Clinical Trial: Octanoic Acid for Essential Tremor

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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

Brief Summary:

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 te
  

  Detailed Summary:

  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
  Sponsor: National Institute of Neurological Disorders and Stroke (NINDS)
  

  Current Primary Outcome: Dose-limiting toxicity [ Time Frame: 2 years ]
  
  

  Original Primary Outcome: Same as current
  
  

  Current Secondary Outcome: Effect on tremor [ Time Frame: 2 years ]
  
  

  Original Secondary Outcome: Same as current
  
  Information By: National Institutes of Health Clinical Center (CC)
  

  Dates:
  Date Received: November 8, 2011
  Date Started: October 28, 2011
  Date Completion:
  Last Updated: May 12, 2017
  Last Verified: July 18, 2012