Impact of Nuedexta on Bulbar Physiology and Function in ALS
Condition: Amyotrophic Lateral Sclerosis
MeSH terms: Motor Neuron Disease; Amyotrophic Lateral Sclerosis
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      Nuedexta is FDA approved for the treatment of pseudobulbar affect in ALS patients and
      anecdotal reports of improvements in speech, salivation or swallowing have been reported.
      However, no prospective study has been conducted to comprehensively examine and determine the
      physiologic impact of Nuedexta on both speech and swallowing physiology in a large group of
      ALS individuals. These data are needed in order to provide evidence-based guidance to the
      management of bulbar dysfunction in ALS.
    

Detailed description: 
      Although advances in the management of bulbar dysfunction in ALS have been disappointing,
      recent interest has surfaced regarding the therapeutic potential of a pharmaceutical agent,
      Nuedexta (dextromethorphan HBr and quinidine sulfate), for the treatment of bulbar
      symptomology in individuals with ALS. Although Nuedexta received approval from the Food and
      Drug Administration (FDA) to target symptoms of pseudobulbar affect (PBA) in ALS; anecdotal
      reports of improvements in speech, salivation or swallowing were reported from Neurologists
      treating ALS individuals who were administered Nuedexta. Subsequently, a Phase II clinical
      trial was conducted that reported improvements in speech, swallowing and salivation following
      30-days of Nuedexta treatment. One serious limitation of this study, however, is the fact
      that the primary outcome employed was a perceptual patient-report scale (PRO) (Center for
      Neurological Study Bulbar Function Scale, CNS-BFS), with no objective physiologic outcomes to
      confirm actual change in bulbar physiology. The absence of any objective clinical physiologic
      outcomes is particularly important when examining effects of Nuedexta, given that it contains
      selective serotonin reuptake inhibitors (SSRIs), or serotonergic antidepressants, that can
      impact the regulation of emotional expression, feelings of wellbeing and modulation of
      depression (all known to impact the response an individual will provide on a PRO measure).
      Furthermore, findings based on PRO's must be validated with studies that utilize objective
      physiologic outcomes of speech and swallowing function. Great excitement exists regarding the
      potential impact of Nuedexta on bulbar function in ALS with many neurologists prescribing
      Nuedexta to treat these symptoms in ALS patients. To date, however; no data exists to examine
      and determine the physiologic impact of Nuedexta on speech or swallowing physiology. These
      data are needed in order to validate the initial patient-reported outcomes of the Phase II
      clinical trial and to provide evidence-based guidance to the management of bulbar dysfunction
      in ALS.
    

Intervention name(s): dextromethorphan HBr and quinidine sulfate
Intervention type(s): Drug
Intervention description(s): All eligible and enrolled study participants will be administered the study drug, Nuedexta, as recommended by their treating neurologists.The drug will be administered per the efficacy and safety protocol, with no changes in administration method or recommended dose for individuals with ALS. Prior to commencing treatment with Nuedexta, participants will undergo a comprehensive bulbar evaluation of swallowing, airway protection, speech functions, and complete validated patient-reported surveys. Following 30 days of Nuedexta treatment, participants will be e-evaluated using the same battery of assessments.
Other intervention name(s): Nuedexta
Intervention MeSH terms: Quinidine; Quinidine gluconate; Dextromethorphan
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: bulbar dysfunction