Clinical trial NCT03883581: Impact of Nuedexta on Bulbar Physiology and Function in ALS
Official title: Impact of Nuedexta on Bulbar Physiology and Function in ALS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Amyotrophic Lateral Sclerosis
Keywords: bulbar dysfunction
Lead sponsor: University of Florida
Sponsor class: OTHER
Collaborators: name: Holy Cross Hospital, Florida
name: ALS Association
First posted: 2019-03-21
Enrollment: 28
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Change in Dynamic Imaging Grade of Swallowing Toxicity
timeFrame: Baseline; Day 30
measure: Change in Speech Intelligibility
timeFrame: Baseline; Day 30
measure: Change in Patient-reported Outcome: Center for Neurologic Study-Bulbar Function Scale (CNS-BFS)
timeFrame: Baseline; Day 30
measure: Change in ALSFRS-R Bulbar Subscale Score
timeFrame: Baseline; Day 30
measure: Bamboo Passage Reading Duration (in Seconds)
timeFrame: Baseline; Day 30
Secondary outcomes:
Other outcomes:
Locations:
city: Fort Lauderdale
country: United States
facility: Phil Smith Neuroscience Institute at Holy Cross Hospital
state: Florida
city: Gainesville
country: United States
facility: University of Florida
state: Florida
Study officials:
affiliation: Phil Smith Neuroscience Institute at Holy Cross Hospital
name: Lauren Tabor, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Florida
name: Emily Plowman, PhD
role: PRINCIPAL_INVESTIGATOR
References: