Cyclic Deep Brain Stimulation in Essential Tremor

Cyclic Versus Continuous Deep Brain Stimulation in Essential Tremor

The aim of the study is to prove the efficacy and safety of cyclical deep brain stimulation (DBS) in patients with essential tremor, and demonstrate non-inferiority of cyclical DBS on tremor control when compared to continuous stimulation.

Study Overview

• Status: Recruiting
• Conditions: Essential Tremor
• Intervention / Treatment: Device: Abbott St Jude Medical Infinity 7 neurostimulator

Detailed Description

This study is a prospective, randomized, double-blind cross-over trials. Patients will be randomized into two groups in a cross-over fashion to have either continuous or cyclical stimulation for a total of three months. Following this, the trial will be unblinded and open-label follow up will continue for another nine months. Device use as per standard practice continues after the end of the trial.

If the hypothesis is proven correct, this will provide proof of concept that cyclical stimulation for the treatment of essential tremor results in improved battery life, reduced number of operations for battery changes, reduction in stimulation side-effects and enhancing quality of life.

• Study Type: Interventional
• Enrollment (Anticipated): 15
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kantharuby Tambirajoo, MD; Phone Number: 00442032991906; Email: kantharuby.tambirajoo@nhs.net

Study Locations

• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Recruiting
    • King's College Hospital NHS Foundation Trust
    • Contact: Kantharuby Tambirajoo, MD; Phone Number: 0044 2032991906; Email: kantharuby.tambirajoo@nhs.net
    • Principal Investigator: Keyoumars Ashkan, MD
    • Sub-Investigator: Kantharuby Tambirajoo, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Participant is at least 18 years of age
2. Participant has confirmed diagnosis of medically-refractory essential tremor
3. Participant meets criteria for implantation of DBS system
4. Participant understands the study requirements and treatments procedures and provides informed consent before any study-specific tests or procedures are performed

Exclusion Criteria:

1. Participant meets any contraindications for implantation of DBS system
2. Participant is undergoing or has had previous thalamic stimulation either in a research trial or with a permanent implant
3. Participant is unwilling or unable to comply with all study required follow-up evaluations

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cyclical Stimulation; This group will undergo cyclical stimulation mode of stimulation	Device: Abbott St Jude Medical Infinity 7 neurostimulator; The stimulator has the capability to deliver both continuous and cyclical modes of stimulation which is being investigated in this study
Active Comparator: Continuous Stimulation; This group will undergo the standard continuous mode of stimulation	Device: Abbott St Jude Medical Infinity 7 neurostimulator; The stimulator has the capability to deliver both continuous and cyclical modes of stimulation which is being investigated in this study

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fahn-Tolosa-Marin Tremor Rating Scale - total score difference	Change in Fahn-Tolosa-Marin tremor rating scale at 6 months compared to baseline. Minimum score is 0 and maximum score is 84. Higher scores indicate worse tremor control	6 months compared to baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
EuroQol five dimensions questionnaire (EQ-5D) difference	The total score of EQ-5D questionnaire at 6 months compared to baseline. Each dimension of the questionnaire has a minimum score of 1 and a maximum score of 5. Higher composite scores indicate increased levels of perceived problems	6 months post activation compared to baseline
Beck's Depression Index questionnaire difference	The total score of Beck's Depression Index questionnaire at 6 months compared to baseline. The minimum score is 0 and maximum score is 63. Higher scores indicate increasing severity of depression	6 months post activation compared to baseline
Quality of Life in Essential Tremor (QUEST) questionnaire difference	The total score of Quality of Life in Essential Tremor questionnaire at 6 months compared to baseline. Minimum score is 0 and maximum score is 120 with higher scores indicating worse quality of life due to tremor	6 months post activation compared to baseline
Satisfaction with Treatment (SWT) questionnaire difference	The difference in Satisfaction with Treatment outcomes at 6 months compared to baseline	6 months post activation compared to baseline
Clinical Global Impression of Change (CGI) difference	The difference in Clinical Global Impression of change outcome at 6 months compared to baseline	6 months post activation compared to baseline
Implantable Pulse Generator (IPG) power consumption and longevity	Total amount of implantable pulse generator consumption used compared between the 2 groups	6 months compared to baseline

Collaborators and Investigators

• Sponsor: King's College Hospital NHS Trust
• Investigators: Principal Investigator: Keyoumars Ashkan, MD, King's College Hospital NHS Trust

Publications and helpful links

General Publications

• Ferreira JJ, Mestre TA, Lyons KE, Benito-Leon J, Tan EK, Abbruzzese G, Hallett M, Haubenberger D, Elble R, Deuschl G; MDS Task Force on Tremor and the MDS Evidence Based Medicine Committee. MDS evidence-based review of treatments for essential tremor. Mov Disord. 2019 Jul;34(7):950-958. doi: 10.1002/mds.27700. Epub 2019 May 2.
• Flora ED, Perera CL, Cameron AL, Maddern GJ. Deep brain stimulation for essential tremor: a systematic review. Mov Disord. 2010 Aug 15;25(11):1550-9. doi: 10.1002/mds.23195.
• Koller WC, Lyons KE, Wilkinson SB, Troster AI, Pahwa R. Long-term safety and efficacy of unilateral deep brain stimulation of the thalamus in essential tremor. Mov Disord. 2001 May;16(3):464-8. doi: 10.1002/mds.1089.
• Rehncrona S, Johnels B, Widner H, Tornqvist AL, Hariz M, Sydow O. Long-term efficacy of thalamic deep brain stimulation for tremor: double-blind assessments. Mov Disord. 2003 Feb;18(2):163-70. doi: 10.1002/mds.10309.
• Wharen RE Jr, Okun MS, Guthrie BL, Uitti RJ, Larson P, Foote K, Walker H, Marshall FJ, Schwalb J, Ford B, Jankovic J, Simpson R, Dashtipour K, Phibbs F, Neimat JS, Stewart RM, Peichel D, Pahwa R, Ostrem JL; SJM DBS ET Study Group. Thalamic DBS with a constant-current device in essential tremor: A controlled clinical trial. Parkinsonism Relat Disord. 2017 Jul;40:18-26. doi: 10.1016/j.parkreldis.2017.03.017. Epub 2017 Mar 30.
• Paschen S, Forstenpointner J, Becktepe J, Heinzel S, Hellriegel H, Witt K, Helmers AK, Deuschl G. Long-term efficacy of deep brain stimulation for essential tremor: An observer-blinded study. Neurology. 2019 Mar 19;92(12):e1378-e1386. doi: 10.1212/WNL.0000000000007134. Epub 2019 Feb 20.
• Hariz GM, Blomstedt P, Koskinen LO. Long-term effect of deep brain stimulation for essential tremor on activities of daily living and health-related quality of life. Acta Neurol Scand. 2008 Dec;118(6):387-94. doi: 10.1111/j.1600-0404.2008.01065.x. Epub 2008 Jul 8.
• Troster AI, Pahwa R, Fields JA, Tanner CM, Lyons KE. Quality of life in Essential Tremor Questionnaire (QUEST): development and initial validation. Parkinsonism Relat Disord. 2005 Sep;11(6):367-73. doi: 10.1016/j.parkreldis.2005.05.009.

Study record dates

Study Major Dates

• Study Start (Actual): February 25, 2020
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2022

Study Registration Dates

• First Submitted: February 6, 2020
• First Submitted That Met QC Criteria: February 6, 2020
• First Posted (Actual): February 7, 2020

Study Record Updates

• Last Update Posted (Actual): September 2, 2021
• Last Update Submitted That Met QC Criteria: September 1, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Essential Tremor; Deep Brain Stimulation
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Tremor; Essential Tremor
• Other Study ID Numbers: KCH20-025; 270731 (Other Identifier: Integrated Research Application System (IRAS))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No