Deep braIn Stimulation for Tremor TractographIC Versus Traditional

Essential Tremor Clinical Trial

— DISTINCT  

Official title:

Deep braIn Stimulation for Tremor TractographIC Versus Traditional

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02491554
• Other study ID #: P000847
• Secondary ID: DRKS00008913
• Status: Recruiting
• Phase: N/A
• Start date: August 2015
• Est. completion date: June 30, 2022

Study information

• Verified date: July 2021
• Source: University Hospital Freiburg
• Contact: Volker A Coenen, MD
• Phone: +49 761 270
• Email: stereotaxie[@]uniklinik-freiburg.de
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 24
• Est. completion date: June 30, 2022
• Est. primary completion date: October 31, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Essential Tremor
• Tremor

Intervention

Device:
• Conventional AC-PC based implantation of ACTIVA INS DBS system
Conventional AC-PC based implantation of ACTIVA INS DBS system (manufactured by Medtronic) in the thalamic/subthalamic region (Vim-cZI).
• MR-tractography guided implantation of ACTIVA INS DBS system
MR-tractography guided implantation of ACTIVA INS DBS system (manufactured by Medtronic) in the DRT.

Locations

Country	Name	City	State
Germany	University of Freiburg - Medical Center - Dept. of Stereotactic and Functional Neurosurgery	Freiburg

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital Freiburg	Medtronic Neuromodulation Europe

Country where clinical trial is conducted

Germany, 

References & Publications (11)

Benabid AL, Pollak P, Gao D, Hoffmann D, Limousin P, Gay E, Payen I, Benazzouz A. Chronic electrical stimulation of the ventralis intermedius nucleus of the thalamus as a treatment of movement disorders. J Neurosurg. 1996 Feb;84(2):203-14. — View Citation

Chopra A, Klassen BT, Stead M. Current clinical application of deep-brain stimulation for essential tremor. Neuropsychiatr Dis Treat. 2013;9:1859-65. doi: 10.2147/NDT.S32342. Epub 2013 Dec 2. Review. — View Citation

Coenen VA, Allert N, Mädler B. A role of diffusion tensor imaging fiber tracking in deep brain stimulation surgery: DBS of the dentato-rubro-thalamic tract (drt) for the treatment of therapy-refractory tremor. Acta Neurochir (Wien). 2011 Aug;153(8):1579-85; discussion 1585. doi: 10.1007/s00701-011-1036-z. Epub 2011 May 8. — View Citation

Coenen VA, Allert N, Paus S, Kronenbürger M, Urbach H, Mädler B. Modulation of the cerebello-thalamo-cortical network in thalamic deep brain stimulation for tremor: a diffusion tensor imaging study. Neurosurgery. 2014 Dec;75(6):657-69; discussion 669-70. doi: 10.1227/NEU.0000000000000540. — View Citation

Coenen VA, Mädler B, Schiffbauer H, Urbach H, Allert N. Individual fiber anatomy of the subthalamic region revealed with diffusion tensor imaging: a concept to identify the deep brain stimulation target for tremor suppression. Neurosurgery. 2011 Apr;68(4):1069-75; discussion 1075-6. doi: 10.1227/NEU.0b013e31820a1a20. Erratum in: Neurosurgery. 2011 Jun;68(6):E1780-1. — View Citation

Deistung A, Schäfer A, Schweser F, Biedermann U, Turner R, Reichenbach JR. Toward in vivo histology: a comparison of quantitative susceptibility mapping (QSM) with magnitude-, phase-, and R2*-imaging at ultra-high magnetic field strength. Neuroimage. 2013 Jan 15;65:299-314. doi: 10.1016/j.neuroimage.2012.09.055. Epub 2012 Oct 2. — View Citation

Klein JC, Barbe MT, Seifried C, Baudrexel S, Runge M, Maarouf M, Gasser T, Hattingen E, Liebig T, Deichmann R, Timmermann L, Weise L, Hilker R. The tremor network targeted by successful VIM deep brain stimulation in humans. Neurology. 2012 Mar 13;78(11):787-95. doi: 10.1212/WNL.0b013e318249f702. Epub 2012 Feb 29. — View Citation

Koller W, Biary N, Cone S. Disability in essential tremor: effect of treatment. Neurology. 1986 Jul;36(7):1001-4. — View Citation

Lemaire JJ, Sakka L, Ouchchane L, Caire F, Gabrillargues J, Bonny JM. Anatomy of the human thalamus based on spontaneous contrast and microscopic voxels in high-field magnetic resonance imaging. Neurosurgery. 2010 Mar;66(3 Suppl Operative):161-72. doi: 10.1227/01.NEU.0000365617.41061.A3. — View Citation

Torres CV, Manzanares R, Sola RG. Integrating diffusion tensor imaging-based tractography into deep brain stimulation surgery: a review of the literature. Stereotact Funct Neurosurg. 2014;92(5):282-90. doi: 10.1159/000362937. Epub 2014 Sep 18. Review. — View Citation

Zappia M, Albanese A, Bruno E, Colosimo C, Filippini G, Martinelli P, Nicoletti A, Quattrocchi G, Abbruzzese G, Berardelli A, Allegra R, Aniello MS, Elia AE, Martino D, Murgia D, Picillo M, Squintani G. Treatment of essential tremor: a systematic review of evidence and recommendations from the Italian Movement Disorders Association. J Neurol. 2013 Mar;260(3):714-40. doi: 10.1007/s00415-012-6628-x. Epub 2012 Aug 11. Review. Erratum in: J Neurol. 2013 Mar;260(3):741. Abbruzzese, Giovanni [added]; Berardelli, Alfredo [added]; Allegra, Roberta [added]; Aniello, Maria Stella [added]; Elia, Antonio E [added]; Martino, Davide [added]; Murgia, Daniela [added]; Picillo, Marina [added]; Squintani, Giovanna [added]. — View Citation

* Note: There are 11 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Size of VAT	Size of Volume of activated tissue (VAT)	Day 0 (Day of neurosurgery)
Secondary	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)
Secondary	Duration of neurosurgery	Duration of neurosurgery (time points of mounting frame, start surgery, stop surgery (= dismounting frame)	Day 0 (Day of neurosurgery)
Secondary	Changes in BDI	Psychiatric assessment: changes in Beck's Depression Inventory (BDI)	Baseline, 6 and 12 months after neurosurgery
Secondary	Assessment of (Serious) Adverse Events related to intervention		Up to 12 months after neurosurgery