Essential Voice Tremor: A Study of Botulinum Toxin Treatment and Injection Augmentation

Study Overview
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Brief Summary
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Botulinum toxin is the common treatment of choice for patients with Essential Voice Tremor (EVT), but results are not universally beneficial to all patients. Inconsistent results are noted in the literature and are consistent with the PI's clinical experience. Injection augmentation, a well-established treatment for glottic insufficiency, which is a prominent factor in the clinical presentation of Essential Voice Tremor (EVT), has not been studied. By treating patients at separate times with botulinum toxin and injection augmentation in an unblinded prospective crossover treatment study, we can assess functional outcomes of these two treatments with the population of patients with Essential Voice Tremor (EVT).

Detailed Description
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The purpose of this study is to compare treatment with botulinum toxin to treatment with injection augmentation in patients diagnosed with essential voice tremor. Botulinum toxin treatment is the injection of botulinum toxin into the muscles of the vocal cords through the skin of the neck. This is identical to the injections you may have received in the past for your disorder. Injection augmentation is the injection of a filler material into the vocal cords through the skin of the neck, guided by the view from a flexible laryngoscope inserted through the nostril. The flexible laryngoscopy is identical to the procedure that the doctor has used to examine your vocal cords in the past. It is the routine diagnostic evaluation technique of voice disorders. Periodic injections with botulinum toxin (Botox) is the current standard of care for patients diagnosed with essential voice tremor, but studies show only about 60% of patients benefit substantially enough to continue treatment. Poor vocal fold closure, a common characteristic of essential voice tremor, is treated in other situations (such as vocal fold paralysis or paresis) with injection augmentation; thus there is reason to think that it may be helpful to patients with essential voice tremor, perhaps even to a greater extent than botulinum toxin.

Official Title
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Essential Voice Tremor: An Unblinded Crossover Study of Botulinum Toxin Treatment and Injection Augmentation

Conditions
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Essential Tremor

Intervention / Treatment
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* Drug: RenuGel
* Drug: Botulinum Toxin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients ages 18-100 who have been diagnosed with essential tremor of the voice (EVT) Diagnosis Code 478.75 Laryngeal Spasm. Exclusion Criteria: WCMC subjects under age 18 Pregnant patients Patients with laryngeal pathology besides tremor, including but not limited to polyps and other benign lesions, precancerous or cancerous changes, vocal fold paralysis, or other laryngeal disorders of mobility

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 100 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RenuGel<br>Injection augmentation is the injection of a filler material (Brand: RenuGel; generic: Carboxymethylcellulose) into the vocal cords through the skin of the neck, guided by the view from a flexible laryngoscope inserted through the nostril. The flexible laryngoscopy is identical to the procedure that the doctor has used to examine your vocal cords in the past. It is the routine diagnostic evaluation technique of voice disorders. | Drug: RenuGel<br>* Injection augmentation is the injection of a filler material (Brand: RenuGel; generic: Carboxymethylcellulose) into the vocal cords through the skin of the neck, guided by the view from a flexible laryngoscope inserted through the nostril. The flexible laryngoscopy is identical to the procedure that the doctor has used to examine your vocal cords in the past. It is the routine diagnostic evaluation technique of voice disorders.<br>* Other names: generic: Carboxymethylcellulose;|
| Active Comparator: Botulinum toxin<br>Botulinum toxin treatment is the injection of botulinum toxin into the muscles of the vocal cords through the skin of the neck. This is identical to the injections you may have received in the past for your disorder. | Drug: Botulinum Toxin<br>* Botulinum toxin treatment is the injection of botulinum toxin into the muscles of the vocal cords through the skin of the neck. This is identical to the injections you may have received in the past for your disorder.<br>* Other names: Botox;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vocal Tremor Scoring System (VTSS) | The Vocal Tremor Scoring System (VTSS) was developed to standardize the evaluation and scaling of vocal tremor. Tremor at a specific site was scored according to severity by the laryngologist. It can be rated as: none (0), mild/intermittent (1), moderate (2), severe (3). Six different regions were evaluated in this study: base of tongue, larynx, palate, pharyngeal walls, supraglottis, and true vocal folds. The scale range for each region was 0-3. The total score was a summation of all six regions, with a scalar range of 0-18. | Baseline and 30 days after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acoustic Analysis- Frequencies | For acoustic assessment, subjects produced a sustained /a/ sound at their habitual speaking pitch and loudness and read assessment sentences from the Consensus Audio-Perceptual Evaluation of Voice (CAPE-V)protocol. Tasks were recorded and analyzed using the Analysis of Dysphonia in Speech and Voice (ADSV) and Multi-Dimensional Voice Profile (MDVP) software. A handheld microphone 3 inches from the subjects' mouths was used for all recordings. The Sustained Vowel and All-Voiced Sentence protocols of the ADSV were used to obtain cepstral peak prominence fundamental frequency (CPP F0), The MDVP was used to obtain amplitude tremor frequency (Fatr), and fundamental frequency tremor frequency (Fftr). | Baseline and 30 days after intervention | 
| Aerodynamic Data- Airflow | Aerodynamic data were collected using the Phonatory Aerodynamic System (PAS) 6600 (Pentax). Subjects held a facemask coupled to a pneumotachometer with a pressure-sensor tube firmly over the nose and mouth, and rested the pressure-sensor tube in the oral cavity above the tongue. They produced sustained /a/ and We were away a year ago, from which mean airflow wasanalyzed via the Maximum Sustained Phonation and Running Speech protocols. | Baseline and 30 days after intervention | 
| Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) | The Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V) is used to describe the severity of auditory-perceptual attributes of a voice problem. It indicates salient perceptual vocal attributes: (a) Overall Severity; (b) Roughness; (c) Breathiness; (d) Strain; (e) Pitch; and (f) Loudness. The CAPE-V displays each attribute accompanied by a 100- millimeter line forming a visual analog scale (VAS). The clinician indicates the degree of perceived deviance from normal for each parameter on this scale, using a tic mark. For each dimension, scalar extremes are unlabeled. The scale range is from 0mm to 100mm. Results can indicate distance in mm to describe the degree of deviancy, so the higher the score the more deviancy from the norm there is. | Baseline and 30 days after intervention | 
| Voice Handicap Index-10 (VHI-10) | The Voice Handicap Index-10 consists of 10 questions (statements about voice), where patients rate their the frequency of their problems as: never (0), almost never (1), sometimes (2), almost always (3), and always (4). The scores from each answer are added, and can range from 0-40. The higher the score, the worse the patient's perception of their voice handicap. | Baseline and 30 days after intervention | 
| Percent of Normal Function (PNF) | The Percent of Normal Function (PNF) is a scale for patients to rate their recurrent functions in increments of five, from no function (0%) to normal function (100%). The higher the percentage, the more normal the function as experienced by the patient. | Baseline and 30 days after intervention | 
| Aerodynamic Data- Peak Air Pressure | Aerodynamic data were collected using the Phonatory Aerodynamic System (PAS) 6600 (Pentax). Subjects held a facemask coupled to a pneumotachometer with a pressure-sensor tube firmly over the nose and mouth, and rested the pressure-sensor tube in the oral cavity above the tongue. A string of five consonant-vowel syllables (/pa/) at a comfortable pitch and loudness were analyzed through the Voicing Efficiency protocol to determine mean peak air pressure. | Baseline and 30 days after intervention | 
| Aerodynamic Data- Loudness | Aerodynamic data were collected using the Phonatory Aerodynamic System (PAS) 6600 (Pentax). Subjects held a facemask coupled to a pneumotachometer with a pressure-sensor tube firmly over the nose and mouth, and rested the pressure-sensor tube in the oral cavity above the tongue. They produced sustained /a/ and We were away a year ago, from which loudness was analyzed via the Maximum Sustained Phonation and Running Speech protocols. | Baseline and 30 days after intervention | 
| Aerodynamic Data- Maximum Phonation Time | Aerodynamic data were collected using the Phonatory Aerodynamic System (PAS) 6600 (Pentax). Subjects held a facemask coupled to a pneumotachometer with a pressure-sensor tube firmly over the nose and mouth, and rested the pressure-sensor tube in the oral cavity above the tongue. They produced sustained /a/ from which Maximum Sustained Phonation time was recorded. | Baseline and 30 days after intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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botulinum toxin, injection augmentation, essential voice tremor