Octanoic Acid for Essential Tremor

December 13, 2019 updated by: National Institute of Neurological Disorders and Stroke (NINDS)

Dose Escalation Study of Oral Octanoic Acid in Patients With Essential Tremor

Background:

- Essential tremor (ET) is a condition of out-of-control shaking. Several drugs are used to treat ET. However, they are often only partly helpful and can have side effects. Many people with ET get some relief from drinking alcohol. Octanol, a food additive similar to alcohol, can improve tremor in animals and is less likely to make people feel drunk. One form of octanol, called 1-octanol, has been shown to improve tremor in some people and had few side effects. 1-octanol is converted to octanoic acid, and research suggests that octanoic acid itself might suppress ET with no significant side effects such as drunkenness. Researchers want to see what dose of octanoic acid is most useful in reducing ET.

Objectives:

- To test different doses of octanoic acid to treat essential tremor.

Eligibility:

  • Individuals at least 21 years of age who have ET that responds to treatment with alcohol.
  • Participants must be able to stop taking certain ET medications during the study.

Design:

  • This study requires three visits. Visit 1 is a screening visit that will take up to 5 hours. Visit 2 is a 2- to 3-day inpatient admission to the National Institutes of Health Clinical Center. Visit 3 is a followup outpatient visit 1 to 2 weeks after the hospital admission.
  • At the screening visit, participants will have a physical exam, neurological exam, and medical history. Blood and urine samples will be collected. Participants will also have an alcohol dose test to measure the tremor s response to alcohol.
  • For the study visit, participants will enter the hospital for testing. Participants will have the study drug and test the tremor's response to it. Frequent blood samples will be collected.
  • One to two weeks after leaving the hospital, participants will have a final followup study visit. Blood samples will be collected.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

OBJECTIVE:

To determine the maximum tolerated dose of oral octanoic acid (OA) in patients with essential tremor. Further study objectives include the evaluation of the efficacy and tolerability of octanoic acid with escalation doses, as well as the pharmacokinetic and pharmacodynamic profile.

STUDY POPULATION:

Up to 30 subjects with ethanol-responsive essential tremor (ET) will be included in the study. Subjects will be recruited in groups of 6 per dose level.

DESIGN:

The study objectives will be tested using a 3+3 dose escalation design. Per dose level, 3 subjects will be recruited, and dose levels will be 8, 16, 32, 64, and 128 mg/kg, with additional 3 subjects at the same level if one of the three subjects exhibits dose limit toxicity. Subjects will undergo a screening visit, followed by a 2 to 3-day inpatient admission during which the study drug OA will be administered. An outpatient follow-up visit will conclude the study.

OUTCOME MEASURES:

The primary outcome will be measured by evaluating dose-limiting toxicity, which will be reached once 2 or more subjects exhibit a grade 2 adverse event (CTCAE) on the same dose-level, which is related to OA. The dose below the level at which 2 or more grade 2 OA-related adverse events have been observed, will then be defined as maximum tolerated dose (MTD) and the study stopped. Toxicity for the primary outcome will be monitored by an unblinded independent data safety monitoring board (DSMB), who will determine when the primary outcome is reached.

Secondary measures will include safety measures such as routine laboratory parameters, EKG measures, vital signs as well as a standardized assessment for signs of intoxication. Additional secondary outcome measures will include efficacy measures such as tremor accelerometry and digital spiral analysis, as well as a standardized clinical tremor rating scale. Furthermore, pharmacokinetic sampling will be performed.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Maryland
      • Bethesda, Maryland, United States, 20892
        • National Institutes of Health Clinical Center, 9000 Rockville Pike

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

17 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

  • INCLUSION CRITERIA:
  • Diagnosis of essential tremor with bilateral hand tremor as the predominant feature, which is known to be responsive to ethanol.
  • Unequivocal accelerometric tremor of both hands on screening examination (bilateral central tremor component during postural tremor accelerometry, consistent with ET)
  • Reduction of accelerometric tremor power of at least 35% following a formal ethanol challenge during the screening visit.
  • Subjects must be willing and safely able to 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 , Gabapentin/Neurontin this will be 1 day; for Primidone/Mysoline : 26 days).

Subjects must be willing to refrain from alcohol and drinks or food containing caffeine starting 48 hours prior to the study visits

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 concomitant therapy with warfarin or NSAIDs (other than aspirin), 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)(Noctor et al. 1992)
  • Established diagnosis of diabetes mellitus, as fasting-periods of up to 12 hours are required in the protocol.
  • Subjects with active or past alcohol abuse or dependence (AUDIT score greater than or equal to 8)
  • Elevated liver function parameters (AST, ALT, GGT), higher than the 1.5 fold upper limit of the normal range (as defined by the NIH Clinical Center Laboratory Medicine Department), or any other clinically significant abnormalities on their baseline laboratory tests. The limit for AST therefore will be 51 U/l, for ALT 62 U/L, and GGT 128 U/l.
  • Female subjects who are pregnant or breastfeeding
  • Subjects aged < 21 years
  • Known flushing symptoms after alcohol intake or allergy to alcohol (any yes answer in the standardized Alcohol Flushing Questionnaire)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Dose-limiting toxicity
Time Frame: 2 years
2 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Effect on tremor
Time Frame: 2 years
2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
National Institute of Neurological Disorders and Stroke (NINDS)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 28, 2011

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
July 18, 2012

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
July 18, 2012

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
November 8, 2011

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 8, 2011

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
November 10, 2011

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 16, 2019

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 13, 2019

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 18, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 120024
  • 12-N-0024

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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