Essential TremorPhase 1/2NCT00848172
Double-Blind, Placebo Controlled Pilot Study of Octanoic Acid in Essential Tremor
A Phase 1/2 study testing Octanoic Acid in people with Essential Tremor, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
Background: Essential tremor (ET) is a neurological disorder characterized by uncontrollable shaking. Several medications are used to treat ET; however, they are often only partly effective and can have side effects. Read more about this study
- Who is it for?
- Ages 21 years and older
- Conditions the study is for
- Essential Tremor
- What is being tested?
- Octanoic Acid
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 29 participants
- Where
- 1 siteUnited States
- Study dates
- Feb 2009to Nov 2010
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female patients with alcohol-responsive ET according to published clinical criteria
- Tremor in both upper limbs should be predominant feature of ET
- Subjects must be willing and safely able to comply with the study protocol and therefore abstain from any medication for the treatment of tremor for a period of at least 5 plasma half-lives of the individual drug prior to study participation. (For Propranolol/Inderal(Registered Trademark), Gabapentin/Neurontin(Registered Trademark), Topiramate/Topamax(Registered Trademark) this will be 4 days; for Primidone/Mysoline(Registered Trademark): 28 days).
- Subjects must be willing to refrain from alcohol and caffeine intake starting 48 hr prior to hospitalization until study termination
- Subject must be willing and able to fast for periods of up to 12 hours during the study
Who cannot join
- Patients with any other significant pathological finding in the neurological examination other than typical symptoms of ET
- Acute or chronic severe medical conditions which would preclude the subject from participating (e.g., severe heart disease NYHA grade 3 or 4, renal failure, hepatic failure, lung disease, uncontrolled hyperthyroidism)
- Subjects with diabetes mellitus, hypoglycemia or severe hyperlipidemia (must be documented by referring physician with copy of last fasting routine blood test within one year before the screening visit including glucose and lipid levels; according to NIH guidelines, fasting LDL levels of greater than or equal to 160 mg/dl are considered severe hyperlipidemia; if under treatment, LDL-levels less than 160 have to be documented to be eligible for the study)
- Subjects with active or past alcohol abuse or dependence
- Subjects with concomitant therapy with warfarin or NSAIDs, when taken on a regular basis and cannot be discontinued at least 14 days prior to study participation, because of potential interactions with octanoic acid (displacement of albumin binding in human serum)
- Subjects with clinically significant abnormalities on their baseline laboratory tests
Show all 11Show fewer
- Subjects aged less than 21 years
- Female subjects who are pregnant or lactating
- Subjects with cognitive impairment interfering with the ability to give informed consent or to cooperate during the study
- Subjects of Far East Asian or Native American descent, who may possess variant alleles of the genes for alcohol metabolism, i.e., alcohol dehydrogenase and aldehyde dehydrogenase, resulting in altered (slower) metabolism and potentially increased sensitivity to alcohols and their metabolites
- Subjects where no written informed consent is received or subjects who are unwilling to cooperate during the study
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892
About this study
Official title: Double-Blind, Placebo Controlled Pilot-Study of Octanoic Acid in Essential Tremor
Background:
- Essential tremor (ET) is a neurological disorder characterized by uncontrollable shaking. Several medications are used to treat ET; however, they are often only partly effective and can have side effects.
- Research studies have shown that octanol, a food additive similar to alcohol, can improve tremor in animals. Octanol is less likely to make people drunk than alcohol. Two earlier NIH studies found that one form of octanol, called 1-octanol, did improve tremor in some people and had few side effects.
- In the body, 1-octanol is converted to octanoic acid. Researchers are interested in finding out whether octanoic acid can help people with ET.
Read more
Objectives:
- To find out if octanoic acid can improve hand tremor in people with essential tremor.
- To measure levels of octanoic acid in the blood after it is taken.
Eligibility:
- Patients 21 years of age and older with ET, who are willing to abstain from alcohol, caffeine, and all medications as required by the study and who are willing and able to fast for up to 12 hours at a time.
- Participants may not be of Asian or Native American ancestry because of genetic susceptibilities to the intoxicating effects of the study drug.
Design:
- This study requires a 3-day hospital admission as well as two outpatient visits.
- Visit 1 (outpatient): Screening visit and blood alcohol level test
- Medical history, physical and neurological examination, a blood test, and an electrocardiogram to measure heart function. Women who are able to get pregnant will have a urine pregnancy test.
- Patients will consume 1.5 ounces of alcohol per drink (up to three drinks at least 30 minutes apart), and be tested to evaluate how the tremor responds. Researchers will draw blood to measure blood alcohol level about 1 hour after the first drink and closely monitor patients for signs of intoxication.
- Inpatient examination
- Preparation: Researchers will prepare a schedule to stop any tremor medications that patients might be on. Patients may not drink alcohol or eat or drink anything with caffeine, including chocolate, for at least 2 days before admission.
- Day 1: Vital signs, blood (and urine pregnancy) tests, and electrocardiogram. Patients will be asked to wear a tremor monitor, similar to a wristwatch. Patients will also have IV lines inserted for blood draws.
- Days 2 and 3: Randomized study medication (octanoic acid on one day, placebo on the other day). Patients will fast before taking the drug, but will be allowed to eat and drink after the tests are completed (around noon).
- Blood will be drawn before taking the study drug and again (a total of nine times) after taking the drug.
- Tremor will be measured during the study, before and after taking the drug.
- Visit 2 (outpatient): 4 to 7 days after discharge
- Blood test and an electrocardiogram, and a series of questionnaires regarding the study.
Read the detailed description
OBJECTIVE:
We propose a study to examine the safety and efficacy of octanoic acid in essential tremor (ET).
STUDY POPULATION:
We will study 19 adult subjects with ethanol-responsive ET.
DESIGN:
Octanoic acid will be tested in a double-blind, randomized, placebo-controlled, cross-over design in 19 patients with essential tremor. The active study medication and placebo will be administered as oral single morning doses on consecutive days in a randomized sequence. All subjects will receive a dose that was defined as being safe according to available toxicity data (4mg/kg) and will be monitored closely during the total inpatient study phase of three days (day 0: baseline; days 1-2: active study days).
OUTCOME MEASURES:
The primary outcome measure for this study will be the effect on tremor power of the dominant hand, 80 minutes after administration of the study substance, compared to placebo. Tremor power will be measured using accelerometry with loading to test central tremor component. Secondary outcome measures include recordings of tremor power as measured by accelerometry at multiple other time points up to 300 min after administration, also recorded from the non-dominant hand and without loading. The change in tremor severity documented by spirography and actigraphy as well as data collected regarding drug safety (laboratory testing, documentation of vital signs, adverse events questionnaire and intoxication scale) as well as the pharmacokinetic and pharmacodynamic properties will act as further secondary outcome parameters.
- Conditions
- Essential Tremor
- Being tested
- Octanoic Acid, Placebo
- Keywords
- Essential Tremor, Octanol, Octanoic Acid, Ethanol, Accelerometry
- Medical subject headings
- Essential Tremor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Octanoic AcidDrug
4mg/kg
PlaceboDrug
identical capsules
| Study group | Role | What they receive |
|---|---|---|
| Octanoic Acid | Active comparator | Not described Receives: Drug: Octanoic Acid |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Normalized Accelerometric Tremor Power, Dominant Hand, 80min After Administration, Weighted Condition
Postural tremor was measured using accelerometry with a motion sensor (accelerometer) placed at the dorsum of each hand, and tremor recorded simultaneously with surface-electromyography of wrist flexors and extensors for 2 minutes at each time-point. The recording was repeated with 1 lbs weight added to each wrist, which was described to record the central tremor component. The primary outcome measure was defined as tremor power of the central tremor component (after the addition of weight) 80 minutes after administration, measured at the dominant hand, normalized to baseline (baseline = 1), and comparing octanoic acid vs. placebo. Ratio of tremor power at 80 min divided by tremor power at baseline used for outcome measure calculation.
Measured: 80 min after administration of the study drug on day 1 and 2 of Visit 2
Secondary outcomes (3)
Normalized Tremor Power, 300 Min After Administration, Weighted Condition, Dominant Hand, OA vs Placebo
As described at the section for the primary outcome, normalized accelerometric tremor accelerometry was measured at other time-points to describe a time-course of effect. This stated secondary outcome compared normalized (baseline = 1) accelerometric at the last time-point 300 min post dose after OA vs Placebo. Ratios of tremor power at 300 min divided by tremor power at baseline used for outcome measure calculation.
Measured: 300 min post dose
TMax Octanoic Acid
Time to plasma peak OA
Measured: between 5 and 300 min post dose
PK: AUC After OA
Area under the curve of PA plasma levels after administration
Measured: 5 to 300 min post dose
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Feb 2009 (estimated)
- Study startFeb 2009
- Primary completionNov 2010
- Study completionNov 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Essential TremorStudies of the same condition, open and under way.
- More trials run by National Institute of Neurological Disorders and Stroke (NINDS)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 29 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Responsible party
- Principal investigator, Mark Hallett, National Institute of Neurological Disorders and Stroke (NINDS)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00848172
- Sponsor's protocol ID
- 090084
- Other IDs
- 09-N-0084
- Status last verified
- Nov 2012
- First submitted
- 19 Feb 2009
- Last updated
- 27 Dec 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Zesiewicz TA, Elble R, Louis ED, Hauser RA, Sullivan KL, Dewey RB Jr, Ondo WG, Gronseth GS, Weiner WJ; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: therapies for essential tremor [RETIRED]: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2005 Jun 28;64(12):2008-20. doi: 10.1212/01.WNL.0000163769.28552.CD. Epub 2005 Jun 22.
PubMed 15972843Louis ED, Barnes L, Albert SM, Cote L, Schneier FR, Pullman SL, Yu Q. Correlates of functional disability in essential tremor. Mov Disord. 2001 Sep;16(5):914-20. doi: 10.1002/mds.1184.
PubMed 11746622Stolze H, Petersen G, Raethjen J, Wenzelburger R, Deuschl G. The gait disorder of advanced essential tremor. Brain. 2001 Nov;124(Pt 11):2278-86. doi: 10.1093/brain/124.11.2278.
PubMed 11673328
Study at a glance
From the registry record, last updated by the sponsor on 27 Dec 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Double-Blind, Placebo Controlled Pilot-Study of Octanoic Acid in Essential Tremor
- ClinicalTrials.gov ID
- NCT00848172
- Acronym / sponsor ID
- 090084
- Conditions
- Essential Tremor
- Keywords
- Essential Tremor, Octanol, Octanoic Acid, Ethanol, Accelerometry
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 29 participants (actual)
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- Feb 2009
- Primary completion
- Nov 2010 (actual)
- Study completion
- Nov 2010 (actual)
- First posted
- 20 Feb 2009 (estimated)
- Results
- Posted 27 Dec 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Background:
- Essential tremor (ET) is a neurological disorder characterized by uncontrollable shaking. Several medications are used to treat ET; however, they are often only partly effective and can have side effects.
- Research studies have shown that octanol, a food additive similar to alcohol, can improve tremor in animals. Octanol is less likely to make people drunk than alcohol. Two earlier NIH studies found that one form of octanol, called 1-octanol, did improve tremor in some people and had few side effects.
- In the body, 1-octanol is converted to octanoic acid. Researchers are interested in finding out whether octanoic acid can help people with ET.
Objectives:
- To find out if octanoic acid can improve hand tremor in people with essential tremor.
- To measure levels of octanoic acid in the blood after it is taken.
Eligibility:
- Patients 21 years of age and older with ET, who are willing to abstain from alcohol, caffeine, and all medications as required by the study and who are willing and able to fast for up to 12 hours at a time.
- Participants may not be of Asian or Native American ancestry because of genetic susceptibilities to the intoxicating effects of the study drug.
Design:
- This study requires a 3-day hospital admission as well as two outpatient visits.
- Visit 1 (outpatient): Screening visit and blood alcohol level test
- Medical history, physical and neurological examination, a blood test, and an electrocardiogram to measure heart function. Women who are able to get pregnant will have a urine pregnancy test.
- Patients will consume 1.5 ounces of alcohol per drink (up to three drinks at least 30 minutes apart), and be tested to evaluate how the tremor responds. Researchers will draw blood to measure blood alcohol level about 1 hour after the first drink and closely monitor patients for signs of intoxication.
- Inpatient examination
- Preparation: Researchers will prepare a schedule to stop any tremor medications that patients might be on. Patients may not drink alcohol or eat or drink anything with caffeine, including chocolate, for at least 2 days before admission.
- Day 1: Vital signs, blood (and urine pregnancy) tests, and electrocardiogram. Patients will be asked to wear a tremor monitor, similar to a wristwatch. Patients will also have IV lines inserted for blood draws.
- Days 2 and 3: Randomized study medication (octanoic acid on one day, placebo on the other day). Patients will fast before taking the drug, but will be allowed to eat and drink after the tests are completed (around noon).
- Blood will be drawn before taking the study drug and again (a total of nine times) after taking the drug.
- Tremor will be measured during the study, before and after taking the drug.
- Visit 2 (outpatient): 4 to 7 days after discharge
- Blood test and an electrocardiogram, and a series of questionnaires regarding the study.
Detailed description
OBJECTIVE:
We propose a study to examine the safety and efficacy of octanoic acid in essential tremor (ET).
STUDY POPULATION:
We will study 19 adult subjects with ethanol-responsive ET.
DESIGN:
Octanoic acid will be tested in a double-blind, randomized, placebo-controlled, cross-over design in 19 patients with essential tremor. The active study medication and placebo will be administered as oral single morning doses on consecutive days in a randomized sequence. All subjects will receive a dose that was defined as being safe according to available toxicity data (4mg/kg) and will be monitored closely during the total inpatient study phase of three days (day 0: baseline; days 1-2: active study days).
OUTCOME MEASURES:
The primary outcome measure for this study will be the effect on tremor power of the dominant hand, 80 minutes after administration of the study substance, compared to placebo. Tremor power will be measured using accelerometry with loading to test central tremor component. Secondary outcome measures include recordings of tremor power as measured by accelerometry at multiple other time points up to 300 min after administration, also recorded from the non-dominant hand and without loading. The change in tremor severity documented by spirography and actigraphy as well as data collected regarding drug safety (laboratory testing, documentation of vital signs, adverse events questionnaire and intoxication scale) as well as the pharmacokinetic and pharmacodynamic properties will act as further secondary outcome parameters.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Octanoic Acid | Active comparator | Drug: Octanoic Acid |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 21 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Male or female patients with alcohol-responsive ET according to published clinical criteria
- Tremor in both upper limbs should be predominant feature of ET
- Subjects must be willing and safely able to comply with the study protocol and therefore abstain from any medication for the treatment of tremor for a period of at least 5 plasma half-lives of the individual drug prior to study participation. (For Propranolol/Inderal(Registered Trademark), Gabapentin/Neurontin(Registered Trademark), Topiramate/Topamax(Registered Trademark) this will be 4 days; for Primidone/Mysoline(Registered Trademark): 28 days).
- Subjects must be willing to refrain from alcohol and caffeine intake starting 48 hr prior to hospitalization until study termination
- Subject must be willing and able to fast for periods of up to 12 hours during the study
Key exclusion criteria (11 listed)
- Patients with any other significant pathological finding in the neurological examination other than typical symptoms of ET
- Acute or chronic severe medical conditions which would preclude the subject from participating (e.g., severe heart disease NYHA grade 3 or 4, renal failure, hepatic failure, lung disease, uncontrolled hyperthyroidism)
- Subjects with diabetes mellitus, hypoglycemia or severe hyperlipidemia (must be documented by referring physician with copy of last fasting routine blood test within one year before the screening visit including glucose and lipid levels; according to NIH guidelines, fasting LDL levels of greater than or equal to 160 mg/dl are considered severe hyperlipidemia; if under treatment, LDL-levels less than 160 have to be documented to be eligible for the study)
- Subjects with active or past alcohol abuse or dependence
- Subjects with concomitant therapy with warfarin or NSAIDs, when taken on a regular basis and cannot be discontinued at least 14 days prior to study participation, because of potential interactions with octanoic acid (displacement of albumin binding in human serum)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Octanoic Acid4mg/kg | Drug | Octanoic Acid |
| Placeboidentical capsules | Drug | Placebo |
Primary outcome
Normalized Accelerometric Tremor Power, Dominant Hand, 80min After Administration, Weighted Condition
Time frame: 80 min after administration of the study drug on day 1 and 2 of Visit 2
Postural tremor was measured using accelerometry with a motion sensor (accelerometer) placed at the dorsum of each hand, and tremor recorded simultaneously with surface-electromyography of wrist flexors and extensors for 2 minutes at each time-point. The recording was repeated with 1 lbs weight added to each wrist, which was described to record the central tremor component. The primary outcome measure was defined as tremor power of the central tremor component (after the addition of weight) 80 minutes after administration, measured at the dominant hand, normalized to baseline (baseline = 1), and comparing octanoic acid vs. placebo. Ratio of tremor power at 80 min divided by tremor power at baseline used for outcome measure calculation.
3 secondary outcomes
Normalized Tremor Power, 300 Min After Administration, Weighted Condition, Dominant Hand, OA vs Placebo
Time frame: 300 min post dose
TMax Octanoic Acid
Time frame: between 5 and 300 min post dose
PK: AUC After OA
Time frame: 5 to 300 min post dose
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Dec 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 15972843Zesiewicz TA, Elble R, Louis ED, Hauser RA, Sullivan KL, Dewey RB Jr, Ondo WG, Gronseth GS, Weiner WJ; Quality Standards Subcommittee of the American Academy of Neurology. Practice parameter: therapies for essential tremor [RETIRED]: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2005 Jun 28;64(12):2008-20. doi: 10.1212/01.WNL.0000163769.28552.CD. Epub 2005 Jun 22.
- Background: PubMed 11746622Louis ED, Barnes L, Albert SM, Cote L, Schneier FR, Pullman SL, Yu Q. Correlates of functional disability in essential tremor. Mov Disord. 2001 Sep;16(5):914-20. doi: 10.1002/mds.1184.
- Background: PubMed 11673328Stolze H, Petersen G, Raethjen J, Wenzelburger R, Deuschl G. The gait disorder of advanced essential tremor. Brain. 2001 Nov;124(Pt 11):2278-86. doi: 10.1093/brain/124.11.2278.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Octanoic Acid in people with Essential Tremor, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Dec 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Dec 2012). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Normalized Accelerometric Tremor Power, Dominant Hand, 80min After Administration, Weighted Condition (time frame: 80 min after administration of the study drug on day 1 and 2 of Visit 2). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00848172, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Dec 2012.