- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03883581
Impact of Nuedexta on Bulbar Physiology and Function in ALS
November 23, 2021 updated by: University of Florida
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.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
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.
Study Type
Interventional
Enrollment (Actual)
28
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
-
Florida
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Fort Lauderdale, Florida, United States, 33308
- Phil Smith Neuroscience Institute at Holy Cross Hospital
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Gainesville, Florida, United States, 32610
- University of Florida
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years to 90 years (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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.
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ALS individuals with bulbar dysfunction
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.
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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:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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).
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Baseline; Day 30
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Change in Airway Physiologic Defense Capacity
Time Frame: Baseline; Day 30
|
Peak expiratory cough flow will be collected during maximum effort voluntary cough testing.
Peak expiratory cough flow is calculated as the flow rate (L/s/s) between the end point of the compression phase of cough to the point of maximum expiration.
Three trials will be performed at each evaluation and the maximum flow rate of the three epochs will be utilized for statistical analysis.
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Baseline; Day 30
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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.
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Baseline; Day 30
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Change in Patient-reported outcome: Center for Neurologic Study-Bulbar Function Scale (CNS-BFS)
Time Frame: Baseline; Day 30
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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 1-7 with 7 considered the worst, with total scores ranging from 21 (no impairment) - 112 (severe impairment in all domains).
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Baseline; Day 30
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Emily Plowman, PhD, University of Florida
- Principal Investigator: Lauren Tabor, PhD, Phil Smith Neuroscience Institute at Holy Cross Hospital
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start (Actual)
July 25, 2019
Primary Completion (Actual)
September 13, 2021
Study Completion (Actual)
November 22, 2021
Study Registration Dates
First Submitted
March 12, 2019
First Submitted That Met QC Criteria
March 19, 2019
First Posted (Actual)
March 21, 2019
Study Record Updates
Last Update Posted (Actual)
November 24, 2021
Last Update Submitted That Met QC Criteria
November 23, 2021
Last Verified
November 1, 2021
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Metabolic Diseases
- Central Nervous System Diseases
- Nervous System Diseases
- Neuromuscular Diseases
- Neurodegenerative Diseases
- Spinal Cord Diseases
- TDP-43 Proteinopathies
- Proteostasis Deficiencies
- Motor Neuron Disease
- Amyotrophic Lateral Sclerosis
- Physiological Effects of Drugs
- Adrenergic Antagonists
- Adrenergic Agents
- Neurotransmitter Agents
- Molecular Mechanisms of Pharmacological Action
- Anti-Arrhythmia Agents
- Anti-Infective Agents
- Muscarinic Antagonists
- Cholinergic Antagonists
- Cholinergic Agents
- Enzyme Inhibitors
- Excitatory Amino Acid Antagonists
- Excitatory Amino Acid Agents
- Membrane Transport Modulators
- Cytochrome P-450 Enzyme Inhibitors
- Voltage-Gated Sodium Channel Blockers
- Sodium Channel Blockers
- Cytochrome P-450 CYP2D6 Inhibitors
- Respiratory System Agents
- Antiprotozoal Agents
- Antiparasitic Agents
- Antimalarials
- Antitussive Agents
- Adrenergic alpha-Antagonists
- Dextromethorphan
- Quinidine
- Quinidine gluconate
Other Study ID Numbers
- IRB201802938
- OCR20392 (Other Identifier: UF OnCore)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
No
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Yes
Studies a U.S. FDA-regulated device product
No
product manufactured in and exported from the U.S.
Yes
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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