Spasmodic Dysphonia, Voice Tremor
Conditions
Keywords
spasmodic dysphonia, laryngeal dystonia, functional MRI, Xyrem
Brief summary
Using a comprehensive approach of clinico-behavioral testing, neuroimaging and pharmacogenetics, the researchers will examine the clinical effects of sodium oxybate and the matched placebo on voice symptoms in spasmodic dysphonia and voice tremor.
Detailed description
Spasmodic dysphonia (SD), or laryngeal dystonia, is a chronic debilitating condition that selectively affects speech production due to involuntary spasms in the laryngeal muscles. SD often extends beyond the impairment of vocal communication causing significant occupational disability and life-long social isolation. SD becomes even more incapacitating when it is associated with dystonic voice tremor (VT), which is present in about 1/3 of SD patients and is characterized by the inability to sustain a vowel for more than a few seconds. Current treatment of these disorders is limited to the temporary management of voice symptoms with repeated injections of botulinum toxin into the laryngeal muscles. These injections, however, are not fully effective in all SD patients and even less so in combined SD and VT cases. There is, therefore, a critical need to identify alternative therapeutic options that specifically target the pathophysiology of these disorders. On the other hand, the design and the use of such novel therapeutic approaches will be largely unattainable if their central mechanisms of action remain unknown. The objective of this study is to elucidate the primary determinants of clinical response to a novel oral medication, sodium oxybate (Xyrem®), in alcohol-responsive SD and VT patients. Using a comprehensive approach of clinico-behavioral testing, neuroimaging and pharmacogenetics, we aim to determine the clinical response of SD and VT symptoms to sodium oxybate and identify the primary markers of its clinical benefits. This study will use a controlled experimental design that focuses on detailed characterization of primary effects of a novel oral medication, sodium oxybate, for treatment of SD and VT symptoms.
Interventions
DRUGSodium Oxybate
Alcohol challenge test and oral administration of a single dose of sodium oxybate and the matching placebo.
Sponsors
National Institute on Deafness and Other Communication Disorders (NIDCD)
Kristina Simonyan
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Patients with SD and combined SD and VT will have a clinically documented adductor or abductor form of disorder, either with or without positive effects of alcohol on their voice symptoms; 2. Healthy controls will be healthy volunteers with a negative history of laryngeal, neurological, or psychiatric problems (existing neuroimaging data will be used); 3. Age from 21 to 80 years. 4. Native English speakers. 5. Right-handedness (based on Edinburgh Handedness Inventory).
Exclusion criteria
1. Subjects who are incapable of giving an informed consent will be excluded from the study. 2. Pregnant and breastfeeding women until a time when they are no longer pregnant or breastfeeding will be excluded from the study. All patients of childbearing potential will be required to agree to use a reliable method of contraception prior to and during the study. The method of contraception will be documented in the patient's research chart. All women of childbearing potential will undergo a urine pregnancy test, which must be negative for study participation. 3. All patients with a past or present history of the following conditions will be excluded from the study; 1. Except for SD and dystonic VT, any neurological disorders, such as stroke, movement disorders, brain tumors, traumatic brain injury with loss of consciousness, ataxias, myopathies, myasthenia gravis, demyelinating diseases, alcoholism, drug dependence. Patients with tremor affecting other body parts will be excluded from the study. All patients who have dystonic movements in the body regions other than the larynx will be excluded from the study. This will allow maintaining the homogenous patient population and evaluating central drug effects without confounding by the presence of other neurological conditions. 2. Any psychiatric problems, such as schizophrenia, major and/or bipolar depression, obsessive-compulsive disorder, will be excluded to maintain the homogenous patient population and allow for the evaluation of central drug effect without confounding by the presence of psychiatric conditions. 3. Any laryngeal problems, such as vocal fold paralysis, paresis, carcinoma, chronic laryngitis, will be excluded from the study. 4. Patients with a known past or present history of grade 2 or higher hepatic and renal dysfunction according to the NCI criteria will be excluded. 5. Patients with a known past or present history of moderate to severe congestive heart failure will be excluded. 6. Patients with a known past or present history of cognitive impairment and active suicidal ideations will be excluded. 4. Patients who are not symptomatic due to treatment with botulinum toxin injections into the laryngeal muscles will be excluded from the study until the time when they are fully symptomatic. The duration of positive effects of botulinum toxin vary from patient to patient, lasting on average 3-4 months. All patients will be evaluated to ensure that they are fully symptomatic prior to the entering the study. 5. To avoid the possibility of confounding effects of drugs acting upon the central nervous system, all patients will be questioned about any prescribed or over-the-counter medications as part of their initial intake screening. Those patients who receive medication(s) affecting the central nervous system (except for sodium oxybate) will be excluded from the study. 6. Patients will be asked whether they have undergone any head and neck surgeries, particularly any brain surgery and laryngeal surgeries, such as thyroplasty, laryngeal denervation, and selective laryngeal adductor denervation-reinnervation. Because both brain and laryngeal surgery may potentially lead to the brain structure and function re-organization, all subjects with a history of brain and/or laryngeal surgery will be excluded from the study. 7. Patients who have tattoos, ferromagnetic objects in their bodies (e.g., implanted stimulators, surgical clips, prosthesis, artificial heart valve, etc.) that are not MRI comparable and/or cannot be removed for the purpose of MRI study participation will be excluded from the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Symptom Severity | 40 min after drug or placebo administration | A combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity before and after drug vs. placebo intake. For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group. |
| Minimum Treatment Efficacy | 40 min after drug or placebo administration | Pre-specified to analysis based only on alcohol responsiveness (EtOH+). A combined clinician-objective and patient-subjective change in visual analog scale score (min-max 0-100, a higher score is the worse outcome) of symptom severity in EtOH+ patients. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Treatment Efficacy Dependent on LD Clinical Type | 40 min after drug or placebo administration | A combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity before and after drug vs. placebo intake. EtOH+ and EtOH- were stratified based on phenotypical characteristics, including LD, LD with Dystonic Tremor of Voice, Abductor LD, Adductor LD. |
| Length of Treatment Efficacy | 40 min to 5 hours after drug or placebo administration | The length of treatment efficacy in each EtOH+ and EtOH- group was assessed at 40, 180, and 300 min after drug vs. placebo intake compared to the baseline using a combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity. For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group. |
| Relationship Between Alcohol-responsiveness of Symptoms and Drug-induced Symptom Improvement | 40 min after drug or placebo administration | A combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity before and 40 min after drug vs. placebo intake. For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group. |
| Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics | 40 min after drug or placebo administration | A combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity before and 40 min after drug vs. placebo intake. For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group. |
Countries
United States
Participant flow
Recruitment details
The study was conducted between January 22, 2018, and December 29, 2021. The COVID-19 pandemic and the associated lockdown of human research activities fully paused patient recruitment and the conduct of study procedures between March 2020 and December 2020.
Pre-assignment details
Pre-specified to LD patients with and without dystonic voice tremor regardless of alcohol responsiveness of symptoms. 9 patients were excluded because of a history of suicidal ideations (n= 3), absence of symptoms at the time of study participation (n= 3), left-handedness (n= 1), presence of multifocal dystonia (n= 1), and contraindications to MRI (n= 1).
Participants by arm
| Arm | Count |
|---|---|
| (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. | 23 |
| (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia With Dystonic Tremor of Voice For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. | 29 |
| (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group. | 30 |
| (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia With Dystonic Tremor of Voice For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group. | 26 |
| Total | 108 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 1 | Adverse Event | 2 | 0 |
Baseline characteristics
| Characteristic | (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia With Dystonic Tremor of Voice | Total | (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia | (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia With Dystonic Tremor of Voice | (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 14 Participants | 38 Participants | 4 Participants | 13 Participants | 7 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 70 Participants | 19 Participants | 16 Participants | 23 Participants |
| Age, Continuous | 66.5 years | 59.5 years | 56.0 years | 62.0 years | 57.0 years |
| Age of onset | 46.5 years | 44.0 years | 38.0 years | 50.0 years | 43.5 years |
| Botulinum toxin treatment | 21 Participants | 93 Participants | 20 Participants | 26 Participants | 26 Participants |
| Centrally acting medications | 5 Participants | 24 Participants | 4 Participants | 8 Participants | 7 Participants |
| Cognitive function < 26 points (impaired cognitive function) | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Cognitive function ≥ 26 points (normal cognitive function) | 26 Participants | 108 Participants | 23 Participants | 29 Participants | 30 Participants |
| Dystonia duration | 13.4 years | 13.0 years | 13.0 years | 13.0 years | 11.0 years |
| Dystonia phenotype Abductor type | 9 Participants | 43 Participants | 10 Participants | 12 Participants | 12 Participants |
| Dystonia phenotype Adductor type | 16 Participants | 58 Participants | 12 Participants | 13 Participants | 17 Participants |
| Dystonia phenotype Mixed adductor and abductor type | 1 Participants | 7 Participants | 1 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 26 Participants | 108 Participants | 23 Participants | 29 Participants | 30 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Family history of dystonia Familial type | 1 Participants | 8 Participants | 3 Participants | 2 Participants | 2 Participants |
| Family history of dystonia Sporadic type | 25 Participants | 100 Participants | 20 Participants | 27 Participants | 28 Participants |
| Handedness Left-handed | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Handedness Right-handed | 26 Participants | 108 Participants | 23 Participants | 29 Participants | 30 Participants |
| Monolingual native English Language | 26 Participants | 108 Participants | 23 Participants | 29 Participants | 30 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 2 Participants | 7 Participants | 3 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 24 Participants | 101 Participants | 20 Participants | 28 Participants | 29 Participants |
| Sex: Female, Male Female | 18 Participants | 76 Participants | 15 Participants | 26 Participants | 17 Participants |
| Sex: Female, Male Male | 8 Participants | 32 Participants | 8 Participants | 3 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 50 | 0 / 50 | 0 / 56 | 0 / 56 |
| other Total, other adverse events | 29 / 50 | 8 / 50 | 37 / 56 | 13 / 56 |
| serious Total, serious adverse events | 0 / 50 | 0 / 50 | 0 / 56 | 0 / 56 |
Outcome results
Primary
Minimum Treatment Efficacy
Pre-specified to analysis based only on alcohol responsiveness (EtOH+). A combined clinician-objective and patient-subjective change in visual analog scale score (min-max 0-100, a higher score is the worse outcome) of symptom severity in EtOH+ patients.
Time frame: 40 min after drug or placebo administration
Population: Pre-specified to only report Alcohol-responsive (EtOH+) Laryngeal Dystonia Arm
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Minimum Treatment Efficacy | Symptom improvement ≥ 16% | 40.81 percentage of symptom change |
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Minimum Treatment Efficacy | Symptom improvement < 16% | 4.76 percentage of symptom change |
Comparison: The minimum and average efficacy of sodium oxybate vs. placebo in improving symptoms compared to the baseline were determined using binomial logistic regression.p-value: 0.05Regression, Logistic
Primary
Symptom Severity
A combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity before and after drug vs. placebo intake. For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group.
Time frame: 40 min after drug or placebo administration
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) |
|---|---|---|---|
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Symptom Severity | Sodium oxybate | 28.0 score on a scale |
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Symptom Severity | Placebo | 14.2 score on a scale |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Symptom Severity | Sodium oxybate | 18.6 score on a scale |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Symptom Severity | Placebo | 12.3 score on a scale |
p-value: 0.01Mixed Models Analysis
Secondary
Length of Treatment Efficacy
The length of treatment efficacy in each EtOH+ and EtOH- group was assessed at 40, 180, and 300 min after drug vs. placebo intake compared to the baseline using a combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity. For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group.
Time frame: 40 min to 5 hours after drug or placebo administration
Population: Pre-specified to only report based on alcohol-responsiveness (EtOH+, EtOH-)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Length of Treatment Efficacy | Sodium oxybate: 40 min | 28.0 score on a scale | Standard Error 3.06 |
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Length of Treatment Efficacy | Sodium oxybate: 180 min | 18.63 score on a scale | Standard Error 3.36 |
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Length of Treatment Efficacy | Sodium oxybate: 300 min | 15.47 score on a scale | Standard Error 4.32 |
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Length of Treatment Efficacy | Placebo: 40 min | 14.23 score on a scale | Standard Error 3.71 |
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Length of Treatment Efficacy | Placebo: 180 min | 9.26 score on a scale | Standard Error 3.61 |
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Length of Treatment Efficacy | Placebo: 300 min | 10.30 score on a scale | Standard Error 3.15 |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Length of Treatment Efficacy | Placebo: 180 min | 9.31 score on a scale | Standard Error 1.99 |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Length of Treatment Efficacy | Sodium oxybate: 40 min | 18.60 score on a scale | Standard Error 2.31 |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Length of Treatment Efficacy | Placebo: 40 min | 12.34 score on a scale | Standard Error 1.39 |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Length of Treatment Efficacy | Sodium oxybate: 180 min | 12.67 score on a scale | Standard Error 2.4 |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Length of Treatment Efficacy | Placebo: 300 min | 8.16 score on a scale | Standard Error 1.84 |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Length of Treatment Efficacy | Sodium oxybate: 300 min | 8.33 score on a scale | Standard Error 1.98 |
p-value: 0.01ANOVA
Secondary
Relationship Between Alcohol-responsiveness of Symptoms and Drug-induced Symptom Improvement
A combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity before and 40 min after drug vs. placebo intake. For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group.
Time frame: 40 min after drug or placebo administration
Population: Pre-specified to only report based on alcohol-responsiveness (EtOH+, EtOH-)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Relationship Between Alcohol-responsiveness of Symptoms and Drug-induced Symptom Improvement | Sodium oxybate | 0.45 correlation coefficient |
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Relationship Between Alcohol-responsiveness of Symptoms and Drug-induced Symptom Improvement | Placebo | 0.06 correlation coefficient |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Relationship Between Alcohol-responsiveness of Symptoms and Drug-induced Symptom Improvement | Sodium oxybate | 0.09 correlation coefficient |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Relationship Between Alcohol-responsiveness of Symptoms and Drug-induced Symptom Improvement | Placebo | 0.22 correlation coefficient |
p-value: 0.01Pearson correlation
Secondary
Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics
A combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity before and 40 min after drug vs. placebo intake. For analysis, patients in groups (1) Alcohol-responsive (EtOH+) Laryngeal Dystonia and (2) Alcohol-responsive (EtOH+) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH+ group. For analysis, patients in groups (3) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia and (4) Alcohol-non-responsive (EtOH-) Laryngeal Dystonia with Dystonic Tremor of Voice were combined into the overall EtOH- group.
Time frame: 40 min after drug or placebo administration
Population: Pre-specified to only report based on alcohol-responsiveness (EtOH+, EtOH-)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics | Sodium oxybate: duration | -0.17 correlation coefficient |
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics | Placebo: duration | 0.18 correlation coefficient |
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics | Sodium oxybate: age of symptom onset | 0.16 correlation coefficient |
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics | Placebo: age of symptom onset | -0.18 correlation coefficient |
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics | Sodium oxybate: baseline symptom severity | -0.05 correlation coefficient |
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics | Placebo: baseline symptom severity | 0.24 correlation coefficient |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics | Sodium oxybate: baseline symptom severity | -0.04 correlation coefficient |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics | Sodium oxybate: duration | 0.10 correlation coefficient |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics | Placebo: age of symptom onset | -0.09 correlation coefficient |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics | Placebo: duration | 0.16 correlation coefficient |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics | Placebo: baseline symptom severity | -0.11 correlation coefficient |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Relationship Between Symptom Severity Change and Dystonia Clinical Characteristics | Sodium oxybate: age of symptom onset | -0.15 correlation coefficient |
p-value: 0.01Pearson correlation
Secondary
Treatment Efficacy Dependent on LD Clinical Type
A combined clinician-objective and patient-subjective change in visual analog scale (min-max 0-100, a higher score is the worse outcome) score of symptom severity before and after drug vs. placebo intake. EtOH+ and EtOH- were stratified based on phenotypical characteristics, including LD, LD with Dystonic Tremor of Voice, Abductor LD, Adductor LD.
Time frame: 40 min after drug or placebo administration
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Treatment Efficacy Dependent on LD Clinical Type | Placebo | 18.07 score on a scale | Standard Error 3.99 |
| Alcohol-responsive (EtOH+) Laryngeal Dystonia | Treatment Efficacy Dependent on LD Clinical Type | Sodium oxybate | 24.65 score on a scale | Standard Error 4.45 |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Treatment Efficacy Dependent on LD Clinical Type | Placebo | 10.85 score on a scale | Standard Error 5.9 |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Treatment Efficacy Dependent on LD Clinical Type | Sodium oxybate | 30.54 score on a scale | Standard Error 4.29 |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Treatment Efficacy Dependent on LD Clinical Type | Placebo | 10.34 score on a scale | Standard Error 1.94 |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia | Treatment Efficacy Dependent on LD Clinical Type | Sodium oxybate | 18.30 score on a scale | Standard Error 3.07 |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia With Dystonic Tremor of Voice | Treatment Efficacy Dependent on LD Clinical Type | Placebo | 14.47 score on a scale | Standard Error 1.93 |
| Alcohol-non-responsive (EtOH-) Laryngeal Dystonia With Dystonic Tremor of Voice | Treatment Efficacy Dependent on LD Clinical Type | Sodium oxybate | 18.96 score on a scale | Standard Error 3.49 |
| Alcohol-responsive Adductor Type of Laryngeal Dystonia | Treatment Efficacy Dependent on LD Clinical Type | Placebo | 13.59 score on a scale | Standard Error 6.07 |
| Alcohol-responsive Adductor Type of Laryngeal Dystonia | Treatment Efficacy Dependent on LD Clinical Type | Sodium oxybate | 31.70 score on a scale | Standard Error 5.08 |
| Alcohol-responsive Abductor Type of Laryngeal Dystonia | Treatment Efficacy Dependent on LD Clinical Type | Sodium oxybate | 24.85 score on a scale | Standard Error 3.92 |
| Alcohol-responsive Abductor Type of Laryngeal Dystonia | Treatment Efficacy Dependent on LD Clinical Type | Placebo | 13.10 score on a scale | Standard Error 4.62 |
| Alcohol-non-responsive Adductor Type of Laryngeal Dystonia | Treatment Efficacy Dependent on LD Clinical Type | Sodium oxybate | 21.36 score on a scale | Standard Error 2.86 |
| Alcohol-non-responsive Adductor Type of Laryngeal Dystonia | Treatment Efficacy Dependent on LD Clinical Type | Placebo | 13.07 score on a scale | Standard Error 1.54 |
| Alcohol-non-responsive Abductor Type of Laryngeal Dystonia | Treatment Efficacy Dependent on LD Clinical Type | Placebo | 11.32 score on a scale | Standard Error 2.83 |
| Alcohol-non-responsive Abductor Type of Laryngeal Dystonia | Treatment Efficacy Dependent on LD Clinical Type | Sodium oxybate | 14.96 score on a scale | Standard Error 4.04 |
p-value: 0.01t-test, 2 sided