Trial Outcomes & Findings for Impact of Nuedexta on Bulbar Physiology and Function in ALS (NCT NCT03883581)
NCT ID: NCT03883581
Last Updated: 2023-03-08
Results Overview
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).
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
28 participants
Primary outcome timeframe
Baseline; Day 30
Results posted on
2023-03-08
Participant Flow
All recruitment and enrollment took place at the Phil Smith Neuroscience Institute. Recruitment began in July 25, 2019 and ended in August 2021
Participant milestones
| Measure |
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.
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 Study
STARTED
|
28
|
|
Overall Study
COMPLETED
|
24
|
|
Overall Study
NOT COMPLETED
|
4
|
Reasons for withdrawal
| Measure |
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.
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 Study
Withdrawal by Subject
|
4
|
Baseline Characteristics
Impact of Nuedexta on Bulbar Physiology and Function in ALS
Baseline characteristics by cohort
| Measure |
ALS Individuals With Bulbar Dysfunction
n=28 Participants
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.
|
|---|---|
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Age, Categorical
<=18 years
|
0 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
12 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
16 Participants
n=5 Participants
|
|
Age, Continuous
|
64.75 years
STANDARD_DEVIATION 9.18 • n=5 Participants
|
|
Sex: Female, Male
Female
|
11 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
17 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
26 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
3 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
2 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
28 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline; Day 30The 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).
Outcome measures
| Measure |
ALS Individuals With Bulbar Dysfunction
n=24 Participants
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.
|
|---|---|
|
Change in Dynamic Imaging Grade of Swallowing Toxicity
Pre Nuedexta DIGEST 0 (Normal)
|
3 Participants
|
|
Change in Dynamic Imaging Grade of Swallowing Toxicity
Post Nuedexta DIGEST 0 (Normal)
|
7 Participants
|
PRIMARY outcome
Timeframe: Baseline; Day 30The 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.
Outcome measures
| Measure |
ALS Individuals With Bulbar Dysfunction
n=25 Participants
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.
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|---|---|
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Change in Speech Intelligibility
Pre Nuedexta
|
71.52 Percent Intelligibility
Standard Error 6.62
|
|
Change in Speech Intelligibility
Post Nuedexta
|
73.06 Percent Intelligibility
Standard Error 6.15
|
PRIMARY outcome
Timeframe: Baseline; Day 30The 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).
Outcome measures
| Measure |
ALS Individuals With Bulbar Dysfunction
n=25 Participants
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.
|
|---|---|
|
Change in Patient-reported Outcome: Center for Neurologic Study-Bulbar Function Scale (CNS-BFS)
Pre Nuedexta
|
56.87 Score
Standard Error 3.01
|
|
Change in Patient-reported Outcome: Center for Neurologic Study-Bulbar Function Scale (CNS-BFS)
Post Nuedexta
|
54.13 Score
Standard Error 2.97
|
PRIMARY outcome
Timeframe: Baseline; Day 30The 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.
Outcome measures
| Measure |
ALS Individuals With Bulbar Dysfunction
n=25 Participants
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.
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|---|---|
|
Change in ALSFRS-R Bulbar Subscale Score
Pre Nuedexta
|
7.47 score on a scale
Standard Error 0.38
|
|
Change in ALSFRS-R Bulbar Subscale Score
Post Nuedextaa
|
8.39 score on a scale
Standard Error 0.37
|
PRIMARY outcome
Timeframe: Baseline; Day 30The Bamboo Passage is a 60-word reading passage that is commonly used to measure speech duration.
Outcome measures
| Measure |
ALS Individuals With Bulbar Dysfunction
n=25 Participants
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.
|
|---|---|
|
Bamboo Passage Reading Duration (in Seconds)
Pre Nuedexta
|
66.19 Seconds
Standard Error 3.59
|
|
Bamboo Passage Reading Duration (in Seconds)
Post Nuedexta
|
65.33 Seconds
Standard Error 3.59
|
Adverse Events
ALS Individuals With Bulbar Dysfunction
Serious events: 1 serious events
Other events: 4 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
ALS Individuals With Bulbar Dysfunction
n=28 participants at risk
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.
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|---|---|
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General disorders
Prolonged hospitalization due to left leg DVT
|
3.6%
1/28 • Number of events 1 • Adverse events were collected from time of enrollment to study trial completion (30 days).
|
Other adverse events
| Measure |
ALS Individuals With Bulbar Dysfunction
n=28 participants at risk
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.
|
|---|---|
|
General disorders
Fainting
|
3.6%
1/28 • Number of events 1 • Adverse events were collected from time of enrollment to study trial completion (30 days).
|
|
Gastrointestinal disorders
Diarrhea
|
3.6%
1/28 • Number of events 1 • Adverse events were collected from time of enrollment to study trial completion (30 days).
|
|
General disorders
Headache
|
3.6%
1/28 • Number of events 1 • Adverse events were collected from time of enrollment to study trial completion (30 days).
|
|
General disorders
Nausea
|
3.6%
1/28 • Number of events 1 • Adverse events were collected from time of enrollment to study trial completion (30 days).
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place