Mechanism and Application of DBS in the Treatment of PD
ConditionParkinson's Disease and Parkinsonism
Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexAll
Age50-70
SponsorBeijing Tiantan Hospital
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
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;
Disqualifiers
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;
Trial design
Design model
Single group
Treatments tested in this trial
microelectrode stimulation of DBS
DeviceContact selection: According to the electrode position in the image (target reconstruction through CT scan), the electrode located in the substantia nigra is selected as the negative electrode, the contact near the upper part of the substantia nigra is selected as the positive electrode, and the bipolar stimulation mode is selected. Stimulation parameters: The frequency was selected as 0/10/130Hz, the pulse width remained unchanged at 90μs, the side effects of patients were observed, and the voltage was slowly increased to 2.0V; The patient voltage was 0 during the spurious stimulation. The washout period was 1 hour
Treatment groups
60 Participants
are divided into 1 treatment groupGroup A: Intraoperative and One month after the operation microelectrode stimulation of DBSExperimental treatment 1 intervention
Trial outcomes
Primary outcomes
1
Changes in recognition accuracy of new/old objects between baseline and under electrical stimulation
In this project, after the microelectrode was inserted into the substantia nigra during DBS surgery, the memory paradigm test was started, and some memory stimuli were presented with electrical stimulation test at the same time, so as to observe the baseline memory accuracy of the subjects and the changes in the recognition accuracy of new/old objects under the state of electrical stimulation. The memory paradigm test was performed in the ward after surgery to evaluate the cognitive function of the subjects
Time frame
From the middle of DBS surgery to one month after surgery2
Changes of fMRI signal and connectivity in brain functional areas
In this study, SPM12 and DPABI were used to preprocess the resting-state fMRI data and calculate the functional connectivity, locate the location of the dorsolateral prefrontal lobe, establish the resting-state brain network between the substantia nigra and the dorsolateral prefrontal lobe, calculate the functional connectivity between the substantia nigra and the dorsolateral prefrontal lobe, and design the surgical path. The maximum functional connectivity between the dorsolateral prefrontal cortex, substantia nigra and subthalamic nucleus was calculated according to the results of resting-state fMRI. All subjects underwent 7.0T and 3.0T MR Scans before and after surgery, respectively. Scanning sequences included 3D-T1-weighted images, axial coronal T2-weighted images, 3D-Flair sequences, etc. In addition, all participants completed the resting-state and task-state fMRI scans before and after the operation, and the post-operation task-state fMRI scan was performed with DBS on
Time frame
From preoperative to one month postoperative3
Multimode neuroelectrophysiological signal recording
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.
Time frame
During DBS surgery4
Mini-mental State Examination Score
The DBS device was implanted at the subthalamic nucleus. According to the electrophysiological signal during the operation, the lowest contact of the DBS electrode was implanted into the substantia nigra, and the remaining contacts were implanted into the subthalamic nucleus. The cognitive memory function of the patients was assessed by Mini-mental State Examination before surgery, and then the cognitive memory function of the patients in no stimulation, low frequency and high frequency substantia nigra DBS states was assessed by Mini-mental State Examination Score one month after surgery. The effects of substantia nigra DBS with different parameters on the memory function of PD subjects were analyzed. The scale has a minimum value of 0 and a maximum value of 30, with higher scores indicating better outcomes.
Time frame
From preoperative to one month postoperativeSponsors and contacts
Click on the lead sponsor to view all of their trials.
Beijing Tiantan Hospital
Lead sponsor
Institute of Biotechnology, Academy of Military Medical Sciences, PLA of China
Collaborator
Tsinghua University
Collaborator
Boston Children's Hospital
Collaborator
Source ClinicalTrials.gov