Variable- versus constant-frequency deep-brain stimulation in patients with advanced Parkinson's disease: study protocol for a randomized controlled trial

Fumin Jia, Jianguo Zhang, Huimin Wang, Zhanhua Liang, Weiguo Liu, Xuelian Wang, Yiming Liu, Yi Guo, Zhipei Ling, Xiaodong Cai, Xi Wu, Jianjun Wu, Wen Lv, Xin Xu, Wenbin Zhang, Luming Li, Fumin Jia, Jianguo Zhang, Huimin Wang, Zhanhua Liang, Weiguo Liu, Xuelian Wang, Yiming Liu, Yi Guo, Zhipei Ling, Xiaodong Cai, Xi Wu, Jianjun Wu, Wen Lv, Xin Xu, Wenbin Zhang, Luming Li

Abstract

Background: Deep-brain stimulation targeting the subthalamic nucleus (STN) can be used to treat motor symptoms and dyskinesia in the advanced stages of Parkinson's disease (PD). High-frequency stimulation (HFS) of the STN can lead to consistent, long-term improvement of PD symptoms. However, the effects of HFS on the axial symptoms of PD, specifically freezing of gait, can be limited or cause further impairment. While this can be alleviated via relatively low-frequency stimulation (LFS) in selected patients, LFS does not control all motor symptoms of PD. Recently, the National Engineering Laboratory for Neuromodulation reported preliminary findings regarding an efficient way to combine the advantages of HFS and LFS to form variable-frequency stimulation (VFS). However, this novel therapeutic strategy has not been formally tested in a randomized trial.

Methods/design: We propose a multicenter, double-blind clinical trial involving 11 study hospitals and an established deep-brain stimulation team. The participants will be divided into a VFS and a constant-frequency stimulation group. The primary outcome will be changes in stand-walk-sit task scores after 3 months of treatment in the "medication off" condition. Secondary outcome measures include specific item scores on the Freezing of Gait Questionnaire and quality of life. The aim of this trial is to investigate the efficacy and safety of VFS compared with constant-frequency stimulation.

Discussion: This is the first randomized controlled trial to comprehensively evaluate the effectiveness and safety of VFS of the STN in patients with advanced PD. VFS may represent a new option for clinical treatment of PD in the future.

Trial registration: ClinicalTrials.gov, NCT03053726. Registered on February 15, 2017.

Keywords: Deep-brain stimulation; Parkinson’s disease; Subthalamic nucleus; Variable frequency stimulation.

Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Flow chart of the RESTEP trial

References

    1. Fasano A, Aquino CC, Krauss JK, Honey CR, Bloem BR. Axial disability and deep brain stimulation in patients with Parkinson disease. Nat Rev Neurol. 2015;11(2):98–110. doi: 10.1038/nrneurol.2014.252.
    1. Fahn S. The freezing phenomenon in parkinsonism. Adv Neurol. 1995;67:53–63.
    1. Shine JM, Naismith SL, Lewis SJ. The pathophysiological mechanisms underlying freezing of gait in Parkinson's disease. J Clin Neurosci. 2011;18(9):1154–1157. doi: 10.1016/j.jocn.2011.02.007.
    1. Nutt JG, Bloem BR, Giladi N, Hallett M, Horak FB, Nieuwboer A. Freezing of gait: moving forward on a mysterious clinical phenomenon. Lancet Neurol. 2011;10(8):734–744. doi: 10.1016/S1474-4422(11)70143-0.
    1. Benabid AL, Chabardes S, Mitrofanis J, Pollak P. Deep brain stimulation of the subthalamic nucleus for the treatment of Parkinson's disease. Lancet Neurol. 2009;8(1):67–81. doi: 10.1016/S1474-4422(08)70291-6.
    1. Sidiropoulos C. Low-frequency stimulation of STN-DBS reduces aspiration and freezing of gait in patients with PD. Neurology. 2015;85(6):557. doi: 10.1212/WNL.0000000000001823.
    1. Zibetti M, Moro E, Krishna V, Sammartino F, Picillo M, Munhoz RP, et al. Low-frequency subthalamic stimulation in Parkinson's disease: long-term outcome and predictors. Brain Stimul. 2016;9(5):774–779. doi: 10.1016/j.brs.2016.04.017.
    1. Jia F, Guo Y, Wan S, et al. Variable frequency stimulation of subthalamic nucleus for freezing of gait in Parkinson's disease. Parkinsonism Relat Disord. 2015;21(12):1471–1472. doi: 10.1016/j.parkreldis.2015.10.002.
    1. Weiss D, Walach M, Meisner C, Fritz M, Scholten M, Breit S, et al. Nigral stimulation for resistant axial motor impairment in Parkinson's disease? A randomized controlled trial. Brain. 2013;136(7):2098–2108. doi: 10.1093/brain/awt122.
    1. Weiss D, Breit S, Wächter T, Plewnia C, Gharabaghi A, Krüger R. Combined stimulation of the substantia nigra pars reticulata and the subthalamic nucleus is effective in hypokinetic gait disturbance in Parkinson's disease. J Neurol. 2011;258(6):1183–1185. doi: 10.1007/s00415-011-5906-3.
    1. Vallabhajosula S, Haq IU, Hwynn N, Oyama G, Okun M, Tillman MD, et al. Low-frequency versus high-frequency subthalamic nucleus deep brain stimulation on postural control and gait in Parkinson's disease: a quantitative study. Brain Stimul. 2015;8(1):64–75. doi: 10.1016/j.brs.2014.10.011.
    1. Sidiropoulos C, Walsh R, Meaney C, Poon YY, Fallis M, Moro E. Low-frequency subthalamic nucleus deep brain stimulation for axial symptoms in advanced Parkinson's disease. J Neurol. 2013;260(9):2306–2311. doi: 10.1007/s00415-013-6983-2.

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