Impact of Nuedexta on Bulbar Physiology and Function in ALS

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.

Inclusion Criteria:

- Diagnosis of probable-definite ALS (El-Escorial Criterion);

- ALSFRS-R Bulbar subscale score <10

- Bamboo oral reading speaking rate <140 words per minute

- No allergies to barium sulfate.

Exclusion Criteria:

- Treatment for sialorrhea within the past 3 months that includes either Botox or
radiation treatment

- Participation in another disease modifying study targeting bulbar or cough function

- Use of invasive mechanical ventilation/presence of tracheostomy

- Advanced frontotemporal dementia or significant cognitive dysfunction

- Nil per oral status for feeding (i.e., NPO, nothing by mouth)

- Previously prescribed Nuedexta. Additionally, if participants are taking Riluzole or
other medications to control sialorrhea, they must be on a stable dose for at least 30
days prior to enrollment in the current study.