Bell's Palsy-Randomized Clinical Trial

Washington University, Saint Louis MO

Investigators

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Abstract

[unreadable] 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. [unreadable] [unreadable] [unreadable]