Essential TremorPhase 1NCT00016679
1-Octanol to Treat Essential Tremor
A Phase 1 study testing 1-Octanol in people with Essential Tremor, run by National Institute of Neurological Disorders and Stroke (NINDS) at 1 site in United States.
Trial summary
This study will determine the optimal dose of 1-octanol that will safely reduce tremors in patients with essential tremor-a disorder in which the hands, and sometimes the head, shake involuntarily. Current treatments may be ineffective or produce unwanted side effects. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Essential Tremor
- What is being tested?
- 1-Octanol
- How many people
- 42 participants
- Where
- 1 siteUnited States
- Study dates
- May 2001to Mar 2004
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with essential tremor with a history or ethanol responsiveness.
- Patients must be off any medications used to treat essential tremor such as mysoline or propranalol for at least 2 weeks.
- Patients must withhold ethanol and caffeine from 24 hours prior to starting the study until study termination (10 days).
Who cannot join
- Patients with abnormalities on neurologic exam other than tremor.
- Patients with a history of chronic alcohol dependence.
- Patients with chronic medical conditions such as renal failure, hepatic failure and chronic lung disease.
- Patients on other chronic medications that cannot be temporarily discontinued for the length of the study (10 days).
- Patients, who for moral or religious reasons do not wish to take a potentially intoxicating drug.
- Patients with abnormalities on their baseline screening laboratory tests.
- Women who are pregnant or lactating.
- People of Asian decent who may differ pharmocogenetically with respect to alcohol and aldehyde dehydrogenase and may have increased sensitivity to alcohols and their metabolites
Trial locations and contacts
1 site in 1 country.
United States1 site
National Institute of Neurological Disorders and Stroke (NINDS)
Bethesda, Maryland, 20892
About this study
Official title: Dose Finding Study of 1-Octanol in Essential Tremor
This study will determine the optimal dose of 1-octanol that will safely reduce tremors in patients with essential tremor-a disorder in which the hands, and sometimes the head, shake involuntarily. Current treatments may be ineffective or produce unwanted side effects. Ethanol (the chemical in beer and wine that causes intoxication) reduces tremor in many patients, but patients generally don't use it regularly because it interferes with daily activities. Laboratory studies show that 1-octanol, a drug that is similar to ethanol, may have the same beneficial effect on tremors with less likelihood of intoxication.
Patients 21 years of age and older with essential tremor may be eligible for this 10-day study. Candidates will be evaluated with a neurological examination, blood tests, urinalysis and electrocardiogram (EKG). Those enrolled will be admitted to the hospital for 4 days for 1-octanol administration and monitoring. On day 1, patients will have a medical history and physical examination. A catheter (a thin plastic tube) will be placed in a vein of the forearm for sampling blood. Patients will take one 1-octanol capsule (at one of seven doses) by mouth and will be monitored for tremors and drug side effects. Blood will be sampled periodically in the first 3 hours to determine 1-octanol blood levels. On days 2 and 3, patients will be monitored for additional side effects. On days 3 and 4, laboratory tests (blood and urine) will be done to evaluate liver and kidney function. On day 4, the catheter will be removed and the patient will be discharged from the hospital. A follow-up visit will be scheduled 1 week after discharge for a physical examination and blood, urine and EKG tests.
Read the detailed description
Essential tremor is a very common movement disorder affecting approximately 1.4% of the population. Response to medications such as beta blockers and mysoline may be only partial or be accompanied by intolerable side effects. Roughly 80% of patients have significant tremor reduction to ethanol although daily use of this as a treatment has potentially serious social and legal consequences. The leading hypothesis for the pathophysiology of essential tremor is unmasking of spontaneous oscillation of neurons in the inferior olive. Both ethanol and 1-octanol have been shown to reduce these spontaneous oscillations in an animal model of essential tremor; however, 1-octanol dose this at a dose much lower than an intoxicating dose suggesting that it may be useful in the treatment of essential tremor. Our initial study with 1-octanol at a low, single dose in patients with essential tremor suggested it was both efficacious and safe.
This present study is planned to identify a maximum tolerated dose and broaden the safety and efficacy data in humans. Additionally, we hope to collect further information about the pharmacokinetics of 1-octanol. This study is designed as a phase Ia, unblinded, inpatient study of adults with essential tremor receiving escalating doses of 1-octanol. Cohorts of three will begin dose escalation at the dose previously studied. Each cohort will be followed in inpatient setting for 72 hours ( and outpatient for 1 additional week) during which adverse events, pharmacokinetics and efficacy will be assessed. If no subject achieves dose-limiting toxicity, 3 additional subjects will be recruited to receive the next higher dose. If 1/3 subjects achieves dose-limiting toxicity, the next cohort will receive the same dose. Dose limiting toxicity is defined as the dose that produces dose-limiting toxicity in at least 2 subjects. Maximum tolerated dose will be defined as the next lower dose.
With this study, we hope to identify a range of doses that may useful in the treatment of essential tremor and combined with the pharmacokinetic and efficacy data, design a protocol to study multiple dose regimens over longer time periods.
- Conditions
- Essential Tremor
- Being tested
- 1-Octanol
- Keywords
- Pharmacokinetics, Metabolism, Toxicity, Side Effects, Essential Tremor, Tremor, Movement Disorder
- Medical subject headings
- Essential Tremor, Tremor, Movement Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
1-OctanolDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2001 (estimated)
- Study startMay 2001
- Study completionMar 2004
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- 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
- Primary purpose
- Treatment
- Enrolment
- 42 participants
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00016679
- Sponsor's protocol ID
- 010178
- Other IDs
- 01-N-0178
- Status last verified
- Mar 2004
- First submitted
- 24 May 2001
- Last updated
- 4 Mar 2008
- Results posted
- No
Publications
Lyon RC, McComb JA, Schreurs J, Goldstein DB. A relationship between alcohol intoxication and the disordering of brain membranes by a series of short-chain alcohols. J Pharmacol Exp Ther. 1981 Sep;218(3):669-75.
PubMed 7264950Hellwig J, Jackh R. Differential prenatal toxicity of one straight-chain and five branched-chain primary alcohols in rats. Food Chem Toxicol. 1997 May;35(5):489-500. doi: 10.1016/s0278-6915(97)00007-0.
PubMed 9216748Bal T, McCormick DA. Synchronized oscillations in the inferior olive are controlled by the hyperpolarization-activated cation current I(h). J Neurophysiol. 1997 Jun;77(6):3145-56. doi: 10.1152/jn.1997.77.6.3145.
PubMed 9212264
Study at a glance
From the registry record, last updated by the sponsor on 4 Mar 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Finding Study of 1-Octanol in Essential Tremor
- ClinicalTrials.gov ID
- NCT00016679
- Acronym / sponsor ID
- 010178
- Conditions
- Essential Tremor
- Keywords
- Pharmacokinetics, Metabolism, Toxicity, Side Effects, Essential Tremor, Tremor, Movement Disorder
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 42 participants
- Lead sponsor
- National Institute of Neurological Disorders and Stroke (NINDS)US National Institutes of Health
- Study start
- May 2001
- Study completion
- Mar 2004
- First posted
- 25 May 2001 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will determine the optimal dose of 1-octanol that will safely reduce tremors in patients with essential tremor-a disorder in which the hands, and sometimes the head, shake involuntarily. Current treatments may be ineffective or produce unwanted side effects. Ethanol (the chemical in beer and wine that causes intoxication) reduces tremor in many patients, but patients generally don't use it regularly because it interferes with daily activities. Laboratory studies show that 1-octanol, a drug that is similar to ethanol, may have the same beneficial effect on tremors with less likelihood of intoxication.
Patients 21 years of age and older with essential tremor may be eligible for this 10-day study. Candidates will be evaluated with a neurological examination, blood tests, urinalysis and electrocardiogram (EKG). Those enrolled will be admitted to the hospital for 4 days for 1-octanol administration and monitoring. On day 1, patients will have a medical history and physical examination. A catheter (a thin plastic tube) will be placed in a vein of the forearm for sampling blood. Patients will take one 1-octanol capsule (at one of seven doses) by mouth and will be monitored for tremors and drug side effects. Blood will be sampled periodically in the first 3 hours to determine 1-octanol blood levels. On days 2 and 3, patients will be monitored for additional side effects. On days 3 and 4, laboratory tests (blood and urine) will be done to evaluate liver and kidney function. On day 4, the catheter will be removed and the patient will be discharged from the hospital. A follow-up visit will be scheduled 1 week after discharge for a physical examination and blood, urine and EKG tests.
Detailed description
Essential tremor is a very common movement disorder affecting approximately 1.4% of the population. Response to medications such as beta blockers and mysoline may be only partial or be accompanied by intolerable side effects. Roughly 80% of patients have significant tremor reduction to ethanol although daily use of this as a treatment has potentially serious social and legal consequences. The leading hypothesis for the pathophysiology of essential tremor is unmasking of spontaneous oscillation of neurons in the inferior olive. Both ethanol and 1-octanol have been shown to reduce these spontaneous oscillations in an animal model of essential tremor; however, 1-octanol dose this at a dose much lower than an intoxicating dose suggesting that it may be useful in the treatment of essential tremor. Our initial study with 1-octanol at a low, single dose in patients with essential tremor suggested it was both efficacious and safe.
This present study is planned to identify a maximum tolerated dose and broaden the safety and efficacy data in humans. Additionally, we hope to collect further information about the pharmacokinetics of 1-octanol. This study is designed as a phase Ia, unblinded, inpatient study of adults with essential tremor receiving escalating doses of 1-octanol. Cohorts of three will begin dose escalation at the dose previously studied. Each cohort will be followed in inpatient setting for 72 hours ( and outpatient for 1 additional week) during which adverse events, pharmacokinetics and efficacy will be assessed. If no subject achieves dose-limiting toxicity, 3 additional subjects will be recruited to receive the next higher dose. If 1/3 subjects achieves dose-limiting toxicity, the next cohort will receive the same dose. Dose limiting toxicity is defined as the dose that produces dose-limiting toxicity in at least 2 subjects. Maximum tolerated dose will be defined as the next lower dose.
With this study, we hope to identify a range of doses that may useful in the treatment of essential tremor and combined with the pharmacokinetic and efficacy data, design a protocol to study multiple dose regimens over longer time periods.
Study design
- Primary purpose
- Treatment
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (3 listed)
- Patients with essential tremor with a history or ethanol responsiveness.
- Patients must be off any medications used to treat essential tremor such as mysoline or propranalol for at least 2 weeks.
- Patients must withhold ethanol and caffeine from 24 hours prior to starting the study until study termination (10 days).
Key exclusion criteria (8 listed)
- Patients with abnormalities on neurologic exam other than tremor.
- Patients with a history of chronic alcohol dependence.
- Patients with chronic medical conditions such as renal failure, hepatic failure and chronic lung disease.
- Patients on other chronic medications that cannot be temporarily discontinued for the length of the study (10 days).
- Patients, who for moral or religious reasons do not wish to take a potentially intoxicating drug.
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 |
|---|---|---|
| 1-Octanol | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Mar 2008.
- Background: PubMed 7264950Lyon RC, McComb JA, Schreurs J, Goldstein DB. A relationship between alcohol intoxication and the disordering of brain membranes by a series of short-chain alcohols. J Pharmacol Exp Ther. 1981 Sep;218(3):669-75.
- Background: PubMed 9216748Hellwig J, Jackh R. Differential prenatal toxicity of one straight-chain and five branched-chain primary alcohols in rats. Food Chem Toxicol. 1997 May;35(5):489-500. doi: 10.1016/s0278-6915(97)00007-0.
- Background: PubMed 9212264Bal T, McCormick DA. Synchronized oscillations in the inferior olive are controlled by the hyperpolarization-activated cation current I(h). J Neurophysiol. 1997 Jun;77(6):3145-56. doi: 10.1152/jn.1997.77.6.3145.
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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 study testing 1-Octanol 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 3 inclusion and 8 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 4 Mar 2008. 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. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00016679, 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 4 Mar 2008.