Optimizing Adaptive Deep Brain Stimulation for Parkinson's Disease
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 35
- 试验地点
- 1
- 主要终点
- Prevalence and Spectral Properties of STN Local Field Potential Peaks
研究概览
简要总结
Parkinson's disease (PD) affects more than 10 million people worldwide and causes progressive motor symptoms such as slowness, stiffness and tremor. For patients whose symptoms are no longer adequately controlled with medication, deep brain stimulation (DBS) can substantially improve motor function. More recently, adaptive DBS (aDBS) has become available. Unlike conventional DBS, which delivers continuous stimulation, aDBS automatically adjusts stimulation in response to brain activity recorded by the implanted device.
Current clinical aDBS programming is based primarily on brief recordings obtained during clinic visits. However, Parkinson's symptoms and the underlying brain signals change throughout the day in response to medication, daily activities and other factors. As a result, recordings collected during a single clinic visit may not fully capture the neural activity that best reflects a patient's symptoms in everyday life.
The purpose of this study is to determine whether incorporating long-term brain recordings collected during daily life improves adaptive DBS programming and clinical outcomes. Participants will first undergo in-clinic testing to identify brain signals associated with their symptoms. Brain activity and symptoms will then be monitored during everyday life using the sensing capabilities of the implanted DBS device. Participants with suitable brain signals will enter a randomized, blinded crossover study comparing three stimulation approaches: conventional continuous DBS, adaptive DBS programmed using the current clinic-based approach and adaptive DBS programmed using both clinic and at-home recordings.
The study will compare the effects of these approaches on motor fluctuations and quality of life. It will also determine how frequently different brain signals occur in people with Parkinson's disease and how well they reflect motor symptoms, providing information that may improve future adaptive DBS therapies.
详细描述
Adaptive deep brain stimulation (aDBS) automatically adjusts stimulation based on brain activity recorded by an implanted deep brain stimulation (DBS) system. Current clinical programming of aDBS relies on recordings of brain activity collected during brief clinic visits. However, Parkinson's disease symptoms and the underlying brain activity fluctuate throughout the day in response to medication, daily activities and other factors. It is unknown whether recordings collected during routine clinic visits adequately capture the brain signals needed to optimize adaptive DBS for everyday life.
Commercially available sensing-enabled DBS systems now allow chronic recording of brain activity during everyday life. These recordings provide an opportunity to characterize patient-specific brain signals under real-world conditions and determine whether incorporating this information improves adaptive DBS programming and clinical outcomes.
This study addresses two primary questions:
- Does more comprehensive in-clinic characterization of brain signals across medication states improve adaptive DBS programming compared with the current clinic-based approach?
- Does incorporating chronic at-home recordings of brain activity further improve adaptive DBS programming and clinical outcomes?
The study consists of two sequential parts.
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, Investigator, Outcomes Assessor)
盲法说明
Participants and outcome raters are blinded to the stimulation condition. The unblinded programmer is responsible for setting up device groups. cDBS control uses a "sham adaptive" active control setting - all parameters will be configured to appear as if an adaptive algorithm is active, but stimulation amplitude will remain fixed at the standard cDBS level. This ensures the program appears as an adaptive option on the patient programmer while maintaining blinding.
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
- •Subjects will be 18 and over
- •Clinical diagnosis of idiopathic Parkinson's disease (PD), consistent with MDS diagnostic criteria
- •Motor fluctuations in response to medication
- •Bilateral subthalamic nucleus (STN) DBS using a commercial sensing-enabled device
- •Stable cDBS settings for ≥3 months prior to enrollment
- •Stable antiparkinsonian medication regimen for ≥4 weeks prior to enrollment
- •Capacity to provide informed consent
- •Ability and willingness to complete study visits and at-home monitoring
- •For Part 2: Presence of an adequate STN neural signal (e.g., stable LFP feature suitable for biomarker extraction) during screening
- •Ability to speak and understand English sufficiently to provide informed consent and complete study procedures and assessments without an interpreter.
排除标准
- •Atypical or secondary parkinsonism (e.g., multiple system atrophy, progressive supranuclear palsy, vascular parkinsonism)
- •Prior brain surgery other than STN DBS
- •Clinically significant cognitive impairment or dementia, defined as MoCA < 24 or equivalent, or lacking capacity to provide informed consent
- •Active psychiatric illness that could compromise safety or participation (e.g., uncontrolled depression, psychosis, severe anxiety disorder)
- •History of suicidality or suicide attempt within the past year
- •Clinically unstable medical conditions (e.g., uncontrolled hypertension, advanced cardiac or pulmonary disease) that would increase study risk
- •Current substance abuse or dependence
- •Ongoing participation in another interventional trial that could confound outcomes
- •Pregnancy or plans to become pregnant during the study period
- •Inability or unwillingness to comply with study procedures (e.g., at-home monitoring, study visits, data collection)
研究组 & 干预措施
aDBS-Extended
Adaptive DBS 1 - Extended (aDBS-Extended): neural signal biomarkers and thresholds established through an extended optimization protocol that integrates in-clinic and at-home recordings across multiple medication states. Participants receive this condition for 1 week per block, repeated 8 times over ~6 months in randomized crossover with the other two conditions.
干预措施: aDBS-Extended (Medtronic Percept™) (Device)
aDBS-Standard
Adaptive DBS 2 - Standard (aDBS-Standard): neural signal biomarkers and thresholds optimized during short, limited programming sessions, consistent with Medtronic's recommended clinical procedure. Participants receive this condition for 1 week per block, repeated 8 times over ~6 months in randomized crossover with the other two conditions.
干预措施: aDBS-Standard (Medtronic Percept™) (Device)
Continuous DBS (cDBS) - Active Control
Continuous DBS (cDBS, active control): constant amplitude at the participant's stable clinical setting. Biomarker and frequency band parameters will be recorded but will not modulate stimulation. Participants receive this condition for 1 week per block, repeated 8 times over ~6 months in randomized crossover with the other two conditions.
干预措施: Continuous DBS (cDBS) - Active Control (Medtronic Percept™) (Device)
结局指标
主要结局
Prevalence and Spectral Properties of STN Local Field Potential Peaks
时间窗: Neural recordings obtained during 1 in-clinic session. For participants in Part 2, selected neural biomarker will be recorded for 14 days, and symptom and medication logs completed on 3 of those days. Events are recorded for predefined symptoms.
Prevalence and spectral properties of STN local field potential (LFP) peaks (beta: 13-30 Hz; gamma: 60-90 Hz), and their modulation by dopaminergic medication state.
Percent Time With Most Bothersome Motor Symptom
时间窗: Daily assessment over each 1-week treatment block; repeated 8 times per condition over approximately 6 months.
Percent time of the most bothersome motor symptom, assessed via electronic self-ratings (Oehrn et al., Nature Medicine, 2024). Primary outcome measures will be derived from nightly self-reports, including time spent with the most bothersome motor symptom (hours/day) and time awake (hours/day). The outcome is calculated as the percentage of waking hours spent with the most bothersome motor symptom (hours with symptom ÷ waking hours × 100).
Severity of Most Bothersome Motor Symptom
时间窗: Daily assessment over each 1-week treatment block; repeated 8 times per condition over approximately 6 months
Self-reported severity of the most bothersome motor symptom. Symptom severity (0-10 scale). Scores range from 0 (no symptoms) to 10 (worst possible symptoms); higher scores indicate worse outcome.
Quality of Life (EQ-5D-5L)
时间窗: Daily assessment over each 1-week treatment block; repeated 8 times per condition over approximately 6 months
Quality of life will be assessed using the EuroQol 5-Dimension 5-Level questionnaire (EQ-5D-5L), including the EQ Visual Analogue Scale (EQ VAS; range 0-100), with higher scores indicating better perceived health.
次要结局
- Medication-Related Modulation of STN Local Field Potential Spectral Power(During the in-clinic testing session)
- Wearable-Derived Motor Symptoms Across DBS Conditions(Continuous wearable monitoring during each 1-week treatment block, repeated 8 times per condition over approximately 6 months.)
- Regression of Wearable-Derived Motor Measures on Patient-Specific STN Neural Biomarker Activity(At-home neural and wearable recordings over 14 days.)
研究者
Carina Renate Oehrn
Assistant Professor of Neurological Surgery
University of California, Davis