Impact of Nuedexta on Bulbar Physiology and Function in ALS

• ClinicalTrials.gov Identifier: NCT03883581
• Recruitment Status: Completed
• First Posted: March 21, 2019
• Results First Posted: March 8, 2023
• Last Update Posted: March 8, 2023
• Sponsor: University of Florida
• Collaborators: Holy Cross Hospital, Florida; ALS Association
• Information provided by (Responsible Party): University of Florida

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Amyotrophic Lateral Sclerosis
• Intervention: Drug: dextromethorphan HBr and quinidine sulfate
• Enrollment: 28

Participant Flow

Recruitment Details	All recruitment and enrollment took place at the Phil Smith Neuroscience Institute. Recruitment began in July 25, 2019 and ended in August 2021
Pre-assignment Details

Arm/Group Title	ALS Individuals With Bulbar Dysfunction
Arm/Group Description	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. 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.
Period Title: Overall Study
Started	28
Completed	24
Not Completed	4
Reason Not Completed
Withdrawal by Subject	4

Baseline Characteristics

Arm/Group Title		ALS Individuals With Bulbar Dysfunction
Arm/Group Description		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. 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.
Overall Number of Baseline Participants		28
Baseline Analysis Population Description		[Not Specified]
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	28 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	12 42.9%
	>=65 years	16 57.1%
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	28 participants
		64.75 (9.18)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	28 participants
	Female	11 39.3%
	Male	17 60.7%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	28 participants
	Hispanic or Latino	2 7.1%
	Not Hispanic or Latino	26 92.9%
	Unknown or Not Reported	0 0.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	28 participants
	American Indian or Alaska Native	0 0.0%
	Asian	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%
	Black or African American	3 10.7%
	White	23 82.1%
	More than one race	2 7.1%
	Unknown or Not Reported	0 0.0%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	28 participants
		28

Outcome Measures

1. Primary Outcome

Title	Change in Dynamic Imaging Grade of Swallowing Toxicity
Description	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).
Time Frame	Baseline; Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ALS Individuals With Bulbar Dysfunction
Arm/Group Description:	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. 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.
Overall Number of Participants Analyzed	24
Measure Type: Count of Participants; Unit of Measure: Participants
Pre Nuedexta DIGEST 0 (Normal)	3 12.5%
Post Nuedexta DIGEST 0 (Normal)	7 29.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALS Individuals With Bulbar Dysfunction
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.08
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

2. Primary Outcome

Title	Change in Speech Intelligibility
Description	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.
Time Frame	Baseline; Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ALS Individuals With Bulbar Dysfunction
Arm/Group Description:	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. 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.
Overall Number of Participants Analyzed	25
Mean (Standard Error); Unit of Measure: Percent Intelligibility
Pre Nuedexta	71.52 (6.62)
Post Nuedexta	73.06 (6.15)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALS Individuals With Bulbar Dysfunction
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.647
	Comments	[Not Specified]
	Method	Paired t test
	Comments	[Not Specified]

3. Primary Outcome

Title	Change in Patient-reported Outcome: Center for Neurologic Study-Bulbar Function Scale (CNS-BFS)
Description	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).
Time Frame	Baseline; Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ALS Individuals With Bulbar Dysfunction
Arm/Group Description:	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. 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.
Overall Number of Participants Analyzed	25
Mean (Standard Error); Unit of Measure: Score
Pre Nuedexta	56.87 (3.01)
Post Nuedexta	54.13 (2.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALS Individuals With Bulbar Dysfunction
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.103
	Comments	[Not Specified]
	Method	Paired t test
	Comments	[Not Specified]

4. Primary Outcome

Title	Change in ALSFRS-R Bulbar Subscale Score
Description	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.
Time Frame	Baseline; Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ALS Individuals With Bulbar Dysfunction
Arm/Group Description:	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. 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.
Overall Number of Participants Analyzed	25
Mean (Standard Error); Unit of Measure: score on a scale
Pre Nuedexta	7.47 (0.38)
Post Nuedextaa	8.39 (0.37)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALS Individuals With Bulbar Dysfunction
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.0004
	Comments	[Not Specified]
	Method	Wilcoxon (Mann-Whitney)
	Comments	[Not Specified]

5. Primary Outcome

Title	Bamboo Passage Reading Duration (in Seconds)
Description	The Bamboo Passage is a 60-word reading passage that is commonly used to measure speech duration.
Time Frame	Baseline; Day 30

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	ALS Individuals With Bulbar Dysfunction
Arm/Group Description:	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. 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.
Overall Number of Participants Analyzed	25
Mean (Standard Error); Unit of Measure: Seconds
Pre Nuedexta	66.19 (3.59)
Post Nuedexta	65.33 (3.59)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	ALS Individuals With Bulbar Dysfunction
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.103
	Comments	[Not Specified]
	Method	Paired t test
	Comments	[Not Specified]

Adverse Events

Time Frame	Adverse events were collected from time of enrollment to study trial completion (30 days).
Adverse Event Reporting Description	[Not Specified]
Arm/Group Title	ALS Individuals With Bulbar Dysfunction
Arm/Group Description	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. 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.
All-Cause Mortality
	ALS Individuals With Bulbar Dysfunction
	Affected / at Risk (%)
Total	0/28 (0.00%)
Serious Adverse Events
	ALS Individuals With Bulbar Dysfunction
	Affected / at Risk (%)	# Events
Total	1/28 (3.57%)
General disorders
Prolonged hospitalization due to left leg DVT * [1]	1/28 (3.57%)	1
* Indicates events were collected by non-systematic assessment; [1] The subject was hospitalized for three days and treated for left leg DVT (unrelated to the study drug). The subject was treated accordingly and discharged home.
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	ALS Individuals With Bulbar Dysfunction
	Affected / at Risk (%)	# Events
Total	4/28 (14.29%)
Gastrointestinal disorders
Diarrhea * [1]	1/28 (3.57%)	1
General disorders
Fainting * [2]	1/28 (3.57%)	1
Headache * [3]	1/28 (3.57%)	1
Nausea * [4]	1/28 (3.57%)	1
* Indicates events were collected by non-systematic assessment; [1] The subject reported diarrhea for three days, possibly related to the study drug. The subject continued participating in the study.; [2] The subject reported a fainting episode, possibly related to the study drug. The subject discontinued participation in the study following this episode.; [3] The study subject reported headaches over two days with a probable relationship to the study drug. The subject discontinued participation in the study.; [4] The subject reported nausea for two days with a probable relationship to the study drug. The subject discontinued participation in the study.

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Lauren Tabor Gray
• Organization: NOVA Southeastern University
• Phone: 954-914-5447
• EMail: Lauren.taborgray@nova.edu

• Responsible Party: University of Florida
• ClinicalTrials.gov Identifier: NCT03883581
• Other Study ID Numbers: IRB201802938; OCR20392 ( Other Identifier: UF OnCore )
• First Submitted: March 12, 2019
• First Posted: March 21, 2019
• Results First Submitted: September 12, 2022
• Results First Posted: March 8, 2023
• Last Update Posted: March 8, 2023