Multicentre RCT of Awake Versus Asleep Tractography Based DBS for ET (TREMBLE)
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|ClinicalTrials.gov Identifier: NCT05968976|
Recruitment Status : Recruiting
First Posted : August 1, 2023
Last Update Posted : August 1, 2023
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.
|Condition or disease||Intervention/treatment||Phase|
|Essential Tremor Deep Brain Stimulation Diffusion Tensor Imaging Magnetic Resonance Central Nervous System Diseases||Procedure: Awake DBS Procedure: Asleep DBS||Not Applicable|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||110 participants|
|Intervention Model:||Parallel Assignment|
|Intervention Model Description:||The study will be a multicentre prospective randomized open label blinded (PROBE) endpoint trial comparing thalamic DBS under general versus local anesthesia|
|Masking:||Single (Outcomes Assessor)|
|Masking Description:||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.|
|Official Title:||The TREMBLE Study: Multicentre Randomized Controlled Trial of Awake Versus Asleep Tractography Based Deep Brain Stimulation for Essential Tremor|
|Estimated Study Start Date :||September 1, 2023|
|Estimated Primary Completion Date :||July 1, 2027|
|Estimated Study Completion Date :||July 1, 2028|
|Active Comparator: 55 patients with essential tremor receive awake DBS||
Procedure: Awake DBS
55 patients receive awake DBS (current standard procedure)
|Experimental: 55 patients with essential tremor receive asleep DBS||
Procedure: Asleep DBS
55 patients receive asleep DBS
- Essential Tremor Rating Assessment Scale (TETRAS) [ Time Frame: assessment will be done before DBS and after 6 months of DBS ]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.
- The Amsterdam Linear Disability Score for functional health status [ Time Frame: assessment will be done before DBS and after 6 months of DBS ]The Amsterdam Linear Disability Score (ALDS) is a generic itembank which measures disability, as expressed by the ability to perform activities of daily living. These scores are linearly transformed into values between 0 and 100. Lower scores indicate more disability.
- Quality of Life in Essential Tremor Questionnaire [ Time Frame: assessment will be done before DBS and after 6 months of DBS ]The Quality of Life in Essential Tremor Questionnaire (QUEST) is a 30-item scale developed specifically for patients with essential tremor to measure items impacting perceived quality of life (QOL) that generic QOL measures do not effectively capture, including activities of daily living that are affected by essential tremor. The QUEST was made to be relatively brief and easy for patients to use.
- Global Impression of Change [ Time Frame: assessment will be done before DBS and after 6 months of DBS ]The CGI provides an overall clinician-determined summary measure that takes into account all available information, including a knowledge of the patient's history, psychosocial circumstances, symptoms, behavior, and the impact of the symptoms on the patient's ability to function. The CGI actually comprises two companion one-item measures evaluating the following: (a) severity of psychopathology from 1 to 7 and (b) change from the initiation of treatment on a similar seven-point scale.
- EQ-5D-5L [ Time Frame: assessment will be done before DBS and after 6 months of DBS ]
The EQ-5D-5L consists of 2 pages: the EQ-5D descriptive system and the EQ visual analogue scale (EQ VAS). The descriptive system comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The digits for the five dimensions can be combined into a 5-digit number that describes the patient's health state.
The EQ VAS records the patient's self-rated health on a vertical visual analogue scale, where the endpoints are labelled 'The best health you can imagine' and 'The worst health you can imagine'. The VAS can be used as a quantitative measure of health outcome that reflect the patient's own judgement.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05968976
|Contact: Maarten Bot, MD, PhDfirstname.lastname@example.org|
|Contact: Richard Schuurman, Md, PhD, email@example.com|