Controlled Trial of DBS for OCD

描述（由申请人提供）：难治性强迫症（OCD）仍然是一个重大的公共卫生问题。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，从而降低生活质量。我们的三个合作试点研究表明，深部脑刺激（DBS）内囊腹侧前肢和邻近的腹侧纹状体（VC/VS）对其他抵抗性强迫症有效。该设备（由美敦力公司制造）是fda唯一批准用于脑刺激的设备，在帕金森病、震颤和肌张力障碍方面具有已证实的有效性和安全性。在七年的强迫症试点工作中，大脑靶点已经被细化，有效的DBS参数已经确定。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强迫症DBS治疗方面经验最丰富的机构，包括NIMH试点试验机构。45名患者将被纳入随机、平行、对照设计。我们将使用完善的程序来确定患者是否对药物和行为疗法有抗药性。注册时需要对诊断、治疗史和同意过程进行独立评估。在最初的四年里，患者将以每年11-12人的速度入组。我们将在三个月的时间里比较隐蔽的刺激和假刺激，以获得主要的疗效和安全性数据。DBS反应的标准将是绝对和严格的：症状（耶鲁-布朗强迫症量表得分降低35%）和整体功能的改善。在3个月的对照期后，开放DBS将继续进行1-4年，以获得长期的有效性和安全性数据。基线的正电子发射断层扫描将用于获得脑代谢反应的预测因子。在至少三个月的刺激后进行重复扫描，将验证与强迫症有关的皮质基底网络的活动在DBS后会发生变化的假设。如果成功的话，可逆的DBS将给那些几乎没有治疗选择的严重患者带来希望。成像数据将为大脑网络预测和调解对顽固性强迫症的DBS反应提供独特的见解。

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.