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。尽管积极的常规治疗，痛苦和功能障碍可能会继续，降低生活质量。我们的三个合作试点研究表明，脑深部电刺激（DBS）的腹侧前肢的内囊和相邻的腹侧纹状体（VC/VS）是有效的，否则抵抗强迫症。器械（由Medtronic，Inc.制造）是唯一获得FDA批准的脑刺激，在帕金森病、震颤和肌张力障碍中具有经证实的疗效和安全性。在七年的试验性OCD工作中，大脑目标已经得到了改进，有效的DBS参数得到了确定。我们提出了一个更明确的对照试验。这项为期五年的合作研究涉及三个在DBS治疗强迫症方面经验最丰富的美国研究中心，包括NIMH试点试验中心。45例患者将入组随机、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抵抗力。入组时需要对诊断、治疗史和知情同意过程进行独立评估。患者将在前四年入组，每年11-12例。我们将在三个月内比较设盲的活性刺激与假刺激，以获得主要疗效和安全性数据。DBS反应的标准将是明确和严格的：两种症状（耶鲁-布朗强迫量表评分降低35%）和整体功能改善。在3个月的对照阶段后，开放DBS将继续1-4年，以获得长期有效性和安全性数据。基线时的正电子发射断层扫描将用于获得反应的脑代谢预测因子。刺激至少三个月后的重复扫描将检验与强迫症有关的皮质基底神经网络的活动在DBS后会发生变化的假设。如果成功，可逆DBS将为几乎没有治疗选择的严重受影响的人提供希望。成像数据将为预测和介导DBS治疗顽固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.