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

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

Status

Completed

Phases

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT02711995

Enrollment

Registered

2016-03-17

Start date

2015-12-15

Completion date

2016-09-29

Last updated

2018-02-05

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Essential Tremor

Keywords

botulinum toxin, injection augmentation, essential voice tremor

Brief summary

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

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.

Interventions

DRUGRenuGel

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.

DRUGBotulinum Toxin

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.

Study design

Allocation

NON_RANDOMIZED

Intervention model

CROSSOVER

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to 100 Years

Healthy volunteers

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

Design outcomes

Primary

Measure	Time frame	Description
Vocal Tremor Scoring System (VTSS)	Baseline and 30 days after intervention	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.

Secondary

Measure	Time frame	Description
Aerodynamic Data- Airflow	Baseline and 30 days after intervention	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.
Consensus Auditory-Perceptual Evaluation of Voice (CAPE-V)	Baseline and 30 days after intervention	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.
Voice Handicap Index-10 (VHI-10)	Baseline and 30 days after intervention	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.
Acoustic Analysis- Frequencies	Baseline and 30 days after intervention	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).
Aerodynamic Data- Peak Air Pressure	Baseline and 30 days after intervention	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.
Aerodynamic Data- Loudness	Baseline and 30 days after intervention	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.
Aerodynamic Data- Maximum Phonation Time	Baseline and 30 days after intervention	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.
Percent of Normal Function (PNF)	Baseline and 30 days after intervention	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.

Countries

United States

Participant flow

Recruitment details

Eight patients were enrolled in the study, and seven patients completed the study. The first participant enrolled on December 15, 2015 and the last patient completed the study on September 29, 2016. All patients were seen at Weill Cornell Medicine ENT located at 1305 York Avenue,5th Floor NY NY 10021

Pre-assignment details

One patient was excluded prior to the second intervention. Her neurologist started her on a medication that could have confounded our findings, therefore her participation in the study ended. She still received treatment, but was no longer considered a study subject.

Participants by arm

Arm	Count
Botulinum Toxin First and RenuGel After Patients with essential voice tremor underwent botulinum toxin chemodenervation injection. After washout (90 days) , patients underwent injection augmentation. 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.	7
Total	7

Arm

Count

Botulinum Toxin First and RenuGel After

Patients with essential voice tremor underwent botulinum toxin chemodenervation injection. After washout (90 days) , patients underwent injection augmentation. 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.

Total

Withdrawals & dropouts

Period	Reason	FG000
Washout (90 Days)	Conflicting medication	1

Baseline characteristics

Characteristic	Botulinum Toxin First and RenuGel After
Age, Categorical <=18 years	0 Participants
Age, Categorical >=65 years	4 Participants
Age, Categorical Between 18 and 65 years	3 Participants
Age, Continuous	62 years
Region of Enrollment United States	7 Participants
Sex: Female, Male Female	5 Participants
Sex: Female, Male Male	2 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 7	0 / 7
other Total, other adverse events	0 / 7	0 / 7
serious Total, serious adverse events	0 / 7	0 / 7

Outcome results

Primary

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.