Enhanced Bulbar Function in Amyotrophic Lateral Sclerosis: The Nuedexta Treatment Trial

Abstract

The goal of this randomized, blinded, crossover clinical trial was to determine whether Nuedexta (dextromethorphan and quinidine) enhanced speech, swallowing, and salivation in patients with ALS. Sixty patients with amyotrophic lateral sclerosis (ALS) received either Nuedexta or placebo for 28 to 30 days, followed by a 10 to 15-day washout period. Subsequently, patients were switched to the opposite treatment arm for the remaining days of the trial. The primary endpoint was a reduction in the self-report Center for Neurologic Study Bulbar Function Scale (CNS-BFS) score. The rater-administered ALS Functional Rating Scale Revised was the principal secondary endpoint. The CNS-BFS score improved with active treatment, decreasing from a mean of 59.3 in the placebo arm of the trial to 53.5 during the drug-treatment arm (p < 0.001). Each of the individual domains of bulbar function interrogated by the CNS-BFS responded to treatment with Nuedexta as follows: salivation: 15.8 versus 14.3 (p = 0.004); speech: 24.6 versus 22.2 (p = 0.003); swallowing: 18.9 versus 17.1 (p = 0.009). Similarly, the bulbar component of the ALS Functional Rating Scale Revised improved with active treatment (p = 0.003), although the drug did not affect the motor and respiratory components of this scale. This study is unique for several reasons. Firstly, it was driven by patient reports of improved speech and swallowing while taking Nuedexta for control of emotional lability. Secondly, the study was conducted over a short duration (70 days), and thirdly, a self-report scale was selected as the principle outcome measure. Considering the importance of bulbar functions, these results, if confirmed, point to an additional use of Nuedexta as an adjunct to the management of ALS.

Keywords: Amyotrophic lateral sclerosis; Nuedexta; bulbar function; clinical trial; dextromethorphan; self-report scale.

Fig. 1

Study design

Fig. 2

CONSORT diagram. DMQ = Nuedexta; AE = adverse event

Fig. 3

Effect of Nuedexta (DMQ) versus placebo on changes in the Center for Neurologic Study Bulbar Function Scale (CNS-BFS; primary outcome measure). (A) Mean CNS-BFS scores for each treatment arm (i.e., patients treated with placebo first and then switched to DMQ vs patients placed on DMQ initially and later switched to placebo) were calculated during the course of the clinical trial. Measurements were obtained at baseline, and during 3 subsequent clinical visits. For the group treated with placebo initially, DMQ treatment was initiated following visit 2 and the drug treatment effect measured at visit 3. For the group treated with DMQ initially, drug treatment began immediately following the baseline visit and the effect of treatment was measured at visit 1. The crossover effect is apparent: CNS-BFS scores declined following the period of DMQ treatment. (B) Histogram of unadjusted treatment-dependent change in CNS-BFS total scores among completers. Negative values indicate larger reductions in CNS-BFS total scores after receiving DMQ. Positive values indicate larger reductions after receiving placebo. (C) Interaction plot of CNS-BFS versus pseudobulbar affect (PBA) status. Improvement in bulbar function (CNS-BFS) associated with DMQ treatment stratified by presence or absence of PBA at baseline, defined by a score > 13 on the Center for Neurologic Study Emotional Lability Scale (CNS-LS). Mean baseline-adjusted CNS-BFS total scores ± 95% confidence intervals (CI) are displayed on the y-axis. DMQ treatment improved bulbar functioning irrespective of whether patients had PBA