Bell's Palsy-Randomized Clinical Trial

描述（由申请人提供）：贝尔麻痹，突然发生的单侧面瘫，没有可识别的原因，涉及面神经的所有分支，每年影响大约23/100，000人。单纯疱疹病毒1型是假定的病因。直觉已经导致使用抗炎药，主要是口服泼尼松，与口服抗病毒药物，如阿昔洛韦或其前药伐昔洛韦联合使用。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了不良研究设计、不同入选标准和终点不同顺序定义的阻碍。这些方法问题阻碍了对这些干预措施的有效性进行科学评估，并导致对结果的估计大相径庭。因此，最广泛引用的统计数据，即71%的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，这些制剂可能会造成伤害或阻碍恢复。我们拟在300例受试者中进行2 × 2析因设计、III期、双盲、安慰剂对照、随机多中心临床试验，以检测口服泼尼松和伐昔洛韦的疗效和安全性。主要终点是通过经验证的连续变量Sunnybrook，多伦多，面部分级系统测量的6个月时的恢复率。最小临床重要差异（MCID = 10）估计为Sunnybrook量表标准差（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：与未使用泼尼松相比，使用泼尼松可使永久性轻瘫程度出现临床和随机显著性小幅降低。假设#2：与不使用伐昔洛韦相比，使用伐昔洛韦可使永久性轻瘫程度在临床上和随机学上显著降低。将探索药物相互作用。第二个目的是使用这一丰富的前瞻性协议驱动的数据收集贝尔麻痹的主题，以确定特定的预后因素与结果。假设：某些基线和早期预后因素，而不是治疗，与结果有关。长期目标是确定未治疗的结果水平，当前贝尔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，无论是在临床和基础研究中，这种重要的“孤儿病”的机制。“这项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。

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.