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| ID | Type | Description | Link |
|---|---|---|---|
| 1R03DC012429-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institute on Deafness and Other Communication Disorders (NIDCD) | NIH |
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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.
Background:
Objectives:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Inactive capsule | Placebo Comparator | Participants will receive a pill/capsule with an inactive ingredient during the placebo arm of this study. |
|
| Octanoic acid | Experimental | Participants will receive a pill/capsule with octanoic acid (amount determined by the participant's weight) during the experimental arm of this study. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Octanoic acid | Drug |
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| |
| Inactive capsule |
| Measure | Description | Time Frame |
|---|---|---|
| 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. | Measured at baseline visits (1 & 2) and after 3 weeks of placebo or octanoic acid on post-test visits (1 & 2) |
| Measure | Description | Time Frame |
|---|---|---|
| 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.](streamdown:incomplete-link) |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Soren Y Lowell, PhD | Syracuse University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Syracuse University & Upstate Medical University | Syracuse | New York | 13210 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23408867 | Result | Haubenberger D, McCrossin G, Lungu C, Considine E, Toro C, Nahab FB, Auh S, Buchwald P, Grimes GJ, Starling J, Potti G, Scheider L, Kalowitz D, Bowen D, Carnie A, Hallett M. Octanoic acid in alcohol-responsive essential tremor: a randomized controlled study. Neurology. 2013 Mar 5;80(10):933-40. doi: 10.1212/WNL.0b013e3182840c4f. Epub 2013 Feb 13. | |
| 21594724 | Result | Nahab FB, Wittevrongel L, Ippolito D, Toro C, Grimes GJ, Starling J, Potti G, Haubenberger D, Bowen D, Buchwald P, Dong C, Kalowitz D, Hallett M. An open-label, single-dose, crossover study of the pharmacokinetics and metabolism of two oral formulations of 1-octanol in patients with essential tremor. Neurotherapeutics. 2011 Oct;8(4):753-62. doi: 10.1007/s13311-011-0045-1. |
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| ID | Title | Description |
|---|---|---|
| FG000 | 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 |
| FG001 | 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 |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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| ID | Title | Description |
|---|---|---|
| BG000 | 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 |
| BG001 | Octanoic Acid First |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | Posted | Mean | Standard Deviation | percentage of voice signal with tremor | Measured at baseline visits (1 & 2) and after 3 weeks of placebo or octanoic acid on post-test visits (1 & 2) |
|
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).
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.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo | 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. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhea | Gastrointestinal disorders | Systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Soren Lowell | Syracuse University | 315-443-9648 | slowell@syr.edu |
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| ID | Term |
|---|---|
| D014202 | Tremor |
| D020329 | Essential Tremor |
| D014832 | Voice Disorders |
| D055154 | Dysphonia |
| ID | Term |
|---|---|
| D020820 | Dyskinesias |
| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
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| ID | Term |
|---|---|
| C031492 | octanoic acid |
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| Drug |
|
|
| Measured at baseline visits (1 & 2) and after 3 weeks of placebo or octanoic acid on post-test visits (1 & 2). |
| 22454323 | Result | Nahab FB, Handforth A, Brown T, Shin C, Quesada A, Dong C, Haubenberger D, Hallett M. Octanoic acid suppresses harmaline-induced tremor in mouse model of essential tremor. Neurotherapeutics. 2012 Jul;9(3):635-8. doi: 10.1007/s13311-012-0121-1. |
| 15210907 | Result | Shill HA, Bushara KO, Mari Z, Reich M, Hallett M. Open-label dose-escalation study of oral 1-octanol in patients with essential tremor. Neurology. 2004 Jun 22;62(12):2320-2. doi: 10.1212/wnl.62.12.2320. |
| 14718713 | Result | Bushara KO, Goldstein SR, Grimes GJ Jr, Burstein AH, Hallett M. Pilot trial of 1-octanol in essential tremor. Neurology. 2004 Jan 13;62(1):122-4. doi: 10.1212/01.wnl.0000101722.95137.19. |
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 |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Title |
|---|
| Description |
|---|
| OG000 | Placebo | Participants who received a capsule with an inactive ingredient (placebo) during either the first or last 3 weeks of the study. Placebo |
| OG001 | Octanoic Acid | 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 |
|
|
|
| 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.](streamdown:incomplete-link) | Posted | Mean | Standard Deviation | units on a scale | Measured at baseline visits (1 & 2) and after 3 weeks of placebo or octanoic acid on post-test visits (1 & 2). |
|
|
|
|
| 0 |
| 17 |
| 0 |
| 17 |
| 1 |
| 17 |
| EG001 | Octanoic Acid | 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. | 0 | 17 | 0 | 17 | 0 | 17 |
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| D013568 |
| Pathological Conditions, Signs and Symptoms |
| D009069 | Movement Disorders |
| D002493 | Central Nervous System Diseases |
| D007818 | Laryngeal Diseases |
| D012140 | Respiratory Tract Diseases |
| D010038 | Otorhinolaryngologic Diseases |
| Superiority |