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

NCT00848172 | Completed Phase 1 Results

• 2 other identifiers: 09008409-N-0084
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Essential Tremor

Keywords

Essential Tremor; Octanol; Octanoic Acid; Ethanol; Accelerometry

Outcome Measures

Primary Outcomes (1)

• Normalized Accelerometric Tremor Power, Dominant Hand, 80min After Administration, Weighted Condition

  Postural tremor was measured using accelerometry with a motion sensor (accelerometer) placed at the dorsum of each hand, and tremor recorded simultaneously with surface-electromyography of wrist flexors and extensors for 2 minutes at each time-point. The recording was repeated with 1 lbs weight added to each wrist, which was described to record the central tremor component. The primary outcome measure was defined as tremor power of the central tremor component (after the addition of weight) 80 minutes after administration, measured at the dominant hand, normalized to baseline (baseline = 1), and comparing octanoic acid vs. placebo. Ratio of tremor power at 80 min divided by tremor power at baseline used for outcome measure calculation.

  80 min after administration of the study drug on day 1 and 2 of Visit 2

Secondary Outcomes (3)

• Normalized Tremor Power, 300 Min After Administration, Weighted Condition, Dominant Hand, OA vs Placebo

  300 min post dose

• TMax Octanoic Acid

  between 5 and 300 min post dose

• PK: AUC After OA

  5 to 300 min post dose

Study Arms (2)

Octanoic Acid

ACTIVE COMPARATOR

Drug: Octanoic Acid

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Octanoic Acid DRUG

4mg/kg

Octanoic Acid

Placebo DRUG

identical capsules

Placebo

Eligibility Criteria

• Age: 21 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• National Institute of Neurological Disorders and Stroke (NINDS): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• 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.

  PMID: 15972843 BACKGROUND

• 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.

  PMID: 11746622 BACKGROUND

• 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.

  PMID: 11673328 BACKGROUND

MeSH Terms

Conditions

Essential Tremor

Interventions

octanoic acid

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases

Results Point of Contact

• Title: Mark Hallett
• Organization: NINDS

hallettm@ninds.nih.gov

301-496-9526

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Chief, Human Motor Control Section

Study Record Dates

• First Submitted: February 19, 2009
• First Posted: February 20, 2009
• Study Start: February 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: November 1, 2010
• Last Updated: December 27, 2012
• Results First Posted: December 27, 2012

Record last verified: 2012-11

Locations

US (1)