xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05971030</url>
    </required_header>
    <id_info>
      <org_study_id>2023062</org_study_id>
      <nct_id>NCT05971030</nct_id>
    </id_info>
    <brief_title>Clinical Exploratory Research of Medial Prefrontal Cortex Combined With Dorsolateral Prefrontal Cortex Electrical Stimulation in the Treatment of Alzheimer's Disease</brief_title>
    <acronym>CBS-m/dlPFC-AD</acronym>
    <official_title>Clinical Exploratory Research of Medial Prefrontal Cortex Combined With Dorsolateral Prefrontal Cortex Electrical Stimulation in the Treatment of Alzheimer's Disease</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Xuanwu Hospital, Beijing</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Xuanwu Hospital, Beijing</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Alzheimer's disease (AD) is a common neurodegenerative disease characterized by progressive&#xD;
        cognitive impairment and memory impairment, and is also a major cause of global dementia,&#xD;
        characterized by progressive decline in memory and daily living behavior. The incidence rate&#xD;
        of AD increases with age. The prevalence rate of AD among men over 65 years old in China is&#xD;
        3.4%, and that of women is 7.7%, with a total prevalence rate of 5.9%. Among them, people&#xD;
        over 65 years old can live for an average of 4 to 8 years after being diagnosed with&#xD;
        Alzheimer's disease. According to statistics, there were approximately 5.98 million AD&#xD;
        patients in China in 2005, reaching 10.2 million in 2020 and 22.5 million by 2040, making it&#xD;
        the largest country with AD.&#xD;
  &#xD;
        At present, the treatment of AD is mostly limited to drug therapy, including Acetylcholine&#xD;
        enzyme inhibitor, N-methyl-D-aspartate receptor antagonist and brain cell metabolism&#xD;
        promoter. Although there are many types of drugs, their efficacy is not satisfactory, as they&#xD;
        not only cannot effectively prevent and cure AD, but also cannot slow down the progression of&#xD;
        AD. Regarding the surgical treatment of AD, neuromodulatory surgery, especially DBS (Deep&#xD;
        Brain Electrical Stimulation), involves implanting stimulation electrodes into deep neural&#xD;
        nuclei in the brain and performing electrical stimulation to change the excitability of the&#xD;
        corresponding nuclei or neural circuits, and has been included in alternative treatment&#xD;
        plans. In the past 20 years, DBS technology has been continuously explored for the treatment&#xD;
        of AD, but an increasing number of clinical trials have shown that there is no effective&#xD;
        target for AD-DBS. Therefore, there is an urgent need for new treatment methods to improve&#xD;
        the current treatment status.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        The main principle of DBS is to regulate the activity of neural components by implanting&#xD;
        electrodes into key brain regions using a built-in pulse generator. The basic principle of&#xD;
        using DBS in AD is that AD is not only a neurodegenerative disease, but also a neural circuit&#xD;
        disease, because it affects several integrated cortical and subcortical pathways, especially&#xD;
        those involving memory and cognition. DBS implants stimulation electrodes into deep neural&#xD;
        nuclei in the brain for electrical stimulation, altering the excitability of the&#xD;
        corresponding nuclei or neural circuits, which may lead to therapeutic effects. However, the&#xD;
        stimulation targets of the electrodes are still unclear.&#xD;
  &#xD;
        There are currently 3 clinical studies on AD-DBS reported in the literature, using&#xD;
        stimulation targets such as the Basal Nucleus of Meynert (NBM) and the fornix. One of the&#xD;
        studies was reported this year by a team from Kuhn et al. in Germany. They used NBM as a&#xD;
        stimulation target and treated 6 patients with DBS. The stimulation lasted for 12 months and&#xD;
        was evaluated using the Alzheimer's Disease Assessment Scale - Cognitive Scale (ADAS Co g)&#xD;
        and the Simplified Mental State Examination Scale (MMSE). Among them, one patient showed&#xD;
        improvement in their ADAS Log score, two patients stabilized, and three patients continued to&#xD;
        deteriorate in cognitive function. The other was a phase I clinical trial conducted by the&#xD;
        Lozano team in Canada in 2010. The team used the fornix as a stimulation target to perform&#xD;
        DBS treatment on 6 mild AD patients, with the same stimulation for 12 months. The results&#xD;
        showed that only 1 out of 6 patients had significant improvement in cognitive function&#xD;
        (reduced ADAS Cog score), while the remaining 5 patients still showed varying degrees of&#xD;
        deterioration. In addition, Fontaine et al. reported in 2013 on a patient with transfornix&#xD;
        electrical stimulation, where 12 months of continuous electrical stimulation stabilized the&#xD;
        patient's MMSE and ADAS-Log scores. However, the above three studies all found that DBS can&#xD;
        improve the glucose metabolism level of brain tissues in temporal and parietal lobes. The&#xD;
        above studies indicate that although NBM and fornix electrical stimulation have some&#xD;
        improvement in cognitive function in some AD patients, the overall improvement rate is low,&#xD;
        with most patients in an unresponsive state. Therefore, given the core position of&#xD;
        stimulation targets in deep brain electrical stimulation surgery, it is urgent to explore new&#xD;
        stimulation targets in order to improve the efficacy of DBS. The combination of medial&#xD;
        prefrontal cortex (mPFC) and dorsolateral prefrontal cortex (dlPFC) can serve as an ideal&#xD;
        stimulation target At present, the treatment of AD is still a global challenge, but the&#xD;
        non-invasive neural regulation techniques (rTMS and tDCS) based on the medial prefrontal&#xD;
        cortex (mPFC) and dorsolateral prefrontal cortex (dlPFC) have preliminarily confirmed that&#xD;
        mPFC and dlPFC regions may be potential therapeutic targets for AD, which can significantly&#xD;
        improve the cognitive status of therapists. At present, the targets used for treating AD with&#xD;
        DBS are the fornix and NBM, but the effectiveness of treating AD has not been confirmed.&#xD;
        Based on a thorough analysis of current international research and in conjunction with&#xD;
        previous research conducted by our center, the investigators propose to combine the left mPFC&#xD;
        and dlPFC regions as stimulation targets and innovatively use sheet electrodes for cortical&#xD;
        brain stimulation (CBS), which is well established. As a stimulation method of DBS, CBS&#xD;
        stimulates the cortex relative to the deep stimulation target. For example, common pain&#xD;
        electrical stimulation uses CBS, so the cortical electrical stimulation in this study adopts&#xD;
        the naming method of CBS. On this basis, the investigators strictly set inclusion and&#xD;
        exclusion criteria to ensure the quality of enrolled patients, and conducted thorough&#xD;
        experimental design and validated the efficacy of CBS in treating AD from multiple&#xD;
        perspectives using specific memory and cognitive function assessment scales, fusion function,&#xD;
        structure, metabolic brain networks, and other methods.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">July 30, 2023</start_date>
    <completion_date type="Anticipated">July 30, 2025</completion_date>
    <primary_completion_date type="Anticipated">May 30, 2025</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>N/A</allocation>
      <intervention_model>Single Group Assignment</intervention_model>
      <intervention_model_description>case series</intervention_model_description>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Auditory verbal learning test (AVLT) before and after DBS</measure>
      <time_frame>1 months before DBS, 1 month, 2 months, 3 months, 6 months, and 12 months after DBS.</time_frame>
      <description>ALVT will be performed before and after DBS operations to examine the AD. patients' ability.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Mini-mental State Examination (MMSE) before and after DBS</measure>
      <time_frame>1 months before DBS, 1 month, 2 months, 3 months, 6 months, and 12 months after DBS.</time_frame>
      <description>MMSE will be performed before and after DBS operations to examine the AD.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-COG)</measure>
      <time_frame>1 months before DBS, 1 month, 2 months, 3 months, 6 months, and 12 months after DBS.</time_frame>
      <description>ADAS-COG will be performed before and after DBS operations to examine the AD.</description>
    </secondary_outcome>
    <number_of_arms>1</number_of_arms>
    <enrollment type="Anticipated">3</enrollment>
    <condition>Alzheimer Disease</condition>
    <condition>Electric Stimulation Therapy</condition>
    <arm_group>
      <arm_group_label>CBS for mPFC and dlPFC</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Case series of AD patients who accept CBS for mPFC and dlPFC</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Cortical brain stimulation of mPFC and dlPFC</intervention_name>
      <description>Left medial prefrontal cortex combined with dorsolateral prefrontal cortex electrical stimulation</description>
      <arm_group_label>CBS for mPFC and dlPFC</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Male or female aged 40 to 70;&#xD;
  &#xD;
            2. eets the diagnostic criteria for mild to moderate AD;&#xD;
  &#xD;
            3. A CDR score of 0.5 or 1.0;&#xD;
  &#xD;
            4. The MMSE score is between 18 and 28;&#xD;
  &#xD;
            5. Regularly taking cholinesterase inhibitors for more than 6 months&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Existence of brain structural abnormalities (such as brain tumors, cerebral&#xD;
               infarction, and intracranial hematoma);&#xD;
  &#xD;
            2. Suffering from other neurological or psychiatric diseases;&#xD;
  &#xD;
            3. Accompanying comorbidities that are not suitable for surgical treatment;&#xD;
  &#xD;
            4. Individuals with contraindications for MRI or PET testing&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>40 Years</minimum_age>
      <maximum_age>70 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Yuqing Zhang</last_name>
      <phone>83198930</phone>
      <email>yuqzhang@vip.163.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Yan Yin</last_name>
      <phone>83198930</phone>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Xuanwu Hospital</name>
        <address>
          <city>Beijing</city>
          <country>China</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Yuqing Zhang</last_name>
        <phone>13701373585</phone>
        <email>yuqzhang@vip.163.com</email>
      </contact>
    </location>
    <location_countries>
      <country>China</country>
    </location_countries>
    <verification_date>June 2023</verification_date>
    <study_first_submitted>July 20, 2023</study_first_submitted>
    <study_first_submitted_qc>July 30, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 2, 2023</study_first_posted>
    <last_update_submitted>July 30, 2023</last_update_submitted>
    <last_update_submitted_qc>July 30, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 2, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Alzheimer Disease</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>We will publish our results once the study finished</ipd_description>
      <ipd_info_type>Clinical Study Report (CSR)</ipd_info_type>
      <ipd_time_frame>after the study finished</ipd_time_frame>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05971030
  org study id: 2023062
  nct id: NCT05971030
  lead sponsor: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  Alzheimer's disease (AD) is a common neurodegenerative disease characterized by progressive
        cognitive impairment and memory impairment, and is also a major cause of global dementia,
        characterized by progressive decline in memory and daily living behavior. The incidence rate
        of AD increases with age. The prevalence rate of AD among men over 65 years old in China is
        3.4%, and that of women is 7.7%, with a total prevalence rate of 5.9%. Among them, people
        over 65 years old can live for an average of 4 to 8 years after being diagnosed with
        Alzheimer's disease. According to statistics, there were approximately 5.98 million AD
        patients in China in 2005, reaching 10.2 million in 2020 and 22.5 million by 2040, making it
        the largest country with AD.
  
        At present, the treatment of AD is mostly limited to drug therapy, including Acetylcholine
        enzyme inhibitor, N-methyl-D-aspartate receptor antagonist and brain cell metabolism
        promoter. Although there are many types of drugs, their efficacy is not satisfactory, as they
        not only cannot effectively prevent and cure AD, but also cannot slow down the progression of
        AD. Regarding the surgical treatment of AD, neuromodulatory surgery, especially DBS (Deep
        Brain Electrical Stimulation), involves implanting stimulation electrodes into deep neural
        nuclei in the brain and performing electrical stimulation to change the excitability of the
        corresponding nuclei or neural circuits, and has been included in alternative treatment
        plans. In the past 20 years, DBS technology has been continuously explored for the treatment
        of AD, but an increasing number of clinical trials have shown that there is no effective
        target for AD-DBS. Therefore, there is an urgent need for new treatment methods to improve
        the current treatment status.
  The main principle of DBS is to regulate the activity of neural components by implanting
        electrodes into key brain regions using a built-in pulse generator. The basic principle of
        using DBS in AD is that AD is not only a neurodegenerative disease, but also a neural circuit
        disease, because it affects several integrated cortical and subcortical pathways, especially
        those involving memory and cognition. DBS implants stimulation electrodes into deep neural
        nuclei in the brain for electrical stimulation, altering the excitability of the
        corresponding nuclei or neural circuits, which may lead to therapeutic effects. However, the
        stimulation targets of the electrodes are still unclear.
  
        There are currently 3 clinical studies on AD-DBS reported in the literature, using
        stimulation targets such as the Basal Nucleus of Meynert (NBM) and the fornix. One of the
        studies was reported this year by a team from Kuhn et al. in Germany. They used NBM as a
        stimulation target and treated 6 patients with DBS. The stimulation lasted for 12 months and
        was evaluated using the Alzheimer's Disease Assessment Scale - Cognitive Scale (ADAS Co g)
        and the Simplified Mental State Examination Scale (MMSE). Among them, one patient showed
        improvement in their ADAS Log score, two patients stabilized, and three patients continued to
        deteriorate in cognitive function. The other was a phase I clinical trial conducted by the
        Lozano team in Canada in 2010. The team used the fornix as a stimulation target to perform
        DBS treatment on 6 mild AD patients, with the same stimulation for 12 months. The results
        showed that only 1 out of 6 patients had significant improvement in cognitive function
        (reduced ADAS Cog score), while the remaining 5 patients still showed varying degrees of
        deterioration. In addition, Fontaine et al. reported in 2013 on a patient with transfornix
        electrical stimulation, where 12 months of continuous electrical stimulation stabilized the
        patient's MMSE and ADAS-Log scores. However, the above three studies all found that DBS can
        improve the glucose metabolism level of brain tissues in temporal and parietal lobes. The
        above studies indicate that although NBM and fornix electrical stimulation have some
        improvement in cognitive function in some AD patients, the overall improvement rate is low,
        with most patients in an unresponsive state. Therefore, given the core position of
        stimulation targets in deep brain electrical stimulation surgery, it is urgent to explore new
        stimulation targets in order to improve the efficacy of DBS. The combination of medial
        prefrontal cortex (mPFC) and dorsolateral prefrontal cortex (dlPFC) can serve as an ideal
        stimulation target At present, the treatment of AD is still a global challenge, but the
        non-invasive neural regulation techniques (rTMS and tDCS) based on the medial prefrontal
        cortex (mPFC) and dorsolateral prefrontal cortex (dlPFC) have preliminarily confirmed that
        mPFC and dlPFC regions may be potential therapeutic targets for AD, which can significantly
        improve the cognitive status of therapists. At present, the targets used for treating AD with
        DBS are the fornix and NBM, but the effectiveness of treating AD has not been confirmed.
        Based on a thorough analysis of current international research and in conjunction with
        previous research conducted by our center, the investigators propose to combine the left mPFC
        and dlPFC regions as stimulation targets and innovatively use sheet electrodes for cortical
        brain stimulation (CBS), which is well established. As a stimulation method of DBS, CBS
        stimulates the cortex relative to the deep stimulation target. For example, common pain
        electrical stimulation uses CBS, so the cortical electrical stimulation in this study adopts
        the naming method of CBS. On this basis, the investigators strictly set inclusion and
        exclusion criteria to ensure the quality of enrolled patients, and conducted thorough
        experimental design and validated the efficacy of CBS in treating AD from multiple
        perspectives using specific memory and cognitive function assessment scales, fusion function,
        structure, metabolic brain networks, and other methods.
  allocation: N/A
  intervention model: Single Group Assignment
  intervention model description: case series
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Auditory verbal learning test (AVLT) before and after DBS
  time frame: 1 months before DBS, 1 month, 2 months, 3 months, 6 months, and 12 months after DBS.
  description: ALVT will be performed before and after DBS operations to examine the AD. patients' ability.
  measure: Mini-mental State Examination (MMSE) before and after DBS
  time frame: 1 months before DBS, 1 month, 2 months, 3 months, 6 months, and 12 months after DBS.
  description: MMSE will be performed before and after DBS operations to examine the AD.
  measure: Alzheimer's Disease Assessment Scale - Cognitive Subscale (ADAS-COG)
  time frame: 1 months before DBS, 1 month, 2 months, 3 months, 6 months, and 12 months after DBS.
  description: ADAS-COG will be performed before and after DBS operations to examine the AD.
  arm group label: CBS for mPFC and dlPFC
  arm group type: Experimental
  description: Case series of AD patients who accept CBS for mPFC and dlPFC
  intervention type: Device
  intervention name: Cortical brain stimulation of mPFC and dlPFC
  description: Left medial prefrontal cortex combined with dorsolateral prefrontal cortex electrical stimulation
  arm group label: CBS for mPFC and dlPFC
  criteria: 
  gender: All
  minimum age: 40 Years
  maximum age: 70 Years
  healthy volunteers: No
  last name: Yuqing Zhang
  phone: 83198930
  email: yuqzhang@vip.163.com
  last name: Yan Yin
  phone: 83198930
  facility: 
  status: Recruiting
  contact: 
  country: China
  responsible party type: Sponsor
  mesh term: Alzheimer Disease
  sharing ipd: Yes
  ipd description: We will publish our results once the study finished
  ipd info type: Clinical Study Report (CSR)
  ipd time frame: after the study finished