NCT06400017

Brief Summary

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
60

participants targeted

Target at P25-P50 for not_applicable

Timeline
7mo left

Started Jul 2024

Typical duration for not_applicable

Geographic Reach
1 country

1 active site

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress74%
Jul 2024Dec 2026

First Submitted

Initial submission to the registry

April 11, 2024

Completed
25 days until next milestone

First Posted

Study publicly available on registry

May 6, 2024

Completed
2 months until next milestone

Study Start

First participant enrolled

July 1, 2024

Completed
1.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2025

Completed
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2026

Expected
Last Updated

May 31, 2025

Status Verified

May 1, 2025

Enrollment Period

1.5 years

First QC Date

April 11, 2024

Last Update Submit

May 27, 2025

Conditions

Parkinson's Disease and Parkinsonism

Keywords

Cognitive dysfunctionElectrical stimulation of substantia nigra

Outcome Measures

Primary Outcomes (10)

  • 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

    From the middle of DBS surgery to one month after surgery

  • 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

    From preoperative to one month postoperative

  • 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.

    During DBS surgery

  • 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.

    From preoperative to one month postoperative

  • Montreal Cognitive Assessment 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 Montreal Cognitive Assessment 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 Montreal Cognitive Assessment 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.

    From preoperative to one month postoperative

  • Frontal Lobe Function Rating Scale

    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 Frontal Lobe Function Rating Scale 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 Frontal Lobe Function Rating Scale 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 18, with higher scores indicating better outcomes.

    From preoperative to one month postoperative

  • Trail Making Test Time

    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 Trail Making Test 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 Trail Making Test Time 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 300, with higher scores indicating worse outcomes.

    From preoperative to one month postoperative

  • Auditory Verbal Learning Test

    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 Auditory Verbal Learning Test 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 Auditory Verbal Learning Test 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 24, with higher scores indicating better outcomes.

    From preoperative to one month postoperative

  • Digital Span Test

    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 Digital Span Test 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 Digital Span Test 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 5 and a maximum value of 22, with higher scores indicating better outcomes.

    From preoperative to one month postoperative

  • Digital Order Test

    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 Digital Order Test 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 Digital Order Test 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 12, with higher scores indicating better outcomes.

    From preoperative to one month postoperative

Study Arms (1)

Intraoperative and One month after the operation microelectrode stimulation of DBS

EXPERIMENTAL

By comparing the behavioral characteristics of the memory paradigm under microelectrode stimulation during DBS operation and the characteristics of the electrophysiological signals behind it, as well as the behavioral characteristics of the memory paradigm under electrical stimulation and the characteristics of brain network activity during DBS startup one month after surgery, we analyzed the regulatory effect of substantia nigra DBS on memory network

Device: microelectrode stimulation of DBS

Interventions

microelectrode stimulation of DBSDEVICE

Contact 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

Intraoperative and One month after the operation microelectrode stimulation of DBS

Eligibility Criteria

Age50 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Beijing Tiantan Hospital

Beijing, Beijing Municipality, 100071, China

RECRUITING

MeSH Terms

Conditions

Parkinson DiseaseParkinsonian DisordersCognitive Dysfunction

Condition Hierarchy (Ancestors)

Basal Ganglia DiseasesBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesMovement DisordersSynucleinopathiesNeurodegenerative DiseasesCognition DisordersNeurocognitive DisordersMental Disorders

Study Officials

  • lin shi, M.D.

    Beijing Tiantan Hospital

    STUDY CHAIR

Central Study Contacts

lin shi, M.D.

CONTACT

008615210466780shilin2015@foxmail.com

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Model Details: By comparing the behavioral characteristics of the memory paradigm under microelectrode stimulation during DBS operation and the characteristics of the electrophysiological signals behind it, as well as the behavioral characteristics of the memory paradigm under electrical stimulation and the characteristics of brain network activity during DBS startup one month after surgery, we analyzed the regulatory effect of substantia nigra DBS on memory network
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 11, 2024

First Posted

May 6, 2024

Study Start

July 1, 2024

Primary Completion

December 31, 2025

Study Completion (Estimated)

December 31, 2026

Last Updated

May 31, 2025

Record last verified: 2025-05

Locations

CN(1)