Essential Tremor, Essential Vocal Tremor, Essential Voice Tremor, Vocal Tremor, Voice Tremor
Conditions
Keywords
Essential Tremor, Essential Vocal Tremor, Essential Voice Tremor
Brief summary
Essential tremor is the most common adult-onset movement disorder, and essential voice tremor is the vocal manifestation of essential tremor. While nearly all essential tremor patients experience hand tremor, many also manifest head tremor and voice tremor. Essential voice tremor can lead to increased vocal effort, decreased intelligibility, and misconstrued emotional state. Only one medication, propranolol, is FDA-approved to treat essential tremor. Propranolol is not felt to be nearly as effective for axial tremors (head, trunk, neck) as it is for extremity tremors. However, this has not been studied with any objective assessment in a prospective way for EVT. For patients with essential voice tremor, the limited published data suggests that botulinum toxin has been shown to lead to functional voice improvement. Botulinum toxin, though also not well-studied with objective voice outcomes, is a commonly used clinical therapy for treatment of essential voice tremor. While it is used more often for essential voice tremor than propranolol therapy, botulinum toxin also has not been prospectively studied with validated, objective voice outcome measures. The investigators would like to determine if propranolol has any significant effect on vocal tremor. The investigators would also like to determine, in an objective way, the effect of botulinum toxin on vocal tremor. If effective, propranolol would provide an affordable and non-invasive alternative or addition to botulinum toxin injections for patients with essential voice tremor.
Detailed description
Specific Aims • Determine the effect of propranolol on vocal tremor in the treatment-seeking population. To date, the nonselective beta-blocker propranolol remains the only agent approved for the treatment of essential tremor (ET). For ET, immediate and sustained release formations of propranolol are equally effective, while other beta-blockers like nadolol and timolol are not as effective. While propranolol improves tremor in greater than half of patients with essential tremor, its effects on tremor are not evenly distributed. Improvement in tremor symptoms is greater for limb tremor than axial tremor, and therefore propranolol is not commonly used for the treatment of essential voice tremor (EVT). However, its effect on essential voice tremor has never been objectively, prospectively studied. Our aim is to objectively determine the effect of propranolol on essential voice tremor in the treatment-seeking population by evaluating patients with EVT before and after propranolol therapy. • Determine the effect of botulinum toxin injections on vocal tremor in the treatment-seeking population. More recently, botulinum toxin A has been used for the treatment of EVT. Chemical denervation with botulinum toxin is only modestly effective in reducing limb tremor in ET and complicated by side effects of weakness. However, botulinum toxin seems to be more effective in treating EVT than other manifestations of ET. While prior studies have not enlisted validated assessments of voice quality to measure the effect of botulinum toxin injections on EVT, they have shown subjective improvement in acoustic measures of tremor and ratings of videotaped speech after therapy with botulinum toxin. Our aim is to objectively determine the effect of botulinum toxin on vocal tremor in the treatment-seeking population by evaluating patients with EVT before and after botulinum therapy. Voice Evaluations and Medications For the first evaluation, a research coordinator will collect demographics and patient reported data. This data will result from providing patient questionnaires and recording the patient's voice. VRQOL data will be collected by having the patient answer ten statements on a 1-5 scale, such as I have trouble speaking loudly or being heard in noisy situations or I run out of air and need to take frequent breaths. QUEST data will be also recorded to a 30-item essential tremor-specific questionnaire. Patient will also complete a global voice rating of a 0-7 scoring of How would you rate your voice today? After these subjective questionnaires, patient will participate in a vocal recording using prompts and passages from the validated CAPE-V voice assessment tool. After a discussion of the risks and benefits of propranolol therapy, the patient will then be given a prescription by the principal investigator for propranolol. The second evaluation will occur at an office visit two weeks after initiating propranolol therapy. Again, this will consist of patient-reported V-RQOL, QUEST, and global voice rating data. Patient will participate in a second vocal recording using prompts and passages from the validated CAPE-V voice assessment tool. At this second evaluation, patient will receive botulinum toxin injections. The risks and benefits of botulinum toxin therapy will be explained to the patient, and bilateral injections will take place. Four weeks after botulinum toxin injection, the patient will undergo the third voice assessment. Again, this will consist of patient-reported V-RQOL, QUEST, and global voice rating data. Patient will participate in a third vocal recording using prompts and passages from the validated CAPE-V voice assessment tool.
Interventions
DRUGPropranolol
After a discussion of the risks and benefits of propranolol therapy, the patient will then be given a prescription by the principal investigator for propranolol. This prescription will consist of a starting dose of generic immediate-release at 10 mg three times daily (30 mg each day) with an increase in dose in 5-7 days if there is no effect (60 mg each day) and if the patient had demonstrated no side effects. Dose may be increased to 240 mg each day depending on patient improvement and side effect profile.
PROCEDUREBotulinum Toxin
At the second evaluation, patient will receive botulinum toxin injections. The risks and benefits of botulinum toxin therapy will be explained to the patient, and bilateral injections will take place.
Sponsors
Emory University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of essential voice tremor * Patients who have received or are planning to receive botulinum toxin injections for essential voice tremor * Patients who give informed consent to be contacted for research
Exclusion criteria
* Patients who are already on a beta blocker * Patients who suffer from hypotension, bradycardia, or otherwise have a medical contraindication to beta blocker therapy (eg. moderate to severe bronchial asthma) If the patient has received botulinum toxin injections for EVT previously, a three-month washout period is necessary before participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Quality of Life in Essential Tremor (QUEST) Questionnaire Score | Baseline, 2 weeks, 6 weeks | The QUEST questionnaire is a 30 item self-reported essential tremor-specific quality of life scale that asks participants to rate responses (never/no, rarely, sometimes, frequently, always/yes, or not applicable). Total scores range between 0 to 100 where 0 is the best score and 100 is the worst score. A higher score indicates a lower quality of life. |
| Change in Voice-Related Quality Of Life (VRQOL) Questionnaire Score | Baseline, 2 weeks, 6 weeks | The VRQOL is a ten question self-reported measure that asks patients to rate responses from 1-5 (1=none, not a problem, 2=a small amount, 3=a moderate (medium) amount, 4=a lot, 5=problem is as bad as it can be). Total scores range from 0 to 100. A higher score indicates more problems interfering with day to day activities. |
| Change in Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) Score | Baseline, 2 weeks, 6 weeks | The CAPE-V is a clinically validated perceptual voice assessment tool that is used to describe the severity of auditory-perceptual attributes of a voice problem, in a way that can be communicated among clinicians. Participant's speech is recorded and evaluated by trained listeners. Listeners indicate overall tremor severity by making a tick mark on a 1 to 100 mm visual analog scale. Total scores range from 0 to 100 where 0 is the best score and 100 is the worst score. |
| Change in Global Voice Rating | Baseline, 2 weeks, 6 weeks | Patient-Reported Measure • 0-7 ranking |
| Change in Acoustic Spectrograms | baseline, 2 weeks, 6 weeks | Objective Voice Assessment • Using the Computerized Speech Laboratory speech and voice analysis system (KayPENTAX, Montvale, NJ) |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from the Emory Voice Center from August 2014 to February 2015.
Pre-assignment details
Participants who previously received botulinum toxin injections for essential voice tremor (EVT) underwent a three month washout period prior to participation.
Participants by arm
| Arm | Count |
|---|---|
| Propranolol/Botulinum After baseline analysis, participants were given a prescription by the principal investigator for propranolol. This prescription consisted of a starting dose of generic immediate-release at 10 mg three times per day (30 mg each day) with an increase in dose in 5-7 days if there is no effect (60 mg each day) and if the participant demonstrated no side effects. Dose was increased up to 240 mg a day depending on participant improvement and side effect profile. After second evaluation, participants received botulinum toxin injections. The risks and benefits of botulinum toxin therapy were explained to the participant, and bilateral injections took place. | 18 |
| Total | 18 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Lost to Follow-up | 2 |
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | Propranolol/Botulinum |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 14 Participants |
| Age, Categorical Between 18 and 65 years | 4 Participants |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 18 |
| serious Total, serious adverse events | 0 / 18 |
Outcome results
Primary
Change in Acoustic Spectrograms
Objective Voice Assessment • Using the Computerized Speech Laboratory speech and voice analysis system (KayPENTAX, Montvale, NJ)
Time frame: baseline, 2 weeks, 6 weeks
Population: Data were not collected as investigators found the Voice Related Quality of Life (VRQOL) scale to be a better measure.
Primary
Change in Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) Score
The CAPE-V is a clinically validated perceptual voice assessment tool that is used to describe the severity of auditory-perceptual attributes of a voice problem, in a way that can be communicated among clinicians. Participant's speech is recorded and evaluated by trained listeners. Listeners indicate overall tremor severity by making a tick mark on a 1 to 100 mm visual analog scale. Total scores range from 0 to 100 where 0 is the best score and 100 is the worst score.
Time frame: Baseline, 2 weeks, 6 weeks
Population: Participants who completed all three study visits (Baseline Visit 1, Visit 2, and Visit 3).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Propranolol/Botulinum | Change in Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) Score | Baseline (Visit 1) | 43.61 units on a scale | Standard Deviation 23.26 |
| Propranolol/Botulinum | Change in Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) Score | Visit 2 | 45.89 units on a scale | Standard Deviation 24.57 |
| Propranolol/Botulinum | Change in Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) Score | Visit 3 | 35.67 units on a scale | Standard Deviation 22.14 |
Primary
Change in Global Voice Rating
Patient-Reported Measure • 0-7 ranking
Time frame: Baseline, 2 weeks, 6 weeks
Population: Data were not collected as investigators found the Voice Related Quality of Life (VRQOL) scale to be a better measure.
Primary
Change in Quality of Life in Essential Tremor (QUEST) Questionnaire Score
The QUEST questionnaire is a 30 item self-reported essential tremor-specific quality of life scale that asks participants to rate responses (never/no, rarely, sometimes, frequently, always/yes, or not applicable). Total scores range between 0 to 100 where 0 is the best score and 100 is the worst score. A higher score indicates a lower quality of life.
Time frame: Baseline, 2 weeks, 6 weeks
Population: Participants who completed all three study visits (Baseline Visit 1, Visit 2, and Visit 3).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Propranolol/Botulinum | Change in Quality of Life in Essential Tremor (QUEST) Questionnaire Score | Baseline (Visit 1) | 39.41 units on a scale | Standard Deviation 27.89 |
| Propranolol/Botulinum | Change in Quality of Life in Essential Tremor (QUEST) Questionnaire Score | Visit 2 | 29.50 units on a scale | Standard Deviation 23.73 |
| Propranolol/Botulinum | Change in Quality of Life in Essential Tremor (QUEST) Questionnaire Score | Visit 3 | 23.60 units on a scale | Standard Deviation 24.49 |
Primary
Change in Voice-Related Quality Of Life (VRQOL) Questionnaire Score
The VRQOL is a ten question self-reported measure that asks patients to rate responses from 1-5 (1=none, not a problem, 2=a small amount, 3=a moderate (medium) amount, 4=a lot, 5=problem is as bad as it can be). Total scores range from 0 to 100. A higher score indicates more problems interfering with day to day activities.
Time frame: Baseline, 2 weeks, 6 weeks
Population: Participants who completed all three study visits (Baseline Visit 1, Visit 2, and Visit 3).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Propranolol/Botulinum | Change in Voice-Related Quality Of Life (VRQOL) Questionnaire Score | Baseline (Visit 1) | 42.22 units on a scale | Standard Deviation 23.64 |
| Propranolol/Botulinum | Change in Voice-Related Quality Of Life (VRQOL) Questionnaire Score | Visit 2 | 51.53 units on a scale | Standard Deviation 26.21 |
| Propranolol/Botulinum | Change in Voice-Related Quality Of Life (VRQOL) Questionnaire Score | Visit 3 | 64.16 units on a scale | Standard Deviation 22.23 |