Propranolol and Botulinum Toxin for Essential Vocal Tremor

March 25, 2016 updated by: Michael M Johns MD, Emory University
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

18

Phase

  • Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Georgia
      • Atlanta, Georgia, United States, 30308
        • Emory Voice Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

45 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Propranolol/Botulinum
After baseline analysis, patient will 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 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 patient had demonstrated no side effects. Dose may be increased to 240 mg each day depending on patient improvement and side effect profile. After 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.
Drug: Propranolol
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.
Other Names:
  • Inderal
Procedure: Botulinum 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Change in Quality of Life in Essential Tremor (QUEST) Questionnaire Score
Time Frame: 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.
Baseline, 2 weeks, 6 weeks
Change in Voice-Related Quality Of Life (VRQOL) Questionnaire Score
Time Frame: 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.
Baseline, 2 weeks, 6 weeks
Change in Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) Score
Time Frame: 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.
Baseline, 2 weeks, 6 weeks
Change in Global Voice Rating
Time Frame: Baseline, 2 weeks, 6 weeks

Patient-Reported Measure

• 0-7 ranking
Baseline, 2 weeks, 6 weeks
Change in Acoustic Spectrograms
Time Frame: baseline, 2 weeks, 6 weeks

Objective Voice Assessment

• Using the Computerized Speech Laboratory speech and voice analysis system (KayPENTAX, Montvale, NJ)
baseline, 2 weeks, 6 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Emory University

Investigators

  • Principal Investigator: Michael Johns, MD, Emory Voice Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2014

Primary Completion (Actual)

October 1, 2014

Study Completion (Actual)

November 1, 2014

Study Registration Dates

First Submitted

April 8, 2014

First Submitted That Met QC Criteria

April 10, 2014

First Posted (Estimate)

April 11, 2014

Study Record Updates

Last Update Posted (Estimate)

April 27, 2016

Last Update Submitted That Met QC Criteria

March 25, 2016

Last Verified

March 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IRB00072929

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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