Propranolol and Botulinum Toxin for Essential Vocal Tremor

NCT ID: NCT02111369

Last Updated: 2016-04-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 18 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2014-05-31
• Study Completion Date: 2014-11-30

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.

Conditions

Essential Vocal Tremor; Essential Voice Tremor; Essential Tremor; Voice Tremor; Vocal Tremor

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Propranolol

Intervention Type: DRUG

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.

Botulinum Toxin

Intervention Type: PROCEDURE

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

Other Intervention Names

Inderal

Eligibility Criteria

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.

• Minimum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Emory University

OTHER

Sponsor Role: lead

Responsible Party

Michael M Johns MD

Director, Emory Voice Center

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Michael Johns, MD

Role: PRINCIPAL_INVESTIGATOR

Emory Voice Center

Locations

Emory Voice Center

Atlanta, Georgia, United States

Countries

United States

References

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.

Reference Type: BACKGROUND

PMID: 20066728 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23881742 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 23553653 (View on PubMed)

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. doi: 10.1001/archneur.61.9.1416.

Reference Type: BACKGROUND

PMID: 15364688 (View on PubMed)

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. doi: 10.1016/s0892-1997(99)80010-1.

Reference Type: BACKGROUND

PMID: 10622521 (View on PubMed)

Troster 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. doi: 10.1016/j.parkreldis.2005.05.009.

Reference Type: BACKGROUND

PMID: 16103000 (View on PubMed)

Other Identifiers

IRB00072929

Identifier Type: -

Identifier Source: org_study_id