Controlled Trial of DBS for OCD

描述(申请人提供)：难以治疗的强迫症(OCD)仍然是一个严重的公共卫生问题。尽管进行了积极的常规治疗，但痛苦和功能障碍可能会继续下去，降低生活质量。我们的三项合作初步研究表明，内囊腹侧前肢和邻近腹侧纹状体(VC/VS)的脑深部刺激(DBS)对其他抵抗的强迫症是有效的。这些设备(由美敦力公司制造)是FDA唯一批准用于脑刺激的药物，已证明对帕金森病、震颤和肌张力障碍有疗效和安全性。在七年的强迫症试点工作中，大脑目标得到了细化，并确定了有效的DBS参数。我们建议进行更明确的对照试验。这项为期五年的合作研究涉及美国三个在DBS治疗强迫症方面经验最丰富的网站，其中包括NIMH试点网站。45名患者将参加随机、平行、对照设计。我们将使用成熟的程序来确定患者是否对药物和行为疗法有抵抗力。注册需要对诊断、治疗历史和同意过程进行独立评估。患者将在头四年内登记，每年11-12人。我们将在三个月内比较掩蔽的积极刺激和假刺激，以获得初步的疗效和安全性数据。星展银行的反应标准将是明确和严格的：两种症状的改善(耶鲁-布朗强迫量表得分下降35%)和全球功能改善。在为期三个月的受控阶段后，星展银行开放将持续1-4年，以获得长期有效和安全的数据。基线正电子发射断层扫描将被用来获得大脑代谢反应的预测指标。在至少三个月的刺激后进行重复扫描，将检验与强迫症有关的皮质-基础网络活动在DBS后将发生变化的假设。如果成功，可逆转的DBS将为几乎没有治疗选择的严重受影响的人带来希望。成像数据将为预测和调节DBS治疗难治性强迫症的反应的大脑网络提供独特的见解。

DESCRIPTION (provided by applicant): Treatment-resistant obsessive-compulsive disorder (OCD) remains a significant public health problem. Despite aggressive conventional treatment, suffering and functional impairment may continue, degrading quality of life. Our three collaborative pilot studies suggest that deep brain stimulation (DBS) of the ventral anterior limb of internal capsule and adjacent ventral striatum (VC/VS) is effective in otherwise resistant OCD. The devices (made by Medtronic, Inc.) are uniquely FDA-approved for brain stimulation, with proven efficacy and safety in Parkinson disease, tremor, and dystonia. In seven years of pilot OCD work, the brain target has been refined and effective DBS parameters identified. We propose a more definitive controlled trial. This collaborative, five-year study involves the three U.S. sites most experienced in DBS for OCD, including the NIMH pilot trial site. Forty-five patients will enroll in a randomized, parallel, controlled design. We will use well-established procedures to determine if patients are resistant to medication and behavior therapies. Independent assessments of diagnosis, treatment history, and the consent process will be required for enrollment. Patients will enroll, 11-12/year, over the first four years. We will compare masked active to sham stimulation over three months to obtain primary efficacy and safety data. The criterion for DBS response will be categorical and strict: improvement in both symptoms (a 35% Yale-Brown Obsessive- Compulsive Scale score reduction) and in global functioning. After the three-month controlled phase, open DBS will continue for 1-4 years to obtain long-term effectiveness and safety data. Positron emission tomography at baseline will be used to obtain brain metabolic predictors of response. A repeat scan after at least three months of stimulation will test the hypothesis that activity in corticobasal networks implicated in OCD will change after DBS. If successful, reversible DBS will offer hope to severely affected people with few treatment options. The imaging data will provide unique insight into brain networks predicting and mediating the response to DBS for intractable OCD.