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Completed

NCT Number: NCT03883581

Impact of Nuedexta on Bulbar Physiology and Function in ALS

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.

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Key information

Conditions

Amyotrophic Lateral Sclerosis Central Nervous System Diseases Metabolic Diseases Motor Neuron Disease Nervous System Diseases Neurodegenerative Diseases Neuromuscular Diseases Nutritional and Metabolic Diseases Proteostasis Deficiencies Spinal Cord Diseases TDP-43 Proteinopathies

Age range

18 year–90 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Phil Smith Neuroscience Institute at Holy Cross Hospital, Fort Lauderdale, Florida, United States

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About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

dextromethorphan HBr and quinidine sulfate

Drug

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 names: Nuedexta

Primary outcomes

  1. Change in Dynamic Imaging Grade of Swallowing Toxicity

    Time frame: Baseline; Day 30

    The validated Dynamic Imaging Grade of Swallowing Toxicity (DIGEST) will be performed on all collected videofluoroscopic swallowing studies to assess global swallowing function. The DIGEST total score is determined using the composite of individual airway safety and bolus efficiency subscores (range: 0-4). The DIGEST total is rated on a 5-point ordinal score ranging from 0 (no dysphagia) to 4 (life-threatening dysphagia).

  2. Change in Speech Intelligibility

    Time frame: Baseline; Day 30

    The Sentence Intelligibility Test (SIT) will be performed to assess the change in speaking intelligibility over the 30 day period. The primary outcome of the SIT will be the percentage of sentence intelligibility (%) during oral reading.

  3. Change in Patient-reported Outcome: Center for Neurologic Study-Bulbar Function Scale (CNS-BFS)

    Time frame: Baseline; Day 30

    The CNS-BFS is a validated patient-reported scale that assess self-reported impairments in the domains of speech, salivation and swallowing. Each domain contains 7 questions with ratings ranging from 1-5 with 5 considered the worst. For the speech domain, individuals who are unable to speak are assigned a value of 6 for each item (speech domain ranges from 1-6). Total scores ranging from 21 (no impairment) - 112 (severe impairment in all domains).

  4. Change in ALSFRS-R Bulbar Subscale Score

    Time frame: Baseline; Day 30

    The ALS Functional Rating Scale-Revised Bulbar subscore is an outcome comprised of questions 1-3 on the validated ALSFRS-R scale. These items rate speech, swallowing and salivation functions on a scale from 0-total loss of function to 4- no symptoms for a total score of 0 to 12.

  5. Bamboo Passage Reading Duration (in Seconds)

    Time frame: Baseline; Day 30

    The Bamboo Passage is a 60-word reading passage that is commonly used to measure speech duration.

Sponsors and collaborators

Lead sponsor

University of Florida

Other

Collaborators

  • ALS Association
  • Holy Cross Hospital, Florida

Registry information

Important dates

Study start
2019
Primary completion
2021
Study completion
2021
First posted
Mar 21, 2019
Registry last updated
Mar 8, 2023

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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