Octanoic Acid for Essential Tremor
- 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.
- To test different doses of octanoic acid to treat essential tremor.
- 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.
- 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 Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Dose Escalation Study of Oral Octanoic Acid in Patients With Essential Tremor|
- Dose-limiting toxicity [ Time Frame: 2 years ]
- Effect on tremor [ Time Frame: 2 years ]
|Study Start Date:||October 28, 2011|
|Study Completion Date:||July 18, 2012|
|Primary Completion Date:||July 18, 2012 (Final data collection date for primary outcome measure)|
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.
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.
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01468948
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Mark Hallett, M.D.||National Institute of Neurological Disorders and Stroke (NINDS)|