The TREMBLE Study: Multicentre Randomized Controlled Trial of Awake Versus Asleep Tractography Based Deep Brain Stimulation for Essential Tremor
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 110
- 试验地点
- 2
- 主要终点
- Essential Tremor Rating Assessment Scale (TETRAS)
研究概览
简要总结
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.
详细描述
INTRODUCTION AND RATIONALE
Essential tremor Essential tremor is the most common neurological movement disorder and often begins at an early age. In 20 to 30 years, the disorder develops to an advanced stage, in which patients are severely disabled by the tremor (trembling, shaking) of their hands in particular (and additional shaking of the head, legs and vocal cords may occur). In most severe cases, drug treatment only partially suppresses the tremor, and also loses effect over time. As a result, patients can no longer use their hands properly, for example, when eating and carrying out their activities of daily living. Patients become care-dependent. In addition, the involuntary tremor is socially disruptive and prevents patients from showing up in public places; they become socially isolated.
Because the tremor increases gradually in severity (over decades), patients and their immediate environment adapt their lives accordingly. For example, they drink with a straw, eat foods that are easy to scoop up and avoid social occasions because the trembling is perceived as disturbing. Often the possibility of treatment with DBS could have been considered years earlier, however this possibility is unknown to both patient and caregiver, or the DBS is seen as experimental.
Thalamic DBS is an effective surgical treatment for patients with disabling essential tremor who have severe limitations in their functioning despite pharmacological treatment. During the surgical placement of DBS brain electrodes, patients are awake so that the effect of the electrode implantation can be monitored. Awake DBS surgery is extremely burdensome and therefore prevents many patients from undergoing the treatment. To increase accessibility to DBS, we want to perform the surgery asleep.
Functional stereotactic neurosurgery Currently the standard DBS procedure is performed awake. Patients need to be awake during the surgery as the optimal placement of the stimulation electrodes into the brain is confirmed by intra-operative clinical testing. This procedure is extremely burdensome for patients: 1) cranial injections are needed for local anesthesia 2) a frame is fixed to their head with four bone-pins 3) they are secured to the operating table for the procedure 4) burr holes are drilled into their skull and 5) electrodes are implanted during which patients are hours continuously tested for DBS effect.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
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.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age > 18 years;
- •Idiopathic essential tremor
- •Disabling tremor despite optimal pharmacological treatment
- •A life expectancy of at least two years
排除标准
- •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.
结局指标
主要结局
Essential Tremor Rating Assessment Scale (TETRAS)
时间窗: 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.
次要结局
- 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)
- The Amsterdam Linear Disability Score for functional health status(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)
研究者
Maarten Bot
Principal Investigator
Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)