Impact of Nuedexta on Bulbar Physiology and Function in ALS

NCT03883581 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: IRB201802938OCR20392
• Study Type: interventional
• Target: 28
• Locations: 1 country
• Sites: 2

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.

Conditions

Amyotrophic Lateral Sclerosis

Keywords

bulbar dysfunction

Outcome Measures

Primary Outcomes (5)

• Change in Dynamic Imaging Grade of Swallowing Toxicity

  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).

  Baseline; Day 30

• Change in Speech Intelligibility

  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.

  Baseline; Day 30

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

  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).

  Baseline; Day 30

• Change in ALSFRS-R Bulbar Subscale Score

  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.

  Baseline; Day 30

• Bamboo Passage Reading Duration (in Seconds)

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

  Baseline; Day 30

Study Arms (1)

ALS individuals with bulbar dysfunction

EXPERIMENTAL

Participants enrolled in this group will be prescribed dextromethorphan HBr and quinidine sulfate (Nuedexta) as recommended by their treating neurologist. 20 mg dextromethorphan HBr and 10mg quinidine sulfate will be administered orally with 1 capsule every day for the initial 7 days followed by 1 capsule every 12 hours for the remaining 23 days of the study. Participants will be evaluated 30 days apart to determine the impact of treatment.

Drug: dextromethorphan HBr and quinidine sulfate

Interventions

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.

Also known as: Nuedexta

ALS individuals with bulbar dysfunction

Eligibility Criteria

• Age: 18 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Florida: lead
• Holy Cross Hospital, Florida: collaborator
• ALS Association: collaborator

Study Sites (2)

Phil Smith Neuroscience Institute at Holy Cross Hospital

Fort Lauderdale, Florida, 33308, United States

Location

University of Florida

Gainesville, Florida, 32610, United States

Location

MeSH Terms

Conditions

Amyotrophic Lateral Sclerosis

Interventions

Dextromethorphan; Quinidine; dextromethorphan - quinidine combination

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds; Cinchona Alkaloids; Quinuclidines; Quinolines; Heterocyclic Compounds, 2-Ring

Results Point of Contact

• Title: Lauren Tabor Gray
• Organization: NOVA Southeastern University

Lauren.taborgray@nova.edu

954-914-5447

Study Officials

• Lauren Tabor, PhD

  Phil Smith Neuroscience Institute at Holy Cross Hospital

  PRINCIPAL INVESTIGATOR

• Emily Plowman, PhD

  University of Florida

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 12, 2019
• First Posted: March 21, 2019
• Study Start: July 25, 2019
• Primary Completion: September 13, 2021
• Study Completion: November 22, 2021
• Last Updated: March 8, 2023
• Results First Posted: March 8, 2023

Record last verified: 2023-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)