Multicentre RCT of Awake Versus Asleep Tractography Based DBS for ET

NCT05968976 | Recruiting DMC

• 1 other identifier: NL80368.018.23
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: Deep brain stimulation (DBS) of the thalamus is an effective surgical treatment for patients with disabling essential tremor, despite optimal pharmacological treatment. To date, the standard DBS procedure is performed under local anesthesia which is very burdensome for patients. It is now possible to directly visualize the target (motor) area in the thalamus due to advances in modern imaging techniques. DBS surgery could be performed under general anesthesia (asleep). Objective: The primary objective of the study is to determine whether asleep thalamic DBS surgery provides an equal tremor reduction compared to awake thalamic DBS surgery, measured by the clinically validated Essential Tremor Rating Assessment Scale after six months of DBS. Secondary outcomes are: disease related daily functioning, adverse effects, operation time, quality of life, patient satisfaction with treatment outcome and patient evaluation of treatment burden. Study design: The study will be a multicentre prospective randomized open label blinded (PROBE) endpoint trial comparing thalamic DBS under general versus local anesthesia. Study population: A total of 110 patients with disabling essential tremor despite optimal pharmacological treatment will be randomized. Intervention (if applicable): Patients will be randomized for asleep DBS or awake DBS. According to the standard DBS procedure, two brain-electrodes are connected to an implanted neurostimulator, which is placed subcutaneously in the subclavicular area Main study parameter/endpoints: The primary outcome measure is the change in tremor score on the Essential Tremor Rating Assessment Scale after 6 months of thalamic DBS. The secondary outcome measures are the Amsterdam Linear Disability Score for functional health status, Quality of Life in Essential Tremor Questionnaire, patient satisfaction with the treatment, patient evaluation of treatment burden, operating time, hospitalization time, change of tremor medication, side effects and complications. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: Awake DBS at present is very burdensome and by many patients and health care providers considered to be an overly invasive treatment for essential tremor. Through this trial, we aim to investigate whether asleep DBS in essential tremor can become the new treatment standard. This is expected to increase the accessibility for DBS and subsequently would allow more people with essential tremor to be helped, as well as in an earlier stage of their disease than currently; more patients will benefit for a longer time period from DBS. Asleep DBS will have a shorter procedure length. The proposed research project involves treatment options that are standard care in daily practice. The therapies will not be combined with other research products. Both treatments have a low risk of serious complications and a higher risk of minor side effects. Regular follow up will be used. Participation in this study constitutes moderate risk according to NFU criteria for human research.

Conditions

Essential Tremor; Deep Brain Stimulation; Diffusion Tensor Imaging; Magnetic Resonance; Central Nervous System Diseases

Outcome Measures

Primary Outcomes (1)

• Essential Tremor Rating Assessment Scale (TETRAS)

  The amount of decrease in motor symptoms indicated by change in the disease-specific Essential Tremor Rating Assessment Scale (TETRAS) after six months of deep brain stimulation. The TETRAS scores are between 0 and 64; higher scores indicating worse (more severe) tremor symptoms.

  assessment will be done before DBS and after 6 months of DBS

Secondary Outcomes (4)

• The Amsterdam Linear Disability Score for functional health status

  assessment will be done before DBS and after 6 months of DBS

• Quality of Life in Essential Tremor Questionnaire

  assessment will be done before DBS and after 6 months of DBS

• Global Impression of Change

  assessment will be done before DBS and after 6 months of DBS

• EQ-5D-5L

  assessment will be done before DBS and after 6 months of DBS

Study Arms (2)

55 patients with essential tremor receive awake DBS

ACTIVE COMPARATOR

Procedure: Awake DBS

55 patients with essential tremor receive asleep DBS

EXPERIMENTAL

Procedure: Asleep DBS

Interventions

Awake DBS PROCEDURE

55 patients receive awake DBS (current standard procedure)

55 patients with essential tremor receive awake DBS

Asleep DBS PROCEDURE

55 patients receive asleep DBS

55 patients with essential tremor receive asleep DBS

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age \> 18 years;
• Idiopathic essential tremor
• Disabling tremor despite optimal pharmacological treatment
• A life expectancy of at least two years

You may not qualify if:

• Legally incompetent adults;
• Previous tremor-neurosurgery (e.g., DBS, thalamotomy);
• Contraindications for DBS surgery, such as a physical disorder making surgery hazardous;
• Psychosis;
• Current depression;
• Unable to provide written informed consent.

Sponsors & Collaborators

• Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA): lead
• University Medical Center Groningen: collaborator
• Medical Center Haaglanden: collaborator
• The Elisabeth-TweeSteden Hospital: collaborator
• Maastricht University Medical Center: collaborator
• Radboud University Medical Center: collaborator
• Medisch Spectrum Twente: collaborator

Study Sites (1)

Amsterdam UMC, location AMC

Amsterdam, North Holland, 11015AZ, Netherlands

RECRUITING

Related Publications (1)

• 1. Song P, Zhang Y, Zha M, et al. The global prevalence of essential tremor, with emphasis on age and sex: A meta-analysis. J Glob Health. Apr 10 2021;11:04028. 2. Schuurman PR, Bosch DA, Merkus MP, Speelman JD. Long-term follow-up of thalamic stimulation versus thalamotomy for tremor suppression. Movement disorders : official journal of the Movement Disorder Society. Jun 15 2008;23(8):1146-1153. 3. Bot M, van Rootselaar F, Contarino MF, et al. Deep Brain Stimulation for Essential Tremor: Aligning Thalamic and Posterior Subthalamic Targets in 1 Surgical Trajectory. Oper Neurosurg (Hagerstown). Aug 1 2018;15(2):144-152. 4. Bot M, van Rootselaari AF, Odekerken V, et al. Evaluating and Optimizing Dentato-Rubro-Thalamic-Tract Deterministic Tractography in Deep Brain Stimulation for Essential Tremor. Oper Neurosurg (Hagerstown). Sep 25 2021. 5. Bot M, Pauwels R, van den Munckhof P, et al. The Fast Gray Matter Acquisition T1 Inversion Recovery Sequence in Deep Brain Stimulation: Introducing the Rubral Wing for Dentato-Rubro-Thalamic Tract Depiction and Tremor Control. Neuromodulation. Jan 15 2022. 6. Holewijn RA, Verbaan D, van den Munckhof PM, et al. General Anesthesia vs Local Anesthesia in Microelectrode Recording-Guided Deep-Brain Stimulation for Parkinson Disease: The GALAXY Randomized Clinical Trial. JAMA Neurol. Sep 7 2021. 7. Graat I, Mocking RJT, Liebrand LC, et al. Tractography-based versus anatomical landmark-based targeting in vALIC deep brain stimulation for refractory obsessive-compulsive disorder. Mol Psychiatry. Dec 2022;27(12):5206-5212. 8. Nowacki A, Barlatey S, Al-Fatly B, et al. Probabilistic Mapping Reveals Optimal Stimulation Site in Essential Tremor. Ann Neurol. May 2022;91(5):602-612. 9. Coenen VA, Sajonz B, Prokop T, et al. The dentato-rubro-thalamic tract as the potential common deep brain stimulation target for tremor of various origin: an observational case series. Acta neurochirurgica. May 2020;162(5):1053-1066. 10. Akram H, Dayal V, Mahlknecht P, et al. Connectivity derived thalamic segmentation in deep brain stimulation for tremor. Neuroimage Clin. 2018;18:130-142. 11. Nowacki A, Schlaier J, Debove I, Pollo C. Validation of diffusion tensor imaging tractography to visualize the dentatorubrothalamic tract for surgical planning. Journal of neurosurgery. Mar 23 2018;130(1):99-108. 12. Coenen VA, Allert N, Paus S, Kronenburger M, Urbach H, Madler B. Modulation of the Cerebello-Thalamo-Cortical Network in Thalamic Deep Brain Stimulation for Tremor: A Diffusion Tensor Imaging Study. Neurosurgery. Dec 2014;75(6):657-669. 13. Kremer NI, Pauwels RWJ, Pozzi NG, et al. Deep Brain Stimulation for Tremor: Update on Long-Term Outcomes, Target Considerations and Future Directions. J Clin Med. Aug 5 2021;10(16).

  BACKGROUND

MeSH Terms

Conditions

Essential Tremor; Central Nervous System Diseases

Condition Hierarchy (Ancestors)

Movement Disorders; Nervous System Diseases

Central Study Contacts

Maarten Bot, MD, PhD

CONTACT

0031621514048; m.bot@amsterdamumc.nl

Richard Schuurman, Md, PhD, professor

CONTACT

0031626908484; p.r.schuurman@amsterdamumc.nl

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Because both patient and neurosurgeon are aware of receiving general or local anesthesia, it is not possible to blind them for treatment assignment. Patients will be instructed not to reveal the received treatment with the physician performing the 6-month assessments and neuropsychological evaluation in order to secure a blinded end-point.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The study will be a multicentre prospective randomized open label blinded (PROBE) endpoint trial comparing thalamic DBS under general versus local anesthesia

Study Record Dates

• First Submitted: June 9, 2023
• First Posted: August 1, 2023
• Study Start: February 1, 2024
• Primary Completion (Estimated): July 1, 2027
• Study Completion (Estimated): July 1, 2028
• Last Updated: April 13, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: starting 2024

Locations

NL (1)