Impact of Nuedexta on Bulbar Physiology and Function in ALS

Amyotrophic Lateral Sclerosis Clinical Trial

Official title:

Impact of Nuedexta on Bulbar Physiology and Function in ALS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03883581
• Other study ID #: IRB201802938
• Secondary ID: OCR20392
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: July 25, 2019
• Est. completion date: November 22, 2021

Study information

• Verified date: February 2023
• Source: University of Florida
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 28
• Est. completion date: November 22, 2021
• Est. primary completion date: September 13, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 90 Years

Eligibility

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.

Related Conditions & MeSH terms

• Amyotrophic Lateral Sclerosis
• Motor Neuron Disease

Intervention

Drug:
• dextromethorphan HBr and quinidine sulfate
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.

Locations

Country	Name	City	State
United States	Phil Smith Neuroscience Institute at Holy Cross Hospital	Fort Lauderdale	Florida
United States	University of Florida	Gainesville	Florida

Sponsors (3)

Lead Sponsor	Collaborator
University of Florida	ALS Association, Holy Cross Hospital, Florida

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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