Multi-targets, Single-lead GPi+NBM DBS in Parkinson's Disease With Mild Cognitive Impairment
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 6
- 试验地点
- 2
- 主要终点
- Change in motor function (UPDRS)GPi/NBM DBS
研究概览
简要总结
This study examines the safety and feasibility of DBS in treating the movement and cognitive dysfunction in Parkinson's disease (PD). Globus pallidus interna (GPi) stimulation is an established treatment for the motor symptoms in PD, but it does not treat the cognitive symptoms that can also be seen in this condition. It is theorized that we can improve cognitive dysfunction by stimulating a part of the brain called the nucleus basalis of Meynert (NBM), which releases a chemical (acetylcholine) and plays a role in memory and attention. By using a novel DBS system (Vercise device) with 2 electrodes that are designed to stimulate the GPi and NBM, we can potentially target the motor and cognitive symptoms of PD with a single intervention.
详细描述
Neuronal loss within the cholinergic nucleus basalis of Meynert (NBM) correlates with cognitive decline in dementing disorders such as Alzheimer's disease and Parkinson's disease (PD). Deep Brain Stimulation targeting the Globus Pallidus interna (GPi) is an established treatment for the motor symptoms in Parkinson's Disease, and stimulating the NBM is believed to stimulate cognitive function. Targeting these two regions was previously impossible because they require different frequency stimulations, but recent developments in DBS technology allow for the dual stimulation of these nuclei at different frequencies.
This phase-II double-blind cross-over pilot trial will investigate the motor and cognitive effects as well as the presence of adverse effects of combined NBM and GPi DBS. The main goal of this pilot trial is to demonstrate the feasibility and safety of the multi-targeting approach in 6 patients with PDD and disabling motor symptoms.
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
- Double (Participant, Outcomes Assessor)
盲法说明
- The post-surgical double-blind cross-over phase with randomization will follow once programming settings are determined. Under constant GPi DBS, patients will receive NBM DBS active or sham for 8 weeks followed by an 8-week cross-over. Then, patients will enter a post-surgical open-label follow-up phase during which they will receive GPi+NBM DBS.
- The outcomes assessor is blinded to the whether the NBM DBS is active to avoid bias while analyzing the data
入排标准
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •PD-MCI that affects multiple cognitive domains (including memory, visuo-spatial deficits etc.). diagnosis based on a comprehensive neuropsychological assessment (gold-standard) allowing the application of Level II MDS diagnostic criteria (Dubois et al. 2007)
- •PD fulfilling standard criteria for bilateral GPi DBS surgery
- •Patient's ability to provide informed consent and comply with study protocol.
排除标准
- •Severe Parkinson's disease dementia, preventing completion of the neuropsychological assessment, compliance with the study protocol, or ability to provide informed consent.
- •Inability to be fluent in English.
- •Unstable dose of any cognitive enhancing medication.
- •Presence of other neurological disorders, severe active psychiatric conditions or previous brain surgery.
- •Other conditions contraindicating DBS, PET scanning or MRI scanning.
结局指标
主要结局
Change in motor function (UPDRS)GPi/NBM DBS
时间窗: at baseline and 6, 14, 22, 30 and 52 weeks post surgery
Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) is a comprehensive 65 item assessment of both motor and non-motor symptoms associated with Parkinson's Disease. Each symptom is rated on a 5-point scale (from 0 to 4), and the maximum total score is 199, indicating severe impairment from parkinson's disease.
Change in cognition after GPi/NBM DBS
时间窗: at baseline and 6, 14, 22, 30 and 52 weeks post surgery
This will be measured by the ADAS-Cog 13, verbal fluency test and sustained attention task.
To assess the occurrence of adverse events from GPi/NBM DBS and occurrence of adverse events.
时间窗: through study completion, an average of 1 year
We define an adverse event (AE) as any untoward medical occurrence that occurs in the course of this study whether or not considered related to the study device, study procedures or study requirements that is identified or worsens during the study.
次要结局
- To assess the impact on health-related quality-of-life and various non-motor symptoms of PD(1 year)
- To use neuroimaging biomarkers (MEG and FDG-PET) to examine localized effects of NBM stimulation(with NBM turned on and off, 22 and 30 weeks after surgery respectively)
研究者
Alfonso Fasano
Dr. Alfonso Fasano, MD, PhD, Professor, Department of Medicine, Division of Neurology at University of Toronto, Toronto Western Hospital
University of Toronto