This study will evaluate the safety and effectiveness of the food additive 1-octanol for
treating essential tremor. This disorder, which is an involuntary shaking, usually of the
hands, has no satisfactory treatment. It affects more than one of every 100 people in the
general population, with the figure climbing to nearly 4 in every hundred among people over
40 years old. In animal studies, 1-octanol reduced chemically induced tremors in rats.
This study will test the effects of the accepted daily intake of 1-octanol (1 milligram per
kilogram of body weight) on essential tremor in humans.
Patients with essential tremor 21 years old and older who wish to enroll in this study will
undergo eligibility screening with a medical history and physical examination that includes
tests for thyroid, liver and kidney problems. Participants will be randomly assigned to
receive either 1-octanol or a placebo (an inactive substance). Patients in both groups will
have an intravenous catheter (a thin, plastic tube) placed in an arm vein for collecting
blood samples during the study. Those in the 1-octanol group will be given a 1-octanol
capsule; the placebo group will receive a look-alike capsule containing no active
ingredient. Neither the patient nor the doctor will know which patients are taking
1-octanol or placebo until the end of the study.
Tremors will be measured once before the catheter is placed, every 15 minutes during the
first 2 hours after taking the capsule, twice during the third hour (30 minutes apart), and
once again after 5 hours. The tremors are measured using procedures called accelerometry
and surface electromyography. For these procedures, electrodes are taped to the skin;
needles are not used. Blood samples will be collected once before taking the capsule, every
15 minutes for the first hour and a half after taking the capsule and again at 2 hours, 4
hours and 5 hours after taking the capsule. Vital signs (blood pressure, pulse, and
respiratory rate) will be measured every 15 minutes during the first 2 hours of taking the
capsule, every 30 minutes during the third hour, and again at 4 hours and 5 hours.
Participants will stay in the hospital overnight for observation and return after 3 days for
a follow-up physical examination, including a blood test.
Essential tremor (ET) is the most common movement disorder; however, there is currently no
satisfactory drug treatment. The neural mechanisms underlying ET remain unknown. One of
the prevalent hypotheses is that ET is a result of a defective mechanism that normally
dampens the natural oscillations of inferior olive (IO) neurons whose intrinsic oscillatory
activity is attributed to the presence of low threshold calcium channels (LTCC). 1-Octanol
is known to inhibit LTCC of olivary neurons and was found to reduce the tremor induced in
rats with harmaline, an alkaloid known to hyperpolarize IO neurons increasing their tendency
to fire rhythmically at rest. The aim of this study is to assess the effects of 1-octanol
on ET in humans. This study is designed as a double-blind, placebo-controlled, single-dose
trial in untreated patients with ET. Electromyography (EMG) and acclerometry are used to
assess tremor before and after 1-octanol administration. The accepted daily intake (ADI) of
1-octanol (1 mg/kg/d) as a food additive will be given as a single dose. Toxicity from
octanol will be monitored clinically and by liver function and electrolyte measurements.
Patients with essential tremor affecting the upper limbs who are 21 years of age or older.
Patients who are not taking medications for essential tremor or any other medical
condition for at least 2 weeks.
Patients who have not consumed alcohol or cold medications containing alcohol for at least
24 hours prior to the day of the study.
Women must not be pregnant or lactating. Women of childbearing age must use birth control
while participating in this study.
Patients must not have any neurological disease other than tremor (e.g., Parkinson's
Patients must not have evidence of thyroid, liver, kidney or chronic lung disease.