Octanoic acid in alcohol-responsive essential tremor: A randomized controlled study

Dietrich Haubenberger, Gayle McCrossin, Codrin Lungu, Elaine Considine, Camilo Toro, Fatta B. Nahab, Sungyoung Auh, Peter Buchwald, George J. Grimes, Judith Starling, Gopal Potti, Linda Scheider, Daniel Kalowitz, Daniel Bowen, Andrea Carnie, Mark Hallett

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Objective: To assess safety and efficacy of an oral, single, low dose of octanoic acid (OA) in subjects with alcohol-responsive essential tremor (ET). Methods: We conducted a double-blind, placebo-controlled, crossover, phase I/II clinical trial evaluating the effect of 4 mg/kg OA in 19 subjects with ET. The primary outcome was accelerometric postural tremor power of the dominant hand 80 minutes after administration. Secondary outcomes included digital spiral analysis, pharmacokinetic sampling, as well as safety measures. Results: OA was safe and well tolerated. Nonserious adverse events were mild (Common Terminology Criteria for Adverse Events grade 1) and equally present after OA and placebo. At the primary outcome, OA effects were not different from placebo. Secondary outcome analyses of digital spiral analysis, comparison across the entire time course in weighted and nonweighted accelerometry, as well as nondominant hand tremor power did not show a benefit of OA over placebo. The analysis of individual time points showed that OA improved tremor at 300 minutes (dominant hand, F1,16 = 5.49, p = 0.032 vs placebo), with a maximum benefit at 180 minutes after OA (both hands, F1,16 = 6.1, p = 0.025). Conclusions: Although the effects of OA and placebo at the primary outcome were not different, secondary outcome measures suggest superiority of OA in reducing tremor at later time points, warranting further trials at higher dose levels. Classification of evidence: This study provides Class I evidence that a single 4-mg/kg dose of OA is not effective in reducing postural tremor in patients with ET at a primary outcome of 80 minutes, but is effective for a secondary outcome after 180 minutes.

Original languageEnglish
Pages (from-to)933-940
Number of pages8
JournalNeurology
Volume80
Issue number10
DOIs
StatePublished - Mar 5 2013

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Essential Tremor
Alcohols
Tremor
Placebos
Hand
octanoic acid
Controlled
Alcohol
Placebo
Accelerometry
Safety
Phase II Clinical Trials
Clinical Trials, Phase I
Terminology
Dose
Pharmacokinetics

ASJC Scopus subject areas

  • Clinical Neurology
  • Arts and Humanities (miscellaneous)

Cite this

Haubenberger, D., McCrossin, G., Lungu, C., Considine, E., Toro, C., Nahab, F. B., ... Hallett, M. (2013). Octanoic acid in alcohol-responsive essential tremor: A randomized controlled study. Neurology, 80(10), 933-940. https://doi.org/10.1212/WNL.0b013e3182840c4f

Octanoic acid in alcohol-responsive essential tremor : A randomized controlled study. / Haubenberger, Dietrich; McCrossin, Gayle; Lungu, Codrin; Considine, Elaine; Toro, Camilo; Nahab, Fatta B.; Auh, Sungyoung; Buchwald, Peter; Grimes, George J.; Starling, Judith; Potti, Gopal; Scheider, Linda; Kalowitz, Daniel; Bowen, Daniel; Carnie, Andrea; Hallett, Mark.

In: Neurology, Vol. 80, No. 10, 05.03.2013, p. 933-940.

Research output: Contribution to journalArticle

Haubenberger, D, McCrossin, G, Lungu, C, Considine, E, Toro, C, Nahab, FB, Auh, S, Buchwald, P, Grimes, GJ, Starling, J, Potti, G, Scheider, L, Kalowitz, D, Bowen, D, Carnie, A & Hallett, M 2013, 'Octanoic acid in alcohol-responsive essential tremor: A randomized controlled study', Neurology, vol. 80, no. 10, pp. 933-940. https://doi.org/10.1212/WNL.0b013e3182840c4f
Haubenberger D, McCrossin G, Lungu C, Considine E, Toro C, Nahab FB et al. Octanoic acid in alcohol-responsive essential tremor: A randomized controlled study. Neurology. 2013 Mar 5;80(10):933-940. https://doi.org/10.1212/WNL.0b013e3182840c4f
Haubenberger, Dietrich ; McCrossin, Gayle ; Lungu, Codrin ; Considine, Elaine ; Toro, Camilo ; Nahab, Fatta B. ; Auh, Sungyoung ; Buchwald, Peter ; Grimes, George J. ; Starling, Judith ; Potti, Gopal ; Scheider, Linda ; Kalowitz, Daniel ; Bowen, Daniel ; Carnie, Andrea ; Hallett, Mark. / Octanoic acid in alcohol-responsive essential tremor : A randomized controlled study. In: Neurology. 2013 ; Vol. 80, No. 10. pp. 933-940.
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AU - Lungu, Codrin

AU - Considine, Elaine

AU - Toro, Camilo

AU - Nahab, Fatta B.

AU - Auh, Sungyoung

AU - Buchwald, Peter

AU - Grimes, George J.

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AU - Potti, Gopal

AU - Scheider, Linda

AU - Kalowitz, Daniel

AU - Bowen, Daniel

AU - Carnie, Andrea

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N2 - Objective: To assess safety and efficacy of an oral, single, low dose of octanoic acid (OA) in subjects with alcohol-responsive essential tremor (ET). Methods: We conducted a double-blind, placebo-controlled, crossover, phase I/II clinical trial evaluating the effect of 4 mg/kg OA in 19 subjects with ET. The primary outcome was accelerometric postural tremor power of the dominant hand 80 minutes after administration. Secondary outcomes included digital spiral analysis, pharmacokinetic sampling, as well as safety measures. Results: OA was safe and well tolerated. Nonserious adverse events were mild (Common Terminology Criteria for Adverse Events grade 1) and equally present after OA and placebo. At the primary outcome, OA effects were not different from placebo. Secondary outcome analyses of digital spiral analysis, comparison across the entire time course in weighted and nonweighted accelerometry, as well as nondominant hand tremor power did not show a benefit of OA over placebo. The analysis of individual time points showed that OA improved tremor at 300 minutes (dominant hand, F1,16 = 5.49, p = 0.032 vs placebo), with a maximum benefit at 180 minutes after OA (both hands, F1,16 = 6.1, p = 0.025). Conclusions: Although the effects of OA and placebo at the primary outcome were not different, secondary outcome measures suggest superiority of OA in reducing tremor at later time points, warranting further trials at higher dose levels. Classification of evidence: This study provides Class I evidence that a single 4-mg/kg dose of OA is not effective in reducing postural tremor in patients with ET at a primary outcome of 80 minutes, but is effective for a secondary outcome after 180 minutes.

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