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）：大量的临床前和临床工作证明了5-羟色胺系统在酒精中毒中的参与。 最近对两项成功的5-羟色胺药物临床试验的出版物对该领域具有巨大的希望。 一项研究表明，SSRI舍曲林在晚期（A型）酒精中毒中具有显着影响，而另一项则表现出5-HT3抗抗酸剂的ondangogist Ondansetron在早期发病的酒精中毒中的功效。 在酒精中毒中没有其他预测治疗反应的预测指标。 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，可以识别可能与酒精中毒相关或与之相关的特定大脑区域。神经内分泌，生理，主观和最近[18 F] Fluoro-脱氧 - 葡萄糖（FDG）对广泛的血清素血清素激动剂M-CPP的PET扫描反应均已用于检查酒精中毒中的5-羟色胺系统，并以前已用于预测对其他精神疾病中血清素药物的临床反应。 FDG PET扫描最近还开始为我们提供对抑郁症和其他疾病中血清素能药物的区域药物治疗反应的了解，但在酒精中毒中尚未这样做。 我们提出了一项在酒精中毒中血清素能药物的临床试验，并在研究结束前添加了预测性5-羟色胺神经成像和神经内分泌探针，并在研究结束时进行了后续成像扫描。 我们将服用100名最近戒酒的酗酒者，开出200mg的舍曲林以及每周的认知行为心理治疗，并在12周期间跟随它们。 我们将在试验前完成撤回后进行M-CPP FDG PET扫描和安慰剂FDG PET扫描，并在完成试验后进行FDG PET扫描。 我们的目的是：首先，研究通过一组酗酒者在安慰剂FDG-PET扫描中，由五羟色胺探针M-CPP诱导的FDG-PET扫描所测量的区域脑代谢的变化，并将其与一组健康的对照组进行比较；其次，将M-CPP诱导的脑代谢变化与静脉反应的临床反应相关联，在12周期间，在酗酒者的舍曲林治疗试验中；最后，要评估舍曲林对安慰剂FDG-PET扫描区域代谢的变化的影响，并将脑代谢的变化与治疗结果相关联。 我们假设对舍曲林的响应将有一组临床反应者和非反应者，并且在试验之前，血清素能反应，脑区域代谢，荷尔蒙，生理或主观的程度对M-CPP挑战的程度将预测试验中对塞特拉林的治疗反应。 我们还将假设在治疗敏感舍曲林组中FDG-PET扫描的归一化。 这项研究应有助于确定一组治疗疗法者对舍曲林的反应者，检查是否可以使用神经成像和神经内分泌技术来预测该治疗反应，并确定在基线和治疗时与哪些大脑区域有关。