Deep braIn Stimulation for Tremor TractographIC Versus Traditional

Study Overview
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Brief Summary
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This is a monocentric, randomized, controlled, 2 arms, interventional, observer-blinded feasibility trial. Patients suffering from essential tremor (ET) will be treated with Deep Brain Stimulation (DBS). For the implantation of the DBS electrodes and the DBS system (Activa INS, Medtronic) patients will randomized either to conventional stereotactic surgery of thalamic/subthalamic region with short anesthesia or to MR-tractography guided stereotactic surgery with target point of the dentato-rubro-thalamic bundle (DRT) in general anesthesia. Patients will visit the study center at screening, baseline/neurosurgery, six and twelve months after neurosurgery.

Detailed Description
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In this monocentric, randomized, controlled, 2 arms, interventional, observer-blinded feasibility trial patients suffering from therapy resistant essential tremor (ET) will be treated with Deep Brain Stimulation (DBS). After screening (e.g. obtaining informed consent, assessment of inclusion/exclusion criteria etc.) patients will be randomized to one of the following groups: Group 1 (conventional): Conventional AC-PC based DBS implantation in the thalamic/subthalamic region (Vim-cZI) starting as awake surgery with a brief general anesthesia for stimulator implantation at the end of surgery. Group 2 (tractographic): Magnetic resonance (MR)-tractography guided DBS implantation in the dentato-rubro-thalamic bundle (DRT) in general anesthesia At the baseline/neurosurgery visit Quality of Life (QoL) and other parameters will assessed. Medtronic's Activa INS DBS will be implanted according to randomization. DBS will be started approximately one month after surgery and will be applied as per routine. Patients will have their routine visits. For this trial data of the (routine) visits six and twelve months after neurosurgery will be collected. Patients receive DBS after the end of the trial according to local standards.

Official Title
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Deep braIn Stimulation for Tremor TractographIC Versus Traditional

Conditions
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Essential Tremor

Intervention / Treatment
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* Device: Conventional AC-PC based implantation of ACTIVA INS DBS system
* Device: MR-tractography guided implantation of ACTIVA INS DBS system


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female patients aged ≥ 25 and ≤ 80 years Patients with Essential Tremor according to the criteria of the consensus statement of the movement disorders society (Deuschl et al. 1998) are included with a medical treatment resistant and disabling postural and/or intentional tremor. FTMTRS to be completed within 42 days prior surgery Stable tremor medication for at least 3 months prior inclusion Written informed consent Exclusion Criteria: Major Depression with suicidal thoughts or suicidal thoughts in history Dementia (Mattis Dementia Rating Score ≤ 130) Acute psychosis Patient incapability Nursing care at home Surgical contraindications Medications that are likely to cause interactions in the opinion of the investigator Known or persistent abuse of medication, drugs or alcohol Persons who are in a relationship of dependence/employment with the sponsor or the investigator Fertile women not using adequate contraceptive methods: female condoms, diaphragm or coil, each used in combination with spermicides; intra-uterine device; hormonal contraception in combination with a mechanical method of contraception; Current or planned pregnancy, nursing period

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Conventional AC-PC based implantation of ACTIVA INS DBS system<br>Conventional AC-PC based DBS implantation in the thalamic/subthalamic region (Vim-cZI) starting as awake surgery with a brief general anesthesia for stimulator implantation at the end of surgery. | Device: Conventional AC-PC based implantation of ACTIVA INS DBS system<br>* Conventional AC-PC based implantation of ACTIVA INS DBS system (manufactured by Medtronic) in the thalamic/subthalamic region (Vim-cZI).<br>* Other names: Medtronic ACTIVA INS Deep Brain Stimulation system;|
| Experimental: MR-tractography guided implantation of ACTIVA INS DBS system<br>MR-tractography guided DBS implantation in the dentato-rubro-thalamic bundle (DRT) in general anesthesia. | Device: MR-tractography guided implantation of ACTIVA INS DBS system<br>* MR-tractography guided implantation of ACTIVA INS DBS system (manufactured by Medtronic) in the DRT.<br>* Other names: Medtronic ACTIVA INS Deep Brain Stimulation system;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tremor reduction defined by the difference in FTMTRS at 6 months after intervention to baseline | Tremor reduction defined by the difference in Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) at 6 months after intervention to baseline | Baseline, 6 months after neurosurgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Effective tremor reduction at 12 months after intervention | Effective tremor reduction (an FTMTRS score reduction by 50% compared to baseline is regarded as response) at 12 months after intervention | Baseline, 12 months after neurosurgery | 
| Tremor reduction measured by tremor analysis at baseline and 6 and 12 months after intervention | Tremor reduction will be measured by tremor analysis (an accelerometric examination); Unit: Hertz (Hz) | Baseline, 6 and 12 months after neurosurgery | 
| Tremor reduction measured by calculation of total power at baseline and 6 and 12 months after intervention | Tremor reduction will be assessed during Electromyography (EMG) by the calculation of total power; Unit: mg², with g=9,81 m/s² | Baseline, 6 and 12 months after neurosurgery | 
| Quality of Life: QUEST, SF-36 | Quality of Life assessed by Quality of Life Essential Tremor Questionnaire (QUEST) and Short Form (36) Health Survey | Baseline, 6 and 12 months after neurosurgery | 
| Size of VAT | Size of Volume of activated tissue (VAT) | Day 0 (Day of neurosurgery) | 
| Effective contact position with respect to DRT and AC-PC coordinates | Effective contact position of stimulation electrodes (with respect to the Dentato-rubro-thalamic bundle (DRT) and anterior commissure (AC) - posterior commissure (PC) line (ACPC) coordinates) | Day 0 (Day of neurosurgery) | 
| Duration of neurosurgery | Duration of neurosurgery (time points of mounting frame, start surgery, stop surgery (= dismounting frame) | Day 0 (Day of neurosurgery) | 
| Changes in BDI | Psychiatric assessment: changes in Beck's Depression Inventory (BDI) | Baseline, 6 and 12 months after neurosurgery | 
| Assessment of (Serious) Adverse Events related to intervention |  | Up to 12 months after neurosurgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deep Brain Stimulation, Essential tremor, DISTINCT, MR-tractography guided DBS implantation, Conventional AC-PC based DBS implantation