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.
INCLUSION CRITERIA: 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). EXCLUSION CRITERIA: 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