Clinical Trial to Compare VIM vs PSA Bilateral Deep Brain Stimulation in Patients With Essential Tremor

Randomised, Double-Blind, Crossover Clinical Trial Comparing Bilateral Deep Brain Stimulation of the Posterior Subthalamic Area Versus the Ventral Intermediate Nucleus of the Thalamus in Essential Tremor

Deep brain stimulation (DBS) of both ventral intermediate nucleus (VIM) and the posterior subthalamic area (PSA) has shown to be an effective treatment for essential tremor (ET). Characterizing the differences between both targets is necessary. The aim of the study is comparison of efficacy, safety, energy efficiency, neuropsychological status and quality of life of bilateral PSA-DBS vs bilateral VIM-DBS in the treatment of ET. The study hypothesis is that PSA-DBS is not inferior to VIM-DBS in terms of efficacy in controlling tremor, but has superior energy efficiency and safety.

Study Overview

• Status: Completed
• Conditions: Essential Tremor (ET)
• Intervention / Treatment: Device: Deep Brain Stimulation (DBS)

Detailed Description

Deep brain stimulation (DBS) of the ventral intermediate (VIM) nucleus of the thalamus is an effective treatment for disabling essential tremor (ET). In recent years, the posterior subthalamic area (PSA) has emerged as a potentially more effective target. There is a need for specific research into the clinical efficacy, efficiency, as well as the mid-term cognitive and quality-of-life outcomes of VIM-DBS and PSA-DBS. The aim of this study is: 1) to compare the efficacy and safety of bilateral PSA-DBS versus bilateral VIM-DBS in the treatment of ET. 2) to determine the impact of bilateral PSA-DBS versus bilateral VIM-DBS on quality of life, neuropsychological status, energy efficiency of the DBS system, and durability of the tremor-suppressing effect. The hypothesis is that PSA-DBS is not inferior to VIM-DBS in terms of efficacy in controlling tremor, but has superior energy efficiency and safety. To this end, a randomized, double-blind, crossover trial will be conducted, in which bilateral octopolar DBS leads will be implanted in a single-trajectory covering the VIM and PSA in patients with disabling and refractory ET. They will be randomly assigned to group 1 (PSA-VIM) or group 2 (VIM-PSA), undergoing stimulation on each target for 3 months. A blinded assessment will be carried out at the end of each period.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Granada
    • Granada, Granada, Spain, 18013
      • Virgen de las Nieves University Hospital (Neurotraumatology and Rehabilitation Hospital)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Confirmed diagnosis of bilateral ET or ET-plus according to the Movement Disorders Society criteria.
• Refractoriness to medication: at least two attempts at medical treatment with at least two groups of different medication (fundamentally propranolol and primidone), which were ineffective (insufficient tremor control or adverse effects).
• Subjects of both sexes, older than 18 years old.
• Sufficient competence to collaborate and comply with the study protocols.
• Ability to provide informed consent.

Exclusion Criteria:

• Clinically relevant cognitive decline which may interfere with the study.
• Clinically relevant active psychiatric disorder.
• Contraindication for general surgery or bilateral DBS.
• Unsuitable electrode location according to neuroimaging.
• Participation in other interventional study.
• Cerebral atrophy (width of the third ventricle >10 mm) or other anatomical anomalies that would interfere with optimal stereotactic localization.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: VIM-DBS; Stimulation delivered to VIM	Device: Deep Brain Stimulation (DBS); Bilateral implantation of octopolar DBS leads covering VIM and PSA
Experimental: PSA-DBS; Stimulation delivered to PSA	Device: Deep Brain Stimulation (DBS); Bilateral implantation of octopolar DBS leads covering VIM and PSA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Improvement in tremor assessed by Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) total score	Improvement from baseline to the end of the VIM-DBS vs PSA-DBS period, assessed as the FTM-TRS total score (0-144 points; higher scores indicate greater tremor severity).	- Preoperative baseline, - 4 postoperative months (after the first 3-month stimulation period) and - 7 postoperative months (after the second 3-month stimulation period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stimulation efficiency assessed by stimulation amplitudes (mA)	Stimulation efficiency measured by stimulation amplitudes (mA). The greater the amplitude, the higher the energy consumption (lower theoretical energy efficiency)	4 postoperative months (after the first 3-month stimulation period) and 7 postoperative months (after the second 3-month stimulation period)
Stimulation efficiency measured by total electrical energy delivered (TEED)	TEED (μJ) = [(I² · R · PW · f) 1e-6], where DBS parameters are frequency (f, Hz), pulse width (PW, μsec), impedance (R, Ω) and current intensity (I, mA). The higher the TEED, the lower the energy efficiency.	4 postoperative months (after the first 3-month stimulation period) and 7 postoperative months (after the second 3-month stimulation period)
Quality of life (QoL) assessed using Visual Analog Scale (VAS)	Change from baseline to the end of the VIM-DBS vs PSA-DBS period assessed using VAS-QoL (1-10; higher scores indicate better QoL)	- Preoperative baseline, - 4 postoperative months (after the first 3-month stimulation period) and - 7 postoperative months (after the second 3-month stimulation period)
Quality of life (QoL) assessed using the Quality of life in essential tremor questionnaire (QUEST)	Change from baseline to the end of the VIM-DBS vs PSA-DBS period assessed using the QUEST (1-120; higher scores indicate poor QoL)	- Preoperative baseline, - 4 postoperative months (after the first 3-month stimulation period) and - 7 postoperative months (after the second 3-month stimulation period)
Number and type of stimulation-induced side effects	Type and frequency (absolute and relative) of stimulation-induced side effects in the VIM-DBS vs PSA-DBS period	- 4 postoperative months (after the first 3-month stimulation period) and - 7 postoperative months (after the second 3-month stimulation period)
Overall cognitive assessment evaluated using the Dementia Rating Scale 2 (DRS-2)	Change in cognition from baseline to the end of the VIM-DBS vs PSA-DBS period assessed using the DRS-2 (1-144; higher scores indicate better cognitive performance)	- Preoperative baseline, - 4 postoperative months (after the first 3-month stimulation period) and - 7 postoperative months (after the second 3-month stimulation period)

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental
• Collaborators: Carlos III Health Institute; European Regional Development Fund
• Investigators: Principal Investigator: Majed Jouma Katati, PhD, Department of Surgery, Faculty of Medicine, Granada University (Granada, Spain). Department of Neurosurgery, Virgen de las Nieves University Hospital (Granada, Spain); Principal Investigator: Francisco Escamilla Sevilla, Department of Neurology, Virgen de las Nieves University Hospital (Granada, Spain)

Publications and helpful links

General Publications

• Barbe MT, Reker P, Hamacher S, Franklin J, Kraus D, Dembek TA, Becker J, Steffen JK, Allert N, Wirths J, Dafsari HS, Voges J, Fink GR, Visser-Vandewalle V, Timmermann L. DBS of the PSA and the VIM in essential tremor: A randomized, double-blind, crossover trial. Neurology. 2018 Aug 7;91(6):e543-e550. doi: 10.1212/WNL.0000000000005956. Epub 2018 Jul 3.

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2020
• Primary Completion (Actual): December 20, 2023
• Study Completion (Actual): July 24, 2024

Study Registration Dates

• First Submitted: March 20, 2026
• First Submitted That Met QC Criteria: April 7, 2026
• First Posted (Actual): April 13, 2026

Study Record Updates

• Last Update Posted (Actual): April 13, 2026
• Last Update Submitted That Met QC Criteria: April 7, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Essential tremor; Deep brain stimulation; Posterior subthalamic area; Ventral intermediate nucleus
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Essential Tremor; Therapeutics; Surgical Procedures, Operative; Electric Stimulation Therapy; Deep Brain Stimulation
• Other Study ID Numbers: PI19/01571

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The data are not publicly available due to the risk of breached patient confidentiality

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No