Protocol Number: 09-N-0084

Title:

Double-Blind, Placebo Controlled Pilot-Study of Octanoic Acid in Essential Tremor

Number:

09-N-0084

Summary:

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 point 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 parameter.

Sponsoring Institute:

National Institute of Neurological Disorders and Stroke (NINDS)

Recruitment Detail

Type: Participants currently recruited/enrolled

Gender: Male & Female

Referral Letter Required: Yes

Population Exclusion(s): Children

Asian

American Indian or Alaskan Native

Eligibility Criteria:

INCLUSION CRITERIA:

- 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 treat 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

EXCLUSION CRITERIA:

- 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

- 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

Special Instructions:

Currently Not Provided

Keywords:

Essential Tremor

Octanol

Octanoic Acid

Ethanol

Accelerometry

Recruitment Keyword(s):

Essential Tremor

Condition(s):

Essential Tremor

Investigational Drug(s):

Octanoic Acid

Investigational Device(s):

None

Intervention(s):

Drug: Octanic Acid

Drug: Octanoic Acid

Supporting Site:

National Institute of Neurological Disorders and Stroke

Contact(s):

Patient Recruitment and Public Liaison Office
Building 61
10 Cloister Court
Bethesda, Maryland 20892-4754
Toll Free: 1-800-411-1222
TTY: 301-594-9774 (local),1-866-411-1010 (toll free)
Fax: 301-480-9793

Electronic Mail:prpl@mail.cc.nih.gov

Citation(s):

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: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2005 Jun 28;64(12):2008-20. Epub 2005 Jun 22.

Louis 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.

Stolze H, Petersen G, Raethjen J, Wenzelburger R, Deuschl G. The gait disorder of advanced essential tremor. Brain. 2001 Nov;124(Pt 11):2278-86

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