Impact of Nuedexta on Bulbar Physiology and Function in ALS

NCT ID: NCT03883581

Last Updated: 2023-03-08

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 28 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-07-25
• Study Completion Date: 2021-11-22

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.

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.

Conditions

Amyotrophic Lateral Sclerosis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

dextromethorphan HBr and quinidine sulfate

Intervention Type: 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.

Interventions

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.

Intervention Type: DRUG

Other Intervention Names

Nuedexta

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 90 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Holy Cross Hospital, Florida

OTHER

Sponsor Role: collaborator

ALS Association

OTHER

Sponsor Role: collaborator

University of Florida

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lauren Tabor, PhD

Role: PRINCIPAL_INVESTIGATOR

Phil Smith Neuroscience Institute at Holy Cross Hospital

Emily Plowman, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

Phil Smith Neuroscience Institute at Holy Cross Hospital

Fort Lauderdale, Florida, United States

University of Florida

Gainesville, Florida, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

OCR20392

Identifier Type: OTHER

Identifier Source: secondary_id

IRB201802938

Identifier Type: -

Identifier Source: org_study_id