A Controlled Trial of CBT for MS Inflammation

描述（由申请人提供）：MS是一种经常致残的自身免疫性疾病，在美国影响约350，000人。它是美国最具致残性的疾病之一，81%的患者无法工作。二十多年的研究一直表明，压力性生活事件（SLE），特别是非创伤性家庭和工作压力源，与随后的临床恶化之间的关系。此外，我们已经表明，非创伤性SLE增加了随后出现新的钆增强（Gd+）磁共振成像（MRI）脑损伤的风险，这是MS炎症和血脑屏障（BBB）破坏的早期标志物。本研究的目的是确定认知行为疗法（CBT）治疗MS的疗效。MS），我们专门为MS开发的压力管理计划，在减少复发缓解型多发性硬化症（RRMS）患者新发脑病变的发生方面。选择RRMS而不是其他类型，因为它是MS的最常见形式，并且比其他类型更可能与临床加重和Gd+ MRI相关。112例患者将入组2年。为了确保患者和治疗组之间的等效医疗，所有患者将通过加州大学旧金山弗朗西斯科（UCSF）MS中心接受神经系统护理。患者将被随机分配至CBT-MS或常规治疗（TAU）。压力管理计划将包括26次每周一次的团体压力管理培训课程，随后是12次每月一次的加强课程，以鼓励维持行为变化。由于MS恶化是偶发性的，年患病率为0.61 - 1.68，因此更长时间维持行为变化将大大增加检测效果的能力。患者将在停止治疗和加强治疗后随访6个月。为了鼓励保留，TAU患者将在完成研究后接受26周的CBT-MS治疗。与MS II期临床试验一致，主要结局将是筛选时以及第3、6、12、18和24个月时获得的Gd+ MRI脑病变。次要神经影像学结局将包括T2加权MRI和脑实质分数（BPF）。次要临床结局将包括MS加重率、残疾进展和神经心理学损害。生活质量将作为次要结局进行检查，以评价临床效用。我们还将通过检查SLE与MS炎症的临床和神经影像学标志物之间关系的潜在心理社会、免疫和内分泌介质来增强对机制的理解。

DESCRIPTION (provided by applicant): MS is a frequently disabling autoimmune disease affecting approximately 350,000 people in the United States. It is among the most disabling diseases in the United States, with 81% of all patients out of the workforce. More that two decades of research has consistently shown a relationship between stressful life events (SLEs), in particular non-traumatic family and work stressors, and subsequent clinical exacerbation. Furthermore, we have shown that non-traumatic SLEs increase the risk of the subsequent appearance of new gadolinium enhancing (Gd+) magnetic resonance imaging (MRI) brain lesions, an early marker of MS inflammation and blood-brain barrier (BBB' breakdown. The purpose of this study is to determine the efficacy of cognitive behavioral therapy for MS (CBT. MS), a stress management program we have developed specifically for MS, in reducing the occurrence of new brain lesions in people with relapsing-remitting multiple sclerosis (RRMS). RRMS was selected over other types, because it is the most common form of MS and it is more likely than other types to be associated with clinical exacerbation and Gd+ MRI. One hundred and twelve patients will be enrolled for 2 years. To ensure equivalent medical treatment across patients and treatment arms, all patients will receive neurological care through the University of California, San Francisco (UCSF) MS Center. Patients will be randomly assigned to either CBT-MS or treatment as usual (TAU). The stress management program will consist of 26 weekly group stress management training sessions followed by 12 monthly booster sessions to encourage maintenance of behavioral changes, Because MS exacerbation is episodic, with annual prevalence rates of .61 - 1.68, longer maintenance of behavioral changes will greatly increase the power to detect effects. Patients will be followed for 6 months following cessation of treatment and booster sessions. To encourage retention, TAU patients will be offered 26 weeks of CBT-MS after completing the study. Consistent with Phase II clinical trials in MS, the primary outcome will be Gd+ MRI brain lesions acquired at screening, and months 3, 6, 12, 18, and 24. Secondary neuroimaging outcomes will include T2-weighted MRI and brain parenchymal fraction (BPF). Secondary clinical outcomes will include MS exacerbation rate, progression of disability, and neuropsychological impairment. Quality of life will be examined as a secondary outcome to evaluate clinical utility. We also wilt enhance our understanding of mechanisms by examining potential psychosocial, immune, and endocrine mediators of the relationship betweenSLEs and clinical and neuroimaging markers of MS inflammation.