Essential Tremor of Voice, Essential Voice Tremor, Vocal Tremor, Voice Tremor
Conditions
Keywords
voice, tremor, essential tremor, essential voice tremor, voice treatment, octanoic acid, octanol, voice disorder, dysphonia
Brief summary
Essential voice tremor is a neurological condition that produces a regular, shaking quality in the voice. One form of drug treatment that produces some improvement in tremor of the hands is octanoic acid, which is a food additive that is similar to alcohol. Research suggests that octanoic acid may reduce tremor in the hands/arms with few side effects and no intoxication effects. This study will determine whether octanoic acid may be useful for reducing tremor when it affects the voice. Researchers are hypothesizing that octanoic acid will reduce the effects of tremor on the voice.
Detailed description
Background: * Essential tremor of the voice produces regular shaking and hoarseness in the voice, making it difficult speech difficult to understand * Several previous studies have found that octanoic acid and octanol, which are related to alcohol, can improve tremor in some people without producing many side effects and without producing intoxication * Researchers are interested in determining whether octanoic acid can improve tremor that affects the voice Objectives: * To determine the effects of octanoic voice using voice recordings and listener ratings of voice * To determine the effects of octanoic acid on level of voice disability experienced by people with essential voice tremor
Interventions
DRUGOctanoic acid
DRUGInactive capsule
Sponsors
National Institute on Deafness and Other Communication Disorders (NIDCD)
Syracuse University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants have a diagnosis of essential voice tremor and show signs of tremor during the endoscopy examination (when pictures of the voice box are obtained)during screening appointment * Participants show measurable voice tremor from recordings of the voice during screening appointment
Exclusion criteria
* Participants have a diagnosis or show signs of Parkinson's Disease or another non-essential tremor movement disorder * Participants have a diagnosis or show signs of spasmodic dysphonia (a different neurological voice disorder) * Participants have a diagnosis of a severe, non-stable medical condition, such as kidney or liver failure, severe heart disease, severe lung disease, severe metabolic disease, uncontrolled hyperthyroidism, or other life-threatening disease such as active cancer * Participants have a diagnosis of diabetes mellitus * Participants are unable to suspend/stop a medication that they are currently taking for tremor or voice disorder for 12 weeks to complete this study * Participants have a dependence on alcohol or allergy to alcohol * Participants are pregnant or lactating * Participants have an allergy to soy * Participants have Irritable Bowel Syndrome
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Magnitude of Acoustic Amplitude Tremor and Magnitude of Acoustic Frequency Tremor | Measured at baseline visits (1 & 2) and after 3 weeks of placebo or octanoic acid on post-test visits (1 & 2) | Voice recordings were used to measure the degree of tremor in the voice. Mean post-test values for each acoustic measure were compared after the octanoic acid and placebo conditions, with and without consideration of baseline values. Mean values represent the average of two testing days. Degree of amplitude tremor shows the extent of amplitude variation as a percent of the mean signal amplitude, with lower numbers indicating less amplitude tremor. Baseline values for magnitude of amplitude tremor across all participants and conditions ranged from 4.06 to 27.09, and post-test values ranged from 1.94 to 26.02. Degree of frequency tremor shows the extent of fundamental frequency variation as a percent of the mean signal frequency, with lower numbers indicating less frequency tremor. Baseline values for magnitude of frequency tremor across all participants and conditions ranged from 1.21 to 15.31, and post-test values ranged from 0.60 to 13.86. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Auditory-perceptual Tremor Severity Ratings | Measured at baseline visits (1 & 2) and after 3 weeks of placebo or octanoic acid on post-test visits (1 & 2). | Three experienced listeners independently rated each participant's voice from paired sample recordings comparing the baseline to post-test samples in randomized order for each condition. Sustained vowel and sentence-level recordings were rated, with decoded samples later analyzed for 1=better for post-test compared to baseline, 0= no difference between post-test and baseline. Maximum score for each participant was 3 (post-test was better for each of three raters). The range of possible scores was the sum of each of three raters' scores (0 to 3), with 0 indicating no difference between baseline and post-test voice tremor severity rating, and 3 indicating better voice (less tremor severity) at post-testing compared to pre-testing. Mean post-test values for task were compared for the octanoic acid and placebo conditions, and all raters were blind to which sample was a baseline versus a post-test recording, and which samples were associated with the \[placebo or octanoic acid conditions. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Inactive Capsule First Participants who were randomized to receive a capsule with an inactive ingredient (placebo) during the first 3 weeks of the study (placebo arm of crossover design study), and then received octanoic acid in the last 3 weeks of the study.
Placebo | 10 |
| Octanoic Acid First Participants who were randomized to receive a capsule with octanoic acid (amount determined by the participant's weight) during the first 3 weeks of the study (experimental arm of crossover design study), and then received the placebo in the last 3 weeks of the study.
Octanoic acid | 7 |
| Total | 17 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
Baseline characteristics
| Characteristic | Octanoic Acid First | Total | Inactive Capsule First |
|---|---|---|---|
| Age, Continuous | 70.43 years STANDARD_DEVIATION 11.7 | 69.53 years STANDARD_DEVIATION 9.01 | 68.90 years STANDARD_DEVIATION 7.2 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 7 Participants | 17 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 17 Participants | 10 Participants |
| Sex: Female, Male Female | 6 Participants | 15 Participants | 9 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 17 | 0 / 17 |
| other Total, other adverse events | 1 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Primary
Magnitude of Acoustic Amplitude Tremor and Magnitude of Acoustic Frequency Tremor
Voice recordings were used to measure the degree of tremor in the voice. Mean post-test values for each acoustic measure were compared after the octanoic acid and placebo conditions, with and without consideration of baseline values. Mean values represent the average of two testing days. Degree of amplitude tremor shows the extent of amplitude variation as a percent of the mean signal amplitude, with lower numbers indicating less amplitude tremor. Baseline values for magnitude of amplitude tremor across all participants and conditions ranged from 4.06 to 27.09, and post-test values ranged from 1.94 to 26.02. Degree of frequency tremor shows the extent of fundamental frequency variation as a percent of the mean signal frequency, with lower numbers indicating less frequency tremor. Baseline values for magnitude of frequency tremor across all participants and conditions ranged from 1.21 to 15.31, and post-test values ranged from 0.60 to 13.86.
Time frame: Measured at baseline visits (1 & 2) and after 3 weeks of placebo or octanoic acid on post-test visits (1 & 2)
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Magnitude of Acoustic Amplitude Tremor and Magnitude of Acoustic Frequency Tremor | Baseline Magnitude of Acoustic Amplitude Tremor | 12.91 percentage of voice signal with tremor | Standard Deviation 6.46 |
| Placebo | Magnitude of Acoustic Amplitude Tremor and Magnitude of Acoustic Frequency Tremor | Post-test Magnitude of Acoustic Amplitude Tremor | 12.43 percentage of voice signal with tremor | Standard Deviation 7.37 |
| Placebo | Magnitude of Acoustic Amplitude Tremor and Magnitude of Acoustic Frequency Tremor | Baseline Magnitude of Acoustic Frequency Tremor | 5.57 percentage of voice signal with tremor | Standard Deviation 4.29 |
| Placebo | Magnitude of Acoustic Amplitude Tremor and Magnitude of Acoustic Frequency Tremor | Post-test Magnitude of Acoustic Frequency Tremor | 5.35 percentage of voice signal with tremor | Standard Deviation 3.76 |
| Octanoic Acid | Magnitude of Acoustic Amplitude Tremor and Magnitude of Acoustic Frequency Tremor | Post-test Magnitude of Acoustic Frequency Tremor | 3.98 percentage of voice signal with tremor | Standard Deviation 2.94 |
| Octanoic Acid | Magnitude of Acoustic Amplitude Tremor and Magnitude of Acoustic Frequency Tremor | Baseline Magnitude of Acoustic Amplitude Tremor | 13.49 percentage of voice signal with tremor | Standard Deviation 6.48 |
| Octanoic Acid | Magnitude of Acoustic Amplitude Tremor and Magnitude of Acoustic Frequency Tremor | Baseline Magnitude of Acoustic Frequency Tremor | 5.19 percentage of voice signal with tremor | Standard Deviation 3.58 |
| Octanoic Acid | Magnitude of Acoustic Amplitude Tremor and Magnitude of Acoustic Frequency Tremor | Post-test Magnitude of Acoustic Amplitude Tremor | 9.35 percentage of voice signal with tremor | Standard Deviation 5.42 |
Comparison: Separate measures for magnitude of amplitude tremor and magnitude of frequency tremor were analyzed as these variables can respond differently to treatment and may be differentially affected in essential voice tremor. Statistical modeling tested for post-treatment drug differences, with testing session as a repeated factor. Models were run with and without inclusion of baseline averages as a covariate per recommendations for cross-over treatment studies (Fleiss, Wallenstein \& Rosenfeld, 1985).p-value: 0.0216Mixed Models Analysis
Comparison: Separate measures for magnitude of amplitude tremor and magnitude of frequency tremor were analyzed as these variables can respond differently to treatment and may be differentially affected in essential voice tremor. Statistical modeling tested for post-treatment drug differences, with testing session as a repeated factor. Models were run with and without inclusion of baseline averages as a covariate per recommendations for cross-over treatment studies (Fleiss, Wallenstein \& Rosenfeld, 1985).p-value: 0.0499Mixed Models Analysis
Comparison: Separate measures for magnitude of amplitude tremor and magnitude of frequency tremor were analyzed as these variables can respond differently to treatment and may be differentially affected in essential voice tremor. Statistical modeling tested for post-treatment drug differences, with testing session as a repeated factor. Models were run with and without inclusion of baseline averages as a covariate per recommendations for cross-over treatment studies (Fleiss, Wallenstein \& Rosenfeld, 1985).p-value: 0.0339Mixed Models Analysis
Comparison: Separate measures for magnitude of amplitude tremor and magnitude of frequency tremor were analyzed as these variables can respond differently to treatment and may be differentially affected in essential voice tremor. Statistical modeling tested for post-treatment drug differences, with testing session as a repeated factor. Models were run with and without inclusion of baseline averages as a covariate per recommendations for cross-over treatment studies (Fleiss, Wallenstein \& Rosenfeld, 1985).p-value: 0.045Mixed Models Analysis
Secondary
Auditory-perceptual Tremor Severity Ratings
Three experienced listeners independently rated each participant's voice from paired sample recordings comparing the baseline to post-test samples in randomized order for each condition. Sustained vowel and sentence-level recordings were rated, with decoded samples later analyzed for 1=better for post-test compared to baseline, 0= no difference between post-test and baseline. Maximum score for each participant was 3 (post-test was better for each of three raters). The range of possible scores was the sum of each of three raters' scores (0 to 3), with 0 indicating no difference between baseline and post-test voice tremor severity rating, and 3 indicating better voice (less tremor severity) at post-testing compared to pre-testing. Mean post-test values for task were compared for the octanoic acid and placebo conditions, and all raters were blind to which sample was a baseline versus a post-test recording, and which samples were associated with the \[placebo or octanoic acid conditions.
Time frame: Measured at baseline visits (1 & 2) and after 3 weeks of placebo or octanoic acid on post-test visits (1 & 2).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo | Auditory-perceptual Tremor Severity Ratings | Sustained vowel, summed binary ratings (0-3) | 1.25 units on a scale | Standard Deviation 1.13 |
| Placebo | Auditory-perceptual Tremor Severity Ratings | Sentence-level, summed binary ratings (0-3) | 1.63 units on a scale | Standard Deviation 1.12 |
| Octanoic Acid | Auditory-perceptual Tremor Severity Ratings | Sustained vowel, summed binary ratings (0-3) | 1.53 units on a scale | Standard Deviation 1.13 |
| Octanoic Acid | Auditory-perceptual Tremor Severity Ratings | Sentence-level, summed binary ratings (0-3) | 1.19 units on a scale | Standard Deviation 0.87 |
Comparison: Statistical modeling tested for main effects of auditory-perceptual ratings for drug and task (sustained vowel and sentence-level ratings), and interaction effects of these variables. The summed scores, averaged across all participants, are provided separately for the sustained vowel and sentence-level ratings. Values range from 0 (no difference between baseline and post-test) to 3 (all three raters indicated that post-test sample was better (less tremor severity).p-value: 0.7172Mixed Models Analysis