Impact of Nuedexta on Bulbar Physiology and Function in ALS

Study Purpose:

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.

Disease:

Amyotrophic Lateral Sclerosis (ALS),  Familial ALS,  Sporadic ALS

Study Type:

Interventional Trial

Study Category:

Drug Trial

Study Status:

Enrolling

Phase:

Phase I ,Phase II

Study Chair(s)/Principal Investigator(s):

Lauren Tabor, PhD Phil Smith Neuroscience Institute at Holy Cross Hospital
Emily Plowman, PhD University of Florida

Clinicaltrials.gov ID (11 digit #):

NCT03883581

Neals Affiliated?

No

Coordinating Center Contact Information

University of Florida
Lauren DiBiase, MS / .(JavaScript must be enabled to view this email address) / 352-273-8632
.(JavaScript must be enabled to view this email address) Gainesville, Florida 32610 United States

Full Study Summary:

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.

Study Sponsor:

University of Florida

Participant Duration:

Estimated Enrollment:

40

Estimated Study Start Date:

07/25/2019

Estimated Study Completion Date:

02/28/2021

Posting Last Modified Date:

11/11/2019

Date Study Added to alsconsortium.org:

05/21/2019
  • Eligibility Criteria

    Gender:

    Female, Male

    Minimum Age:

    18

    Maximum Age:

    90

    Time since Symptom Onset:

    Time since Diagnosis:

    Can participants use Riluzole?

    Yes


    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.

  • Site Contact Information

    Phil Smith Neuroscience Institute at Holy Cross Hospital
    Lauren Tabor, PhD / .(JavaScript must be enabled to view this email address) / 954-542-3429
    Fort Lauderdale, Florida 33308
    United States

    University of Florida
    Lauren DiBiase, MS / .(JavaScript must be enabled to view this email address) / 352-273-8632
    Gainesville, Florida 32610
    United States