Bell's Palsy-Randomized Clinical Trial

描述（由申请人提供）：贝尔麻痹是一种突如其来的单侧面神经麻痹，无明确原因，累及面神经的所有分支，每年约有23/100,000人受到影响。1型单纯疱疹病毒是推测的病因。直觉导致使用抗炎药，主要是口服强的松，与口服抗病毒药物联合使用，如阿昔洛韦或其前药valacyclovir。先前研究抗炎和抗病毒干预对贝尔麻痹的影响的努力受到研究设计不佳、纳入标准不同和终点顺序定义不同的阻碍。这些方法上的问题阻碍了对这些干预措施有效性的科学评估，并导致对结果的估计大相径庭。因此，最被广泛引用的统计数据——71%未经治疗的受试者恢复正常——似乎是错误的和不可支持的。有证据表明，只有24%的人完全恢复正常，其余的人受到永久性影响，16%的人有明显的毁容。此外，有一些证据表明，这些药物可能会造成伤害或阻碍康复。我们建议在300名受试者中进行2 × 2因子设计、III期、双盲、安慰剂对照、随机多中心临床试验，以检验口服强的松和伐昔洛韦的有效性和安全性。主要终点是6个月时的恢复率，由经过验证的连续变量Sunnybrook， Toronto， Facial Grading System测量。最小临床重要差异（MCID = 10）估计为Sunnybrook量表标准偏差（SD=20）的%。主要目的是确定这两种干预措施的安全性和有效性。假设#1：与不使用强的松相比，使用强的松会使永久性瘫的程度有临床和随机显著的降低。假设#2：与不使用valacyclovir相比，使用valacyclovir将获得永久性麻痹程度的临床和随机显著性降低。将探讨药物相互作用。第二个目的是利用贝尔麻痹患者丰富的前瞻性方案驱动数据来确定与结果相关的具体预后因素。假设：某些基线和早期病程预后因素，而不是治疗，与结果有关系。长期目标是确定未经治疗的结果水平，目前选择的贝尔氏麻痹治疗方法的治疗效果，以及未来转化和以患者为导向的研究的研究参数，并激发更大的科学兴趣，包括对这一重要“孤儿疾病”机制的临床和基础研究。修订后的计划拨款申请是为了支持多中心试验的必要准备工作。

DESCRIPTION (provided by applicant): Bell's palsy, the sudden onset of unilateral facial paralysis without identifiable cause involving all branches of the facial nerve, affects approximately 23/100,000 people each year. Herpes simplex virus, type 1, is the putative etiology. Intuition has led to the use of anti-inflammatories, principally oral prednisone, in combination with an oral antiviral, such as acyclovir or its pro-drug, valacyclovir. Prior efforts to investigate the effects of anti-inflammatory and antiviral interventions for Bell's palsy have been hampered by poor study design, differing inclusion criteria, and varying ordinal definitions of endpoint. These methodological problems have prevented the scientific assessment of the effectiveness of these interventions and led to widely different estimates of outcome. As a result, the most widely cited statistic that 71 % of untreated subjects recover to normal seems erroneous and insupportable. There is some evidence that as few as 24% recover completely to normal and that the remainder is permanently affected, 16% having significant disfigurement. Additionally, there is some evidence to suggest harm might occur or that recovery may be impeded by these agents. We propose to conduct a 2 x 2 factorial design, phase III, double blind, placebo- controlled, randomized multicenter clinical trial in 300 total subjects to test the efficacy and safety of orally administered prednisone and valacyclovir. The primary endpoint is the recovery rates at 6 months as measured by the validated continuous variable Sunnybrook, Toronto, Facial Grading System. A minimal clinically important difference (MCID = 10) is estimated to be % of the standard deviation (SD=20) of the Sunnybrook scale. The primary aim is to determine the safety and efficacy of these two interventions. Hypothesis #1: A small clinically and stochastically significant decrease in the degree of permanent paresis will be obtained with the use of prednisone when compared to non-use of prednisone. Hypothesis #2: A small clinically and stochastically significant decrease in the degree of permanent paresis will be obtained with the use of valacyclovir when compared to non-use of valacyclovir. Drug interactions will be explored. The secondary aim is to use this rich collection of prospective protocol driven data on Bell's palsy subjects to determine specific prognostic factors associated with outcomes. Hypothesis: Certain baseline and early course prognostic factors, and not treatments, have a relationship with outcomes. The long-term objectives are to determine untreated outcome levels, the therapeutic efficacy of the current treatments of choice in Bell's palsy, and study parameters for future translational and patient-oriented research, and to stimulate greater scientific interest, both in clinical and basic research into the mechanisms of this important "orphan disease." This revised planning grant application is to support necessary preparation for the multicenter trial.