Essential Tremor (ET)
Conditions
Keywords
Essential tremor, Deep brain stimulation, Posterior subthalamic area, Ventral intermediate nucleus
Brief summary
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.
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.
Interventions
Bilateral implantation of octopolar DBS leads covering VIM and PSA
Sponsors
Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental
Carlos III Health Institute
European Regional Development Fund
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in tremor assessed by Fahn-Tolosa-Marin Tremor Rating Scale (FTM-TRS) total score | - Preoperative baseline, - 4 postoperative months (after the first 3-month stimulation period) and - 7 postoperative months (after the second 3-month stimulation period) | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Stimulation efficiency assessed by stimulation amplitudes (mA) | 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 stimulation amplitudes (mA). The greater the amplitude, the higher the energy consumption (lower theoretical energy efficiency) |
| Stimulation efficiency measured by total electrical energy delivered (TEED) | 4 postoperative months (after the first 3-month stimulation period) and 7 postoperative months (after the second 3-month stimulation period) | 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. |
| Quality of life (QoL) assessed using Visual Analog Scale (VAS) | - Preoperative baseline, - 4 postoperative months (after the first 3-month stimulation period) and - 7 postoperative months (after the second 3-month stimulation period) | 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) |
| Quality of life (QoL) assessed using the Quality of life in essential tremor questionnaire (QUEST) | - Preoperative baseline, - 4 postoperative months (after the first 3-month stimulation period) and - 7 postoperative months (after the second 3-month stimulation period) | 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) |
| Number and type of stimulation-induced side effects | - 4 postoperative months (after the first 3-month stimulation period) and - 7 postoperative months (after the second 3-month stimulation period) | Type and frequency (absolute and relative) of stimulation-induced side effects in the VIM-DBS vs PSA-DBS period |
| Overall cognitive assessment evaluated using the Dementia Rating Scale 2 (DRS-2) | - Preoperative baseline, - 4 postoperative months (after the first 3-month stimulation period) and - 7 postoperative months (after the second 3-month stimulation period) | 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) |
Countries
Spain
Contacts
PRINCIPAL_INVESTIGATORMajed 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_INVESTIGATORFrancisco Escamilla Sevilla
Department of Neurology, Virgen de las Nieves University Hospital (Granada, Spain)
Outcome results
None listed