This study will evaluate the effectiveness of 1-octanol, a substance similar to alcohol but
less intoxicating, for treating essential tremor. Essential tremor is an involuntary
shaking, usually of the hands, for which there is no satisfactory treatment. It affects
about 1.4 percent of the general U.S. population, with the figure climbing to nearly 4
percent among people over 40. Results of two previous NIH studies have shown 1-octanol to be
promising as a potential new treatment. This study will test the effectiveness of 1-octanol
on essential tremor at doses lower than those given previously.
Patients 21 years old and older with essential tremor may be eligible for this study.
Participants are admitted to the NIH Clinical Center for two treatment periods of 1 week
each, with a 1-week break at home between treatments. Before beginning treatment,
participants undergo a medical history, physical examination, blood and urine tests, and an
electrocardiogram (EKG). In addition, tremors are measured using accelerometry, a procedure
in which a small device, mounted on a piece of cardboard, is taped to the patient's hand for
about 30 minutes.
Patients are randomly assigned to one of two groups. One group takes 2 to 4 capsules of
1-octanol 3 times a day for 1 week, followed by a 1-week "washout" period (no treatment),
and then 2 to 4 capsules of placebo 3 times a day for 1 week. Following the same dosage
schedule, the second group takes placebo the first week, followed by the washout period and
then 1-octanol treatment. Blood pressure and pulse are measured at 15, 30, and 60 minutes
after the first dose of the day and then 3 times a day each day of hospitalization, EKG and
blood draws are done every other day during hospitalization, and blood is drawn again 1 week
after the end of the study. Patients evaluate their tremor daily according to a tremor scale
and are also rated according to an alcohol intoxication scale.
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 from? 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 the unmasking of spontaneous oscillation of neurons in the inferior
olive. Both ethanol and 1-octanol have been shown to reduce these spontaneous oscillations
in a animal model of essential tremor; however, 1-octanol does this at a dose much lower
than an intoxicating dose suggesting that it may be useful in the treatment of essential
tremor. Two pilot studies with 1-octanol in patients with essential tremor suggested it was
both efficacious and safe.
Objectives: The aim of the present study is to further assess efficacy of 1-octanol in
essential tremor in a double-blinded, placebo-controlled study.
Study population: Patients with alcohol-responsive essential tremor.
Design: Double-blind, placebo-controlled two-period cross-over design.
Outcome parameters: Primary outcome parameter is tremor as assessed by accelerometry,
secondary outcome measures are spiral drawing, subjective and clinical scoring.
Estimate of the outcome: 1-octanol at the dose of 32mg/kg three times a day will
significantly improve tremor in patients with alcohol-responsive essential tremor.
Anticipated risks and benefits: Besides the unusual taste, there are no anticipated risks
associated with 1-octanol ingestion. Patients may experience an improvement of their
Potential meaning for the field: Better treatment of essential tremor.
- INCLUSION CRITERIA:
14 patients with a clinical diagnosis of essential tremor will participate in the
study. Selection criterion is essential tremor with a history of ethanol
responsiveness. Informed consent will be obtained by any of the co-investigators.
Patients must be off any medications used to treat essential tremor such as mysoline or
propranolol for at least 2 weeks. Patients must withhold ethanol and caffeine 24 hours
prior to starting the treatment periods through the end of treatment periods, including
alcohol or caffeine containing over the counter medications. Ethanol and caffeine
consumption is allowed in the washout period.
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 medications that cannot be temporarily discontinued for the length of
Patients, who, for moral or religious reasons, do not wish to take a potentially
Patients with abnormalities on their baseline screening laboratory tests.
Women who are pregnant or lactating.
Patients under the age of 21.
Asians and Pacific Islanders.