Octanoic Acid for Essential Tremor

NCT01468948 | Completed Phase 1

• 2 other identifiers: 12002412-N-0024
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

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 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.

Conditions

Essential Tremor

Keywords

Essential Tremor; Tremor; Octanol; Octanoic Acid

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity

  2 years

Secondary Outcomes (1)

• Effect on tremor

  2 years

Interventions

Octanoic Acid DRUG

Eligibility Criteria

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

You may qualify if:

• 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

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 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)

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 (4)

• Bain P, Brin M, Deuschl G, Elble R, Jankovic J, Findley L, Koller WC, Pahwa R. Criteria for the diagnosis of essential tremor. Neurology. 2000;54(11 Suppl 4):S7. No abstract available.

  PMID: 10854345 BACKGROUND

• Ashitani J, Matsumoto N, Nakazato M. Effect of octanoic acid-rich formula on plasma ghrelin levels in cachectic patients with chronic respiratory disease. Nutr J. 2009 Jun 16;8:25. doi: 10.1186/1475-2891-8-25.

  PMID: 19527531 BACKGROUND

• Bach AC, Babayan VK. Medium-chain triglycerides: an update. Am J Clin Nutr. 1982 Nov;36(5):950-62. doi: 10.1093/ajcn/36.5.950.

  PMID: 6814231 BACKGROUND

• Voller B, Lines E, McCrossin G, Tinaz S, Lungu C, Grimes G, Starling J, Potti G, Buchwald P, Haubenberger D, Hallett M. Dose-escalation study of octanoic acid in patients with essential tremor. J Clin Invest. 2016 Apr 1;126(4):1451-7. doi: 10.1172/JCI83621. Epub 2016 Feb 29.

  PMID: 26927672 DERIVED

MeSH Terms

Conditions

Essential Tremor; Tremor

Interventions

octanoic acid

Condition Hierarchy (Ancestors)

Movement Disorders; Central Nervous System Diseases; Nervous System Diseases; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Mark Hallett, M.D.

  National Institute of Neurological Disorders and Stroke (NINDS)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 8, 2011
• First Posted: November 10, 2011
• Study Start: October 28, 2011
• Primary Completion: July 18, 2012
• Study Completion: July 18, 2012
• Last Updated: December 16, 2019

Record last verified: 2012-07-18

Locations

US (1)