Deep braIn Stimulation for Tremor TractographIC Versus Traditional

Not Applicable

• Conditions: Essential Tremor
• Interventions: Device: Conventional AC-PC based implantation of ACTIVA INS DBS system; Device: MR-tractography guided implantation of ACTIVA INS DBS system

• Registration Number: NCT02491554
• Lead Sponsor: University Hospital Freiburg

Brief Summary

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

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.

Study Timeline

• Study First Submitted: 2015-06-30
• Study First Submitted QC: 2015-07-02
• Study First Posted: 2015-07-08
• Study Start: 2015-08
• Status Verified: 2021-07
• Last Update Submitted: 2021-07-20
• Last Update Posted: 2021-07-28
• Primary Completion: 2021-10-31
• Study Completion: 2022-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Male or female patients aged ≥ 25 and ≤ 80 years
2. 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.
3. FTMTRS to be completed within 42 days prior surgery
4. Stable tremor medication for at least 3 months prior inclusion
5. Written informed consent

Exclusion Criteria

1. Major Depression with suicidal thoughts or suicidal thoughts in history
2. Dementia (Mattis Dementia Rating Score ≤ 130)
3. Acute psychosis
4. Patient incapability
5. Nursing care at home
6. Surgical contraindications
7. Medications that are likely to cause interactions in the opinion of the investigator
8. Known or persistent abuse of medication, drugs or alcohol
9. Persons who are in a relationship of dependence/employment with the sponsor or the investigator
10. 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;
11. Current or planned pregnancy, nursing period

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Conventional AC-PC based implantation of ACTIVA INS DBS system	Conventional AC-PC based implantation of ACTIVA INS DBS system	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.
MR-tractography guided implantation of ACTIVA INS DBS system	MR-tractography guided implantation of ACTIVA INS DBS system	MR-tractography guided DBS implantation in the dentato-rubro-thalamic bundle (DRT) in general anesthesia.

Primary Outcome Measures

Name	Time	Method
Tremor reduction defined by the difference in FTMTRS at 6 months after intervention to baseline	Baseline, 6 months after neurosurgery	Tremor reduction defined by the difference in Fahn-Tolosa-Marin Tremor Rating Scale (FTMTRS) at 6 months after intervention to baseline

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Freiburg - Medical Center - Dept. of Stereotactic and Functional Neurosurgery; 🇩🇪 Freiburg, Germany