Propranolol and Botulinum Toxin for Essential Vocal Tremor

Essential Tremor Clinical Trial

Official title:

Propranolol and Botulinum Toxin for Essential Vocal Tremor

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02111369
• Other study ID #: IRB00072929
• Status: Completed
• Phase: Phase 4
• First received: April 8, 2014
• Last updated: May 8, 2015
• Start date: May 2014
• Est. completion date: November 2014

Study information

• Verified date: May 2015
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: November 2014
• Est. primary completion date: October 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 45 Years and older

Eligibility

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 Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Essential Tremor
• Essential Vocal Tremor
• Essential Voice Tremor
• Tremor
• Vocal Tremor
• Voice Tremor

Intervention

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.

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.

Locations

Country	Name	City	State
United States	Emory Voice Center	Atlanta	Georgia

Sponsors (1)

Lead Sponsor	Collaborator
Emory University

Country where clinical trial is conducted

United States, 

References & Publications (6)

Adler CH, Bansberg SF, Hentz JG, Ramig LO, Buder EH, Witt K, Edwards BW, Krein-Jones K, Caviness JN. Botulinum toxin type A for treating voice tremor. Arch Neurol. 2004 Sep;61(9):1416-20. — View Citation

Gurey LE, Sinclair CF, Blitzer A. A new paradigm for the management of essential vocal tremor with botulinum toxin. Laryngoscope. 2013 Oct;123(10):2497-501. doi: 10.1002/lary.24073. Epub 2013 Apr 1. — View Citation

Hogikyan ND, Sethuraman G. Validation of an instrument to measure voice-related quality of life (V-RQOL). J Voice. 1999 Dec;13(4):557-69. — View Citation

Sulica L, Louis ED. Clinical characteristics of essential voice tremor: a study of 34 cases. Laryngoscope. 2010 Mar;120(3):516-28. doi: 10.1002/lary.20702. — View Citation

Tröster AI, Pahwa R, Fields JA, Tanner CM, Lyons KE. Quality of life in Essential Tremor Questionnaire (QUEST): development and initial validation. Parkinsonism Relat Disord. 2005 Sep;11(6):367-73. — View Citation

Zesiewicz TA, Shaw JD, Allison KG, Staffetti JS, Okun MS, Sullivan KL. Update on treatment of essential tremor. Curr Treat Options Neurol. 2013 Aug;15(4):410-23. doi: 10.1007/s11940-013-0239-4. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Voice-Related Quality Of Life (VRQOL) questionnaire	Patient-Reported Measure; • 10 questions for patient to score 1-5; 10-50 raw score	baseline, 2 weeks, 6 weeks	No
Primary	Change in Quality of Life in Essential Tremor (QUEST) questionnaire	Patient-Reported Measure; • 30-item, Essential Tremor-specific quality of life scale	baseline, 2 weeks, 6 weeks	No
Primary	Change in Global voice rating	Patient-Reported Measure; • 0-7 ranking	baseline, 2 weeks, 6 weeks	No
Primary	Change in Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) tool	Objective Voice Assessment; • Sustained vowel, sentences, running speech; 0-100 scale	baseline, 2 weeks, 6 weeks	No
Primary	Change in Acoustic Spectrograms	Objective Voice Assessment; • Using the Computerized Speech Laboratory speech and voice analysis system (KayPENTAX, Montvale, NJ)	baseline, 2 weeks, 6 weeks	No