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

NCT ID: NCT00848172

Last Updated: 2012-12-27

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

View full results

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

29 participants

Study Classification

INTERVENTIONAL

Study Start Date

2009-02-28

Study Completion Date

2010-11-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

Background:

* Essential tremor (ET) is a neurological disorder characterized by uncontrollable shaking. Several medications are used to treat ET; however, they are often only partly effective and can have side effects.
* Research studies have shown that octanol, a food additive similar to alcohol, can improve tremor in animals. Octanol is less likely to make people drunk than alcohol. Two earlier NIH studies found that one form of octanol, called 1-octanol, did improve tremor in some people and had few side effects.
* In the body, 1-octanol is converted to octanoic acid. Researchers are interested in finding out whether octanoic acid can help people with ET.

Objectives:

* To find out if octanoic acid can improve hand tremor in people with essential tremor.
* To measure levels of octanoic acid in the blood after it is taken.

Eligibility:

* Patients 21 years of age and older with ET, who are willing to abstain from alcohol, caffeine, and all medications as required by the study and who are willing and able to fast for up to 12 hours at a time.
* Participants may not be of Asian or Native American ancestry because of genetic susceptibilities to the intoxicating effects of the study drug.

Design:

* This study requires a 3-day hospital admission as well as two outpatient visits.
* Visit 1 (outpatient): Screening visit and blood alcohol level test
* Medical history, physical and neurological examination, a blood test, and an electrocardiogram to measure heart function. Women who are able to get pregnant will have a urine pregnancy test.
* Patients will consume 1.5 ounces of alcohol per drink (up to three drinks at least 30 minutes apart), and be tested to evaluate how the tremor responds. Researchers will draw blood to measure blood alcohol level about 1 hour after the first drink and closely monitor patients for signs of intoxication.
* Inpatient examination
* Preparation: Researchers will prepare a schedule to stop any tremor medications that patients might be on. Patients may not drink alcohol or eat or drink anything with caffeine, including chocolate, for at least 2 days before admission.
* Day 1: Vital signs, blood (and urine pregnancy) tests, and electrocardiogram. Patients will be asked to wear a tremor monitor, similar to a wristwatch. Patients will also have IV lines inserted for blood draws.
* Days 2 and 3: Randomized study medication (octanoic acid on one day, placebo on the other day). Patients will fast before taking the drug, but will be allowed to eat and drink after the tests are completed (around noon).
* Blood will be drawn before taking the study drug and again (a total of nine times) after taking the drug.
* Tremor will be measured during the study, before and after taking the drug.
* Visit 2 (outpatient): 4 to 7 days after discharge
* Blood test and an electrocardiogram, and a series of questionnaires regarding the study.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

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 points 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 parameters.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Essential Tremor

Keywords

Explore important study keywords that can help with search, categorization, and topic discovery.

Essential Tremor Octanol Octanoic Acid Ethanol Accelerometry

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Octanoic Acid

Group Type ACTIVE_COMPARATOR

Octanoic Acid

Intervention Type DRUG

4mg/kg

Placebo

Group Type PLACEBO_COMPARATOR

Placebo

Intervention Type DRUG

identical capsules

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Octanoic Acid

4mg/kg

Intervention Type DRUG

Placebo

identical capsules

Intervention Type DRUG

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

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 treatment 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
Minimum Eligible Age

21 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Mark Hallett

Chief, Human Motor Control Section

Responsibility Role PRINCIPAL_INVESTIGATOR

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, United States

Site Status

Countries

Review the countries where the study has at least one active or historical site.

United States

References

Explore related publications, articles, or registry entries linked to this study.

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 [RETIRED]: report of the Quality Standards Subcommittee of the American Academy of Neurology. Neurology. 2005 Jun 28;64(12):2008-20. doi: 10.1212/01.WNL.0000163769.28552.CD. Epub 2005 Jun 22.

Reference Type BACKGROUND
PMID: 15972843 (View on PubMed)

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. doi: 10.1002/mds.1184.

Reference Type BACKGROUND
PMID: 11746622 (View on PubMed)

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. doi: 10.1093/brain/124.11.2278.

Reference Type BACKGROUND
PMID: 11673328 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

09-N-0084

Identifier Type: -

Identifier Source: secondary_id

090084

Identifier Type: -

Identifier Source: org_study_id