Mechanism and Application of Deep Brain Stimulation in the Treatment of Parkinson's Disease

Beijing Tiantan Hospital1 个研究点分布在 1 个国家目标入组 60 人开始时间: 2024年7月1日最近更新: 2025年5月31日

适应症

试验速览

阶段: 不适用
状态: 招募中
发起方
入组人数: 60
试验地点: 1
主要终点: Multimode neuroelectrophysiological signal recording

研究概览研究设计入排标准结局指标研究者研究点记录与标识符相似试验

研究概览

简要总结

Project name: The mechanism and application of deep brain stimulation in the treatment of Parkinson's disease

Objective:

To test the hypothesis that electrical stimulation of substantia nigra regulates cognitive dysfunction in Parkinson's disease and to reveal its electrophysiological mechanism.

Study design:

This study is a self-controlled prospective cohort study. By comparing the behavioral characteristics of the memory paradigm under microelectrode stimulation during DBS operation and the characteristics of the underlying electrophysiological signals, and the behavioral characteristics of the memory paradigm and the characteristics of brain network activity under electrical stimulation when DBS is turned on 1 month after surgery. The regulatory effect of substantia nigra DBS on memory network was analyzed.

Cases: 60

Case selection:

Inclusion criteria:

1)Voluntarily participate in the clinical study and sign the informed consent; 2) Age 50-70 years old, gender unlimited; 3) The clinical diagnosis is consistent with typical PD, and the medical history is less than 20 years; 4) Patients who intend to use 3.0T magnetic resonance compatible dual-channel DBS device (G106R or G106RS, Beijing Pinchi Company) for bilateral subthalamic nucleus DBS surgery to control PD symptoms; 5) MRI excluded patients with obvious structural changes; 6) The visual acuity and hearing of the subjects were basically normal, and the compliance was good, and they could complete the tasks listed in the experimental scheme in accordance with the standards.

Exclusion criteria:

1)Serious mental, cognitive and psychological disorders, unable to sign informed consent or cooperate with the operation and various tasks; 2) There are contraindications for neurosurgery, such as hydrocephalus, cerebral atrophy, cerebrovascular sequelae, heart disease and other cardiovascular and cerebrovascular diseases; 3) There are concomitant diseases that seriously affect health, such as tumors, serious abnormalities of liver and kidney function (indexes more than 3 times normal); 4) There is intracranial space occupation, cerebrovascular disease, mental illness, other neurological diseases, claustrophobia, or there is an implant in the body, which affects the nuclear magnetic scan; 5) The results of the Mini-Mental State Scale (MMSE) <24 or the Montreal Cognitive Assessment Scale (MoCA) <18 in the preoperative assessment, or the results of other scales indicate the presence of severe dementia.

therapeutic schedule： This study did not change the patient's overall treatment regimen, and only electrical stimulation was tested during and after DBS surgery

Efficacy evaluation:

Effectiveness evaluation index (primary efficacy index and secondary efficacy index) : accuracy of memory paradigm, response speed Safety evaluation indicators: blood pressure, heart rate, dual frequency index, patient complaints and symptoms

Statistical methods:

The group t test was used to compare the normal distribution between the measurement data groups. For measurement data with non-normal distribution, Wilcoxon rank sum test was used for comparison between groups.

The study period is January 1, 2024 - December 31, 2026.

详细描述

Research background The core symptoms of Parkinson's disease (PD) include motor symptoms and non-motor symptoms, among which cognitive dysfunction is the most common and one of the most overlooked non-motor symptoms in patients with advanced PD. Cross-sectional studies have shown that up to 40% of PD patients are combined with cognitive dysfunction at the time of diagnosis, which is manifested by functional decline in memory, executive, attention, language, visuospatial ability and other cognitive subfields. Among them, the memory impairment subtype with episodic memory function decline as the main manifestation is the most common and the fastest progressing. About 10% to 15% of patients with these manifestations will progress to dementia each year, which is four to six times higher than the age-matched non-PD population, and more than 80% of patients with PD will develop dementia within 10 years of diagnosis of PD. This increasing cognitive and memory dysfunction seriously affects the quality of life of patients and the overall treatment effect, often leading to accelerated deterioration of the disease, bringing a heavy burden to the family and society. It can be seen that in-depth exploration of the formation mechanism of PD cognitive and memory dysfunction and the establishment of effective intervention means have become an important proposition to be solved urgently in the field of PD research.

The research group previously tested the behavioral changes of rats in the low frequency electric stimulation group of substantia nigra and the sham stimulation group using behavioral experiments such as nesting experiment and water maze experiment, and found that rats in the low frequency electric stimulation group performed better in the nesting experiment and water maze experiment, suggesting that low frequency electric stimulation of substantia nigra can improve the memory behavioral performance of rats with Parkinson's disease.

The applicant's previous study found that deep brain stimulation (DBS) is an effective means to treat Parkinson's disease, and low frequency electrical stimulation of the substantia nigra can improve episodic memory function in patients with Parkinson's disease. Therefore, the applicant team intends to further study the regulatory effect and mechanism of substantia nigra electrical stimulation on episodic memory, reveal the mechanism of its improvement of cognitive function from the theoretical level, clarify its regulatory effect on cognitive impairment from the technical level, and verify the potential of its treatment of cognitive impairment from the application level, so as to solve the major clinical needs in the diagnosis and treatment of PD cognitive impairment. Bring the Gospel to 5 million PD patients, and help the construction of Beijing International Science and Technology Innovation Center.

Research purpose

Main Objective: To verify the hypothesis that electrical stimulation of substantia nigra can regulate cognitive dysfunction in Parkinson's disease, and to reveal its electrophysiological mechanism.
Secondary objective: To explore the safety and side effects of electrical stimulation of substantia nigra in regulating cognitive dysfunction.

研究设计

研究类型: Interventional
分配方式: Na
干预模型: Single Group
主要目的: Treatment
盲法: None

入排标准

年龄范围: 50 Years 至 70 Years（Adult, Older Adult）
性别: All
接受健康志愿者: 否

入选标准

•Voluntarily participate in the clinical study and sign the informed consent;
•Age 50-70 years old, gender unlimited;
•The clinical diagnosis is consistent with typical PD, and the medical history is less than 20 years;
•Patients who intend to use 3.0T magnetic resonance compatible dual-channel DBS device (G106R or G106RS, Beijing Pinchi Company) for bilateral subthalamic nucleus DBS surgery to control PD symptoms;
•MRI excluded patients with obvious structural changes;
•The visual acuity and hearing of the subjects were basically normal, and the compliance was good, and they could complete the tasks listed in the experimental scheme in accordance with the standards.

排除标准

•Serious mental, cognitive and psychological disorders, unable to sign informed consent or cooperate with the operation and various tasks;
•There are contraindications for neurosurgery, such as hydrocephalus, cerebral atrophy, cerebrovascular sequelae, heart disease and other cardiovascular and cerebrovascular diseases;
•There are concomitant diseases that seriously affect health, such as tumors, serious abnormalities of liver and kidney function (indexes more than 3 times normal);
•There is intracranial space occupation, cerebrovascular disease, mental illness, other neurological diseases, claustrophobia, or there is an implant in the body, which affects the nuclear magnetic scan;
•The results of the Mini-Mental State Scale (MMSE) <24 or the Montreal Cognitive Assessment Scale (MoCA) <18 in the preoperative assessment, or the results of other scales indicate the presence of severe dementia.

结局指标

主要结局

Multimode neuroelectrophysiological signal recording

时间窗: During DBS surgery

In this study, the spike potential and local field potential signals at the location of the microelectrode tip were recorded simultaneously, and the cortical potential signals of the dorsolateral prefrontal cortex were collected by a custom-made ring electrode to analyze the spatio-temporal characteristics of the SN and the dorsolateral prefrontal cortex during the formation of episodic memory encoding. The microelectrode recorded microvolt electrophysiological signals within 0.2-0.3mm around the microelectrode. The macroelectrode recorded the surrounding local field potential signal. In this way, the spike potential signal and local field potential signal at the tip of the microelectrode, the local field potential signal 3mm behind the tip, and the cortical potential signal could be recorded synchronously.

Frontal Lobe Function Rating Scale