影响，并将脑代谢变化与治疗结果相关联。 我们假设存在一组对舍曲林有反应的临床反应者和无反应者，并且试验前对 m-CPP 挑战的血清素能反应程度、脑区域代谢、激素、生理或主观反应将预测治疗效果试验中对舍曲林的反应。 我们还假设治疗反应性舍曲林组的 FDG-PET 扫描正常化。 这项研究应有助于确定一组对舍曲林治疗有反应的人，检查是否可以使用神经影像学和神经内分泌技术来预测治疗反应，并确定哪些大脑区域涉及基线和对治疗的反应。