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Citations to this article

Dose-escalation study of octanoic acid in patients with essential tremor
Bernhard Voller, … , Dietrich Haubenberger, Mark Hallett
Bernhard Voller, … , Dietrich Haubenberger, Mark Hallett
Published February 29, 2016
Citation Information: J Clin Invest. 2016;126(4):1451-1457. https://doi.org/10.1172/JCI83621.
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Clinical Research and Public Health Neuroscience Article has an altmetric score of 13

Dose-escalation study of octanoic acid in patients with essential tremor

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Abstract

BACKGROUND. Recently, 1-octanol has been shown to have efficacy in treating patients with essential tremor (ET). The primary metabolite of 1-octanol is octanoic acid (OA), which is now thought to be the active substance that mediates tremor suppression. Our aim was to describe the maximum tolerated dose (MTD) of oral OA in patients with ET and assess the pharmacokinetics (PK) and pharmacodynamics (PD) profile of OA.

METHODS. The MTD was studied using an open-label, single-ascending 3 + 3 dose–escalation design. Predefined single doses ranged from 8 to 128 mg/kg, with grade 2 adverse events (AEs) defined as dose-limiting toxicity. Tremor was assessed using accelerometry, digital spiral analysis, and a standard clinical rating scale at baseline and up to 600 minutes after intake. Safety assessments and PK sampling were also performed.

RESULTS. Dose-limiting toxicity was not reached. The most frequent AE was mild abdominal discomfort. Exposure (AUC) increased linearly with the dose. Secondary efficacy measures suggested a dose-dependent reduction of tremor. Accordingly, a single unified PK/PD model with an effect compartment and sigmoid maximum effect (Emax) response could be built that accounted well for the time profiles of plasma concentrations as well as effects on tremor severity across the 5 dose levels.

CONCLUSION. Although our trial did not reach an MTD, a dose-dependent effect was demonstrated in the PK/PD model as well as in secondary efficacy outcomes. Future studies are needed to explore the safety in higher dose ranges and to confirm dose-dependent efficacy in a placebo-controlled design.

TRIAL REGISTRATION. Clinicaltrials.gov NCT01468948

FUNDING. NINDS Intramural Research Program; TG Therapeutics Inc.

Authors

Bernhard Voller, Emily Lines, Gayle McCrossin, Sule Tinaz, Codrin Lungu, George Grimes, Judith Starling, Gopal Potti, Peter Buchwald, Dietrich Haubenberger, Mark Hallett

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Total citations by year

Year: 2024 2023 2021 2020 2018 2017 Total
Citations: 3 1 1 4 2 1 12
Citation information
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Citations to this article (12)

Title and authors Publication Year
Octanoic acid mitigates busulfan-induced blood-testis barrier damage by alleviating oxidative stress and autophagy
Cao C, Zhang H, He Z, Zhang K, Qian Z, Shen J, Zheng L, Xue M, Sun S, Li C, Zhao W, Jing J, Ma R, Ge X, Yao B
Lipids in Health and Disease 2024
Tips and tricks in tremor treatment.
Hopfner F, Buhmann C, Classen J, Holtbernd F, Klebe S, Koschel J, Kohl Z, Paus S, Pedrosa DJ
Journal of neural transmission (Vienna, Austria : 1996) 2024
Postmortem Fatty Acid Abnormalities in the Cerebellum of Patients with Essential Tremor.
Simard M, Mélançon K, Berthiaume L, Tremblay C, Pshevorskiy L, Julien P, Rajput AH, Rajput A, Calon F
Cerebellum (London, England) 2024
T‐type calcium channels as therapeutic targets in essential tremor and Parkinson's disease
Matthews LG, Puryear CB, Correia SS, Srinivasan S, Belfort GM, Pan M, Kuo S
Annals of Clinical and Translational Neurology 2023
Essential tremor
T Welton, F Cardoso, JA Carr, LL Chan, G Deuschl, J Jankovic, EK Tan
Nature Reviews Disease Primers 2021
Mechanisms and Pharmacotherapy for Ethanol-Responsive Movement Disorders
J Wu, H Tang, S Chen, L Cao
Frontiers in neurology 2020
Current and Future Neuropharmacological Options for the Treatment of Essential Tremor
H Alonso-Navarro, E García-Martín, JA Agúndez, FJ Jiménez-Jiménez
Current neuropharmacology 2020
Effect of Gold Electronic State on the Catalytic Performance of Nano Gold Catalysts in n-Octanol Oxidation
E Pakrieva, E Kolobova, Y Kotolevich, L Pascual, SA Carabineiro, AN Kharlanov, D Pichugina, N Nikitina, D German, TA Partida, HJ Vazquez, MH Farías, N Bogdanchikova, VC Corberán, A Pestryakov
Nanomaterials 2020
Local Vibrational Therapy for Essential Tremor Reduction: A Clinical Study
S Abramavičius, M Venslauskas, A Vaitkus, V Gudžiūnas, O Laucius, E Stankevičius
MED LITH 2020
The response of the central and peripheral tremor component to octanoic acid in patients with essential tremor
H Cao, J Thompson-Westra, M Hallett, D Haubenberger
Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology 2018
The Effect of Octanoic Acid on Essential Voice Tremor: A Double-Blind, Placebo-Controlled Study: Effect of Octanoic Acid on EVT
SY Lowell, RT Kelley, M Monahan, CJ Hosbach-Cannon, RH Colton, D Mihaila
The Laryngoscope 2018
Emerging strategies in the management of essential tremor
P Hedera
Therapeutic advances in neurological disorders 2017

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