A Controlled Trial of CBT for Multiple Sclerosis Inflammation

描述(申请人提供)：多发性硬化症是一种经常致残的自身免疫性疾病，在美国大约有350,000人受到影响。它是美国致残率最高的疾病之一，81%的患者脱离了劳动力大军。二十多年的研究一直表明，压力性生活事件(SLEs)，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存在关系。此外，我们已经证明，非创伤性SLEs增加了随后出现新的Gd+增强(Gd+)磁共振成像(MRI)脑损害的风险，这是MS炎症和血脑屏障(BBB)破坏的早期标志。本研究的目的是确定认知行为疗法对多发性硬化(CBT)的疗效。MS)，这是我们专门为MS开发的一种压力管理程序，用于减少复发-缓解型多发性硬化症(RRMS)患者新的脑损伤的发生。RRMS在其他类型中被选为首选，因为它是MS最常见的形式，而且它比其他类型更有可能与临床恶化和Gd+MRI相关。112名患者将入选为期2年的研究。为了确保患者和治疗部门获得同等的医疗待遇，所有患者都将通过加州大学旧金山分校(UCSF)MS中心接受神经护理。患者将被随机分配到CBT-MS或照常治疗(TAU)。压力管理计划将包括每周26次的小组压力管理培训课程，然后是12个月的强化课程，以鼓励保持行为变化，因为多发性硬化症的恶化是间歇性的，年患病率为0.61-1.68，保持行为变化的时间更长将大大增加检测效果的能力。在停止治疗和加强治疗后，患者将被跟踪6个月。为了鼓励保留，TAU患者将在完成研究后获得26周的CBT-MS。与MS的II期临床试验一致，主要结果将是筛查时、3、6、12、18和24个月获得的Gd+MRI脑损伤。二次神经成像结果将包括T2加权MRI和脑实质分数(BPF)。次要临床结果将包括MS加重率、残疾进展和神经心理损害。生活质量将作为评估临床效用的次要结果进行检查。我们还将通过检查潜在的心理社会、免疫和内分泌调节因素来加强对机制的理解，这些因素可能是系统性红斑狼疮与MS炎症的临床和神经成像标记物之间的关系。

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.