Effects of Octanoic Acid for Treatment of Essential Voice Tremor

• Sponsor: Syracuse University (Other)
• Overall Status: Completed
• CT.gov ID: NCT01864525
• Collaborator: National Institute on Deafness and Other Communication Disorders (NIDCD) (NIH)
• Enrollment: 17
• Location: 1
• Arms: 2
• Duration (Months): 45
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Essential Voice Tremor; Vocal Tremor; Voice Tremor; Essential Tremor of Voice	Drug: Octanoic acid; Drug: Inactive capsule	Phase 1/Phase 2

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

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Effects of Octanoic Acid for Treatment of Essential Voice Tremor
• Study Start Date: Jul 1, 2013
• Actual Primary Completion Date: Dec 22, 2016
• Actual Study Completion Date: Mar 31, 2017

Arms and Interventions

Arm	Intervention/Treatment
Placebo Comparator: Inactive capsule Participants will receive a pill/capsule with an inactive ingredient during the placebo arm of this study.	Drug: Inactive capsule; Other Names: Placebo
Experimental: Octanoic acid Participants will receive a pill/capsule with octanoic acid (amount determined by the participant's weight) during the experimental arm of this study.	Drug: Octanoic acid; Other Names: Caprylic acid

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Syracuse University & Upstate Medical University	Syracuse	New York	United States	13210

Sponsors and Collaborators

• Syracuse University
• National Institute on Deafness and Other Communication Disorders (NIDCD)

Investigators

• Principal Investigator: Soren Y Lowell, PhD, Syracuse University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Soren Lowell, Assistant Professor, Communication Sciences & Disorders, Syracuse University
• ClinicalTrials.gov Identifier: NCT01864525
• Other Study ID Numbers: 370955-3; 1R03DC012429-01A1
• First Posted: May 29, 2013
• Last Update Posted: Aug 20, 2018
• Last Verified: Jul 1, 2018

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Soren Lowell, Assistant Professor, Communication Sciences & Disorders, Syracuse University: voice; tremor; essential tremor; essential voice tremor; voice treatment; octanoic acid; octanol; voice disorder; dysphonia
• Additional relevant MeSH terms: Tremor; Essential Tremor

Study Results

Participant Flow

Arm/Group Title	Inactive Capsule First	Octanoic Acid First
Arm/Group Description	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	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
Period Title: Overall Study
STARTED	10	7
COMPLETED	9	7
NOT COMPLETED	1	0

Baseline Characteristics

Arm/Group Title	Inactive Capsule First	Octanoic Acid First	Total
Arm/Group Description	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	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	Total of all reporting groups
Overall Participants	10	7	17
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	68.90 (7.20)	70.43 (11.70)	69.53 (9.01)
Sex: Female, Male (Count of Participants)
Female	9 90%	6 85.7%	15 88.2%
Male	1 10%	1 14.3%	2 11.8%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	10 100%	7 100%	17 100%
Unknown or Not Reported	0 0%	0 0%	0 0%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	10 100%	7 100%	17 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%

Outcome Measures

1. Primary Outcome

Title	Magnitude of Acoustic Amplitude Tremor and Magnitude of Acoustic Frequency Tremor
Description	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)

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Octanoic Acid
Arm/Group Description	Participants who received a capsule with an inactive ingredient (placebo) during either the first or last 3 weeks of the study. Placebo	Participants who received a capsule with octanoic acid (amount determined by the participant's weight) during either the first or last 3 weeks of the study. Octanoic acid
Measure Participants	16	16
Baseline Magnitude of Acoustic Amplitude Tremor	12.91 (6.46)	13.49 (6.48)
Post-test Magnitude of Acoustic Amplitude Tremor	12.43 (7.37)	9.35 (5.42)
Baseline Magnitude of Acoustic Frequency Tremor	5.57 (4.29)	5.19 (3.58)
Post-test Magnitude of Acoustic Frequency Tremor	5.35 (3.76)	3.98 (2.94)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Octanoic Acid
	Comments	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).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0216
	Comments	Statistical results for Magnitude of acoustic amplitude tremor. A priori significance threshold was set at P<0.05 for each of the two hypothesis-driven acoustic variables.
	Method	Mixed Models Analysis
	Comments	This statistical test did not use the baseline scores as a covariate when comparing post-test scores between placebo and octanoic acid conditions.

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo, Octanoic Acid
	Comments	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).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0499
	Comments	Statistical results for Magnitude of acoustic amplitude tremor. A priori significance threshold was set at P<0.05 for each of the two hypothesis-driven acoustic variables.
	Method	Mixed Models Analysis
	Comments	This statistical test used the baseline scores as a covariate when comparing post-test scores between placebo and octanoic acid conditions.

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo, Octanoic Acid
	Comments	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).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0339
	Comments	Statistical results for Magnitude of acoustic frequency tremor. A priori significance threshold was set at P<0.05 for each of the two hypothesis-driven acoustic variables.
	Method	Mixed Models Analysis
	Comments	This statistical test did not use the baseline scores as a covariate when comparing post-test scores between placebo and octanoic acid conditions.

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo, Octanoic Acid
	Comments	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).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0450
	Comments	Statistical results for Magnitude of acoustic frequency tremor. A priori significance threshold was set at P<0.05 for each of the two hypothesis-driven acoustic variables.
	Method	Mixed Models Analysis
	Comments	This statistical test used the baseline scores as a covariate when comparing post-test scores between placebo and octanoic acid conditions.

2. Secondary Outcome

Title	Auditory-perceptual Tremor Severity Ratings
Description	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).

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Placebo	Octanoic Acid
Arm/Group Description	Participants who received a capsule with an inactive ingredient (placebo) during either the first or last 3 weeks of the study. Placebo	Participants who received a capsule with octanoic acid (amount determined by the participant's weight) during either the first or last 3 weeks of the study. Octanoic acid
Measure Participants	16	16
Sustained vowel, summed binary ratings (0-3)	1.25 (1.13)	1.53 (1.13)
Sentence-level, summed binary ratings (0-3)	1.63 (1.12)	1.19 (0.87)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo, Octanoic Acid
	Comments	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).
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7172
	Comments	A priori significance was set at P<0.05 for this hypothesis-driven auditory-perceptual variable. Main effect for drug is given above. For the main task effect, P=0.9602. For the interaction effect of drug*task, P=0.1699.
	Method	Mixed Models Analysis
	Comments

Adverse Events

Time Frame	For each participant, adverse event data were collected over approximately an 11 week period. This included data beginning with baseline testing in week 1, Phase 1 (placebo or octanoic acid condition) and continued through the week after post-test data was completed for Phase 2, on the final study visit (final nursing assessment visit).
Adverse Event Reporting Description	Participants completed symptom questionnaires with an independent nurse at four time-points: baseline before either the placebo or octanoic acid conditions, during the 3 weeks intake for each study phase, and upon completion of the study. Additionally, participants were called daily to inquire about any symptoms/symptom severity for three days after full drug intake was initiated for each study phase (placebo or octanoic acid) and then every 3-5 days thereafter each 3 week dosing period.
Arm/Group Title	Placebo		Octanoic Acid
Arm/Group Description	Study phase 1 or 2, when participants were randomized to the 3-week intervention phase in which an inactive capsule (placebo or inactive drug) was taken once a day for 3 weeks.		Study phase 1 or 2, when participants were randomized to the 3-week intervention phase in which octanoic acid (the active drug) was taken once a day for 3 weeks.
All Cause Mortality
	Placebo		Octanoic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)
Serious Adverse Events
	Placebo		Octanoic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/17 (0%)		0/17 (0%)
Other (Not Including Serious) Adverse Events
	Placebo		Octanoic Acid
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/17 (5.9%)		0/17 (0%)
Gastrointestinal disorders
Diarrhea	1/17 (5.9%)	1	0/17 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.