Circadian Adaptive Deep Brain Stimulation in Essential Tremor
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 25
- 试验地点
- 2
- 主要终点
- Presence of thalamic circadian rhythm
研究概览
简要总结
Deep brain stimulation (DBS) of the thalamus is an effective treatment for medically refractory essential tremor (ET). DBS involves delivering continuous stimulation to the brain through electrodes permanently implanted in the thalamus. Despite proven effectiveness, the long-term benefit of DBS can wane over time (habituation) and side effects, including paresthesia and dysarthria, often limit the amplitude of the stimulation, resulting in suboptimal control of tremor. In clinical practice, many groups advise patients to switch their devices off at night to avoid habituation and reduce side effects. However, manually turning off the device at night can result in uncontrolled tremor when the patient moves at night.
This study aims to develop an algorithm that automatically turns off stimulation when a patient is asleep, based on circadian brain signals. Turning off stimulation could potentially improve the therapy by limiting adverse effects, increasing efficacy, reducing the risk of habituation, and prolonging battery life. This study will evaluate the feasibility, safety, and tolerability of circadian adaptive DBS.
详细描述
This single-center study will investigate the feasibility of developing an adaptive Deep brain stimulation (aDBS) strategy using thalamic circadian rhythm as a control signal. It will evaluate the safety and tolerability of aDBS compared to conventional DBS (cDBS) in a double-blinded cross-over design.
This study will recruit 25 Essential Tremor (ET) patients implanted with the bidirectional neural interface, Medtronic Percept PC (FDA approved), attached to DBS directional lead(s) (Sensight) implanted unilaterally or bilaterally in the ventral intermediate nucleus (VIM) and who are receiving adequate control of their tremor with VIM DBS.
First, the brain signal will be recorded for 1 month to identify circadian fluctuations that may be used to identify the period of sleep. Second, for each patient, an aDBS algorithm based on individualized brain activity will be developed and tested for 2 weeks in a double-blinded cross-over design comparing aDBS and cDBS. Third, at the end of this 4-week trial, patients who preferred aDBS will have the opportunity to stay on aDBS for 6 months, allowing to assess the long-term tolerability of the aDBS.
Each patient enrolled in this study will participate in 7 study visits over 8 months during which chronic brain recordings and aDBS will be set up. Symptoms and stimulation-induced side effects will be assessed by clinicians during these visits. Self-rating scales and wearable will be provided to track tremor, sleep, and movement at home.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 21 Years 至 89 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Diagnosis of Essential Tremor confirmed by a Movement Disorders specialist following established criteria recommended by the Movement Disorders Society
- •Patients implanted with unilateral or bilateral VIM DBS leads attached to the Medtronic Percept DBS device for the treatment of Essential Tremor
- •Patients with clinical benefit of DBS as defined by a 30% improvement on the TRS or TETRAS at least 3 months after DBS implantation
- •DBS programmed in a monopolar configuration allowing chronic brain sensing (C+1- or C+2- in ring mode or any direction)
- •Be between 21 and 89 years old
- •Ability to give informed consent for the study
排除标准
- •Inability to comply with the study protocol
- •Pregnancy: all women of childbearing potential will have a negative urine pregnancy test prior to undergoing the study
- •Current active suicidal ideation (Yes to #2-5 on C-SSRS)
- •Any personality or mood symptoms that study personnel believe will interfere with study requirements
研究组 & 干预措施
Adaptive DBS, Then Conventional DBS
Participants will initially have their DBS programmed to automatically turn off during sleep for 2 weeks. Then, they will transition to continuous stimulation for another 2 weeks.
干预措施: Circadian Adaptive DBS (Device)
Adaptive DBS, Then Conventional DBS
Participants will initially have their DBS programmed to automatically turn off during sleep for 2 weeks. Then, they will transition to continuous stimulation for another 2 weeks.
干预措施: Conventional DBS (Device)
Conventional DBS, then Adaptive DBS
Participants will initially have their DBS programmed with continuous stimulation for 2 weeks. Then, they will transition to having their DBS automatically turned off during sleep for another 2 weeks.
干预措施: Circadian Adaptive DBS (Device)
Conventional DBS, then Adaptive DBS
Participants will initially have their DBS programmed with continuous stimulation for 2 weeks. Then, they will transition to having their DBS automatically turned off during sleep for another 2 weeks.
干预措施: Conventional DBS (Device)
结局指标
主要结局
Presence of thalamic circadian rhythm
时间窗: Baseline (first month of study participation)
Thalamic circadian rhythm is defined as a significant difference in day vs night brain activity. It can be used to set up adaptive DBS.
Incidence of stimulation-induced adverse events with aDBS compared to cDBS
时间窗: Double-blind crossover period (second month of study participation)
Adverse events are monitored the entire time subject is enrolled in study. Stimulation-induced adverse events during the double-blind crossover is a primary endpoint.
Presence of thalamic circadian rhythm
时间窗: Baseline (first month of study participation)
Thalamic circadian rhythm is defined as a significant difference in day vs night brain activity. It can be used to set up adaptive DBS.
Incidence of stimulation-induced adverse events with aDBS compared to cDBS
时间窗: Double-blind crossover period (second month of study participation)
Adverse events are monitored the entire time subject is enrolled in study. Stimulation-induced adverse events during the double-blind crossover is a primary endpoint.
次要结局
- Sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI), adapted for a 2-week assessment(From enrollment to the end of study (8 months))
- Patient's quality of life as assessed by the Quality of Life in Essential Tremor Questionnaire (QUEST), adapted for a 2-week assessment(From enrollment to the end of study (8 months))
- The Tremor Research Group Essential Tremor Rating Scale (TETRAS) Activities of Daily Living Subscale(From enrollment to the end of study (8 months))
- Patient's cognition as assessed by the Montreal Cognitive Assessment 5-Minute Protocol (Mini MoCA)(From enrollment to the end of study (8 months))
- Patient's mood as assessed by the Beck Depression Inventory-II (BDI-II), adapted for a 2-week assessment(From enrollment to the end of study (8 months))
- Patient's impression as assessed by the Patient Global Impression of Change Scale (PGI-C)(From enrollment to the end of study (8 months))
- Patient's self-report of side effects, tremor severity, and sleep(From enrollment to the end of study (8 months))
- Battery drainage/Stimulation energy use as assessed by Total Electrical Energy Delivered (TEED)(From enrollment to the end of study (8 months))
- Patient's quality of life as assessed by the Quality of Life in Essential Tremor Questionnaire (QUEST), adapted for a 2-week assessment(From enrollment to the end of study (8 months))
- The Tremor Research Group Essential Tremor Rating Scale (TETRAS) Activities of Daily Living Subscale(From enrollment to the end of study (8 months))
- Sleep quality as assessed by the Pittsburgh Sleep Quality Index (PSQI), adapted for a 2-week assessment(From enrollment to the end of study (8 months))
- Patient's impression as assessed by the Patient Global Impression of Change Scale (PGI-C)(From enrollment to the end of study (8 months))
- Patient's cognition as assessed by the Montreal Cognitive Assessment 5-Minute Protocol (Mini MoCA)(From enrollment to the end of study (8 months))
- Patient's mood as assessed by the Beck Depression Inventory-II (BDI-II), adapted for a 2-week assessment(From enrollment to the end of study (8 months))
- Patient's self-report of side effects, tremor severity, and sleep(From enrollment to the end of study (8 months))
- Battery drainage/Stimulation energy use as assessed by Total Electrical Energy Delivered (TEED)(From enrollment to the end of study (8 months))
- Presence/severity of tremor tracked with wearable device(From enrollment to the end of double-blind crossover period (first two months of study))