Propranolol and Botulinum Toxin for Essential Vocal Tremor

NCT02111369 | Completed Phase 4 Results DMC

• 1 other identifier: IRB00072929
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Keywords

Essential Tremor; Essential Vocal Tremor; Essential Voice Tremor

Outcome Measures

Primary Outcomes (5)

• 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.

  Baseline, 2 weeks, 6 weeks

• 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.

  Baseline, 2 weeks, 6 weeks

• 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.

  Baseline, 2 weeks, 6 weeks

• Change in Global Voice Rating

  Patient-Reported Measure • 0-7 ranking

  Baseline, 2 weeks, 6 weeks

• 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

Study Arms (1)

Propranolol/Botulinum

EXPERIMENTAL

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; Procedure: Botulinum Toxin

Interventions

Propranolol 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.

Also known as: Inderal

Propranolol/Botulinum

Botulinum Toxin 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.

Propranolol/Botulinum

Eligibility Criteria

• Age: 45 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Emory University: lead

Study Sites (1)

Emory Voice Center

Atlanta, Georgia, 30308, United States

Location

Related Publications (6)

• 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.

  PMID: 20066728 BACKGROUND

• 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.

  PMID: 23881742 BACKGROUND

• 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.

  PMID: 23553653 BACKGROUND

• 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.

  PMID: 15364688 BACKGROUND

• 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.

  PMID: 10622521 BACKGROUND

• 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.

  PMID: 16103000 BACKGROUND

MeSH Terms

Conditions

Essential Tremor

Interventions

Propranolol; Botulinum Toxins

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Polycyclic Compounds; Metalloendopeptidases; Endopeptidases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Metalloproteases; Bacterial Proteins; Proteins; Amino Acids, Peptides, and Proteins; Bacterial Toxins; Toxins, Biological; Biological Factors

Limitations and Caveats

The study lacks a placebo or control group, with participants representing their own internal controls. Additionally, inter-rater reliability among listeners for the CAPE-V outcome measure analysis was low.

Results Point of Contact

• Title: Dr. Michael Johns
• Organization: Emory University

323-865-9839

Study Officials

• Michael Johns, MD

  Emory Voice Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Emory Voice Center

Study Record Dates

• First Submitted: April 8, 2014
• First Posted: April 11, 2014
• Study Start: May 1, 2014
• Primary Completion: October 1, 2014
• Study Completion: November 1, 2014
• Last Updated: April 27, 2016
• Results First Posted: April 27, 2016

Record last verified: 2016-03

Locations

US (1)