<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/NCT03756610</url>
  </required_header>
  <id_info>
    <org_study_id>2018-24</org_study_id>
    <nct_id>NCT03756610</nct_id>
  </id_info>
  <brief_title>Transcranial Alternating Current Stimulation (tACS) for Cognitive Impairments in Patients With Schizophrenia</brief_title>
  <official_title>Transcranial Alternating Current Stimulation (tACS) for Cognitive Impairments in Patients With Schizophrenia: a Randomized Controlled Trial</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shanghai Mental Health Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Shanghai Mental Health Center</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>
      This trial attempts to investigate whether 10 sessions of tACS improves cognitive function,&#xD;
      especially which domains of cognitive function are most improved and to investigate whether&#xD;
      10 sessions of tACS affecting brain activation during a working memory task and changes&#xD;
      patterns of brain connectivity networks.Subjects will be divided into 2 groups 2:1, active&#xD;
      and sham tACS. 50 subjects will be in the active group, and 25 subjects in the sham group&#xD;
      (specific numbers to be decided on later).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Schizophrenia patients (SZ) show profound and persistent cognitive deficits in attention,&#xD;
      executive processing, and verbal and visuospatial memory, which persist even after psychotic&#xD;
      symptoms are ameliorated. Cognitive deficits may be more important in preventing functional,&#xD;
      occupational, and social recovery in SZ than other symptom domains and are not effectively&#xD;
      treated by current pharmacological approaches. Alternating current stimulation (tACS) is less&#xD;
      expensive than other modalities (e.g. repetitive transcranial magnetic stimulation; rTMS),&#xD;
      easily available, and has a good safety profile in healthy controls (HC) and SZ. The ability&#xD;
      to entrain γ oscillations with 40Hz tACS, might compensate more specifically for this deficit&#xD;
      in γ oscillations in schizophrenia, and, may therefore, produce more robust behavioral&#xD;
      improvements in working memory and other aspects of cognition.However, no studies have looked&#xD;
      at the effects of multiple daily tACS stimulation at a 40HZ γ frequency on cognitive function&#xD;
      and symptoms in schizophrenia. This provides a rationale for the current study, which&#xD;
      proposes to investigate the effects of 10 sessions of 40HZ tACS on cognitive functions,&#xD;
      symptoms in schizophrenia.&#xD;
&#xD;
      Active vs. sham treatment will be randomly assigned in a 2:1 fashion (A:S) in groups using&#xD;
      computer generated lists. Subjects and tDCS testers or evaluators will be blind to treatment.&#xD;
      Subjects will be evaluated with cognitive, symptom and functional measures at baseline,&#xD;
      within 1 day ( or 2 days fro some measures) after 10 sessions, 2 weeks after 10 sessions, 1&#xD;
      month after 10 sessions, and 2 months after 10 sessions.After the 1 month evaluation,&#xD;
      subjects in the initial active tACS group will be randomly assigned to receive either 5&#xD;
      booster sessions of either active or sham tACS ( 25 subjects each), following parameters used&#xD;
      in the initial treatment. Subjects in the initial Sham group will receive 5 booster session&#xD;
      Sham tACS. Participants will be scanned once prior to tACS sessions, and within 3 days after&#xD;
      the 10th tACS session, using our Siemens 3T Tim Verio MRI scanner with a standard 32-channel&#xD;
      phased-array head coil.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Anticipated">November 2018</start_date>
  <completion_date type="Anticipated">March 2020</completion_date>
  <primary_completion_date type="Anticipated">December 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>changes in The MATRICS Consensus Cognitive Battery (MCCB)</measure>
    <time_frame>Change from Baseline MCCB at 2 weeks.</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>changes in Neuroimage changes in Magnetic Resonance Imaging (MRI)</measure>
    <time_frame>Change from Baseline at 2 weeks.</time_frame>
    <description>Including T1, resting state functional MRI, task based functional MRI and Diffusion Tensor Imaging(DTI)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>changes in Gamma oscillation intensity ( 40-80 Hz) over the left and right frontal lobe</measure>
    <time_frame>Change from Baseline at 2 weeks.</time_frame>
    <description>measured by electroencephalogram (EEG)</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>N-back task</measure>
    <time_frame>At baseline,1-week, 2-week, 4-week, and 8-week follow-up.</time_frame>
    <description>to test working memory</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Paced Auditory Serial Addition Task (PASAT)</measure>
    <time_frame>At baseline,2-week, 4-week, and 8-week follow-up.</time_frame>
    <description>to test Verbal Working memory</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The Positive and Negative Syndrome Scale (PANSS)</measure>
    <time_frame>At baseline,2-week, 4-week, and 8-week follow-up.</time_frame>
    <description>PANSS was assessed using 30 basic items to form three subscales: positive, negative, and general psychopathological scales.The value of each item is ranging from 1 to 7, higher values represent more serious symptoms of schizophrenia.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The USCD Performance- Based Skills Assessment Battery (UPSA)</measure>
    <time_frame>At baseline,2-week, 4-week, and 8-week follow-up.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Side-effects of tACS</measure>
    <time_frame>At each stimulation session,up to 2 weeks.</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The MATRICS Consensus Cognitive Battery (MCCB)</measure>
    <time_frame>At 4-week and 8-week follow-up.</time_frame>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">90</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>Active tACS &amp; active boosting group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>The active tACS &amp; active boosting group will be stimulated with 10 sessions of active alternating current stimulation (tACS) and 5 booster sessions of active tACS.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active tACS &amp; sham boosting group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>The active tACS &amp; sham boosting group will be stimulated with 10 sessions of active alternating current stimulation (tACS) and 5 booster sessions of sham tACS.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham tACS &amp; sham boosting group</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>The sham tACS &amp; sham boosting group will be stimulated with 10 sessions of sham alternating current stimulation (tACS) and 5 booster sessions of sham tACS.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active tACS</intervention_name>
    <description>Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded). Each subject will have 10 active tACS sessions.The active tACS group will be stimulated with a 2 mA current for 20 minutes.</description>
    <arm_group_label>Active tACS &amp; active boosting group</arm_group_label>
    <arm_group_label>Active tACS &amp; sham boosting group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham tACS</intervention_name>
    <description>Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded). Each subject will have 10 sham tACS sessions.The sham tACS group will have stimulation lasting only 40 seconds though the electrodes will remain in place for 20 min.</description>
    <arm_group_label>Sham tACS &amp; sham boosting group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active boosting</intervention_name>
    <description>Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded).One month later after initial treatment, each subject will have 5 booster sessions of active tACS.The active boosting group will be stimulated with a 2 mA current for 20 minutes.</description>
    <arm_group_label>Active tACS &amp; active boosting group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham boosting</intervention_name>
    <description>Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded).One month later after initial treatment, each subject will have 5 booster sessions of sham tACS.The sham boosting group will have stimulation lasting only 40 seconds though the electrodes will remain in place for 20 min.</description>
    <arm_group_label>Active tACS &amp; sham boosting group</arm_group_label>
    <arm_group_label>Sham tACS &amp; sham boosting group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects who have cognitive deficits as indicated by a score of &lt; 85 on RBANS, and&#xD;
             meet criteria for DSM-5 diagnosis of chronic SZ, schizoaffective disorder (SA), or&#xD;
             schizophreniform disorder (SZF), and who are stably treated with antipsychotic&#xD;
             medications and are not in acute exacerbation of illness symptoms.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with risk factors for an MRI scan, seizure disorder, and for women of&#xD;
             childbearing age who are pregnant or regularly engaging in sexual activity and not&#xD;
             regularly using an acceptable birth control method (systemic or double-barrier).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Chunbo Li, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shanghai Mental Health Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Chunbo Li, Ph.D.</last_name>
    <phone>86-21-34773243</phone>
    <email>chunbo_li@163.com</email>
  </overall_contact>
  <location>
    <facility>
      <name>Shanghai Mental Health Center</name>
      <address>
        <city>Shanghai</city>
        <state>Shanghai</state>
        <zip>200030</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Chunbo Li, PHD</last_name>
      <phone>86-21-34773243</phone>
      <email>chunbo_li@163.com</email>
    </contact>
    <investigator>
      <last_name>Chunbo Li, PHD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <verification_date>October 2018</verification_date>
  <study_first_submitted>October 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 26, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 28, 2018</study_first_posted>
  <last_update_submitted>November 26, 2018</last_update_submitted>
  <last_update_submitted_qc>November 26, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">November 28, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>tACS</keyword>
  <keyword>schizophrenia</keyword>
  <keyword>cognition</keyword>
  <keyword>fMRI</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT03756610
org study id: 2018-24
nct id: NCT03756610
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This trial attempts to investigate whether 10 sessions of tACS improves cognitive function,
      especially which domains of cognitive function are most improved and to investigate whether
      10 sessions of tACS affecting brain activation during a working memory task and changes
      patterns of brain connectivity networks.Subjects will be divided into 2 groups 2:1, active
      and sham tACS. 50 subjects will be in the active group, and 25 subjects in the sham group
      (specific numbers to be decided on later).
Schizophrenia patients (SZ) show profound and persistent cognitive deficits in attention,
      executive processing, and verbal and visuospatial memory, which persist even after psychotic
      symptoms are ameliorated. Cognitive deficits may be more important in preventing functional,
      occupational, and social recovery in SZ than other symptom domains and are not effectively
      treated by current pharmacological approaches. Alternating current stimulation (tACS) is less
      expensive than other modalities (e.g. repetitive transcranial magnetic stimulation; rTMS),
      easily available, and has a good safety profile in healthy controls (HC) and SZ. The ability
      to entrain γ oscillations with 40Hz tACS, might compensate more specifically for this deficit
      in γ oscillations in schizophrenia, and, may therefore, produce more robust behavioral
      improvements in working memory and other aspects of cognition.However, no studies have looked
      at the effects of multiple daily tACS stimulation at a 40HZ γ frequency on cognitive function
      and symptoms in schizophrenia. This provides a rationale for the current study, which
      proposes to investigate the effects of 10 sessions of 40HZ tACS on cognitive functions,
      symptoms in schizophrenia.

      Active vs. sham treatment will be randomly assigned in a 2:1 fashion (A:S) in groups using
      computer generated lists. Subjects and tDCS testers or evaluators will be blind to treatment.
      Subjects will be evaluated with cognitive, symptom and functional measures at baseline,
      within 1 day ( or 2 days fro some measures) after 10 sessions, 2 weeks after 10 sessions, 1
      month after 10 sessions, and 2 months after 10 sessions.After the 1 month evaluation,
      subjects in the initial active tACS group will be randomly assigned to receive either 5
      booster sessions of either active or sham tACS ( 25 subjects each), following parameters used
      in the initial treatment. Subjects in the initial Sham group will receive 5 booster session
      Sham tACS. Participants will be scanned once prior to tACS sessions, and within 3 days after
      the 10th tACS session, using our Siemens 3T Tim Verio MRI scanner with a standard 32-channel
      phased-array head coil.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: changes in The MATRICS Consensus Cognitive Battery (MCCB)
time frame: Change from Baseline MCCB at 2 weeks.
measure: changes in Neuroimage changes in Magnetic Resonance Imaging (MRI)
time frame: Change from Baseline at 2 weeks.
description: Including T1, resting state functional MRI, task based functional MRI and Diffusion Tensor Imaging(DTI)
measure: changes in Gamma oscillation intensity ( 40-80 Hz) over the left and right frontal lobe
time frame: Change from Baseline at 2 weeks.
description: measured by electroencephalogram (EEG)
measure: N-back task
time frame: At baseline,1-week, 2-week, 4-week, and 8-week follow-up.
description: to test working memory
measure: The Paced Auditory Serial Addition Task (PASAT)
time frame: At baseline,2-week, 4-week, and 8-week follow-up.
description: to test Verbal Working memory
measure: The Positive and Negative Syndrome Scale (PANSS)
time frame: At baseline,2-week, 4-week, and 8-week follow-up.
description: PANSS was assessed using 30 basic items to form three subscales: positive, negative, and general psychopathological scales.The value of each item is ranging from 1 to 7, higher values represent more serious symptoms of schizophrenia.
measure: The USCD Performance- Based Skills Assessment Battery (UPSA)
time frame: At baseline,2-week, 4-week, and 8-week follow-up.
measure: Side-effects of tACS
time frame: At each stimulation session,up to 2 weeks.
measure: The MATRICS Consensus Cognitive Battery (MCCB)
time frame: At 4-week and 8-week follow-up.
arm group label: Active tACS & active boosting group
arm group type: Active Comparator
description: The active tACS & active boosting group will be stimulated with 10 sessions of active alternating current stimulation (tACS) and 5 booster sessions of active tACS.
arm group label: Active tACS & sham boosting group
arm group type: Other
description: The active tACS & sham boosting group will be stimulated with 10 sessions of active alternating current stimulation (tACS) and 5 booster sessions of sham tACS.
arm group label: Sham tACS & sham boosting group
arm group type: Sham Comparator
description: The sham tACS & sham boosting group will be stimulated with 10 sessions of sham alternating current stimulation (tACS) and 5 booster sessions of sham tACS.
intervention type: Device
intervention name: Active tACS
description: Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded). Each subject will have 10 active tACS sessions.The active tACS group will be stimulated with a 2 mA current for 20 minutes.
arm group label: Active tACS & active boosting group
arm group label: Active tACS & sham boosting group
intervention type: Device
intervention name: Sham tACS
description: Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded). Each subject will have 10 sham tACS sessions.The sham tACS group will have stimulation lasting only 40 seconds though the electrodes will remain in place for 20 min.
arm group label: Sham tACS & sham boosting group
intervention type: Device
intervention name: Active boosting
description: Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded).One month later after initial treatment, each subject will have 5 booster sessions of active tACS.The active boosting group will be stimulated with a 2 mA current for 20 minutes.
arm group label: Active tACS & active boosting group
intervention type: Device
intervention name: Sham boosting
description: Placement of stimuli electrodes will be: a) active electrode over the left DLPFC (F3), and b) reference electrode over the right parietal region (P2). The exact location of electrodes will be determined by the 10/20 EEG method with EEG cap. Subjects will have tACS sessions on consecutive days (weekends and holidays excluded).One month later after initial treatment, each subject will have 5 booster sessions of sham tACS.The sham boosting group will have stimulation lasting only 40 seconds though the electrodes will remain in place for 20 min.
arm group label: Active tACS & sham boosting group
arm group label: Sham tACS & sham boosting group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Chunbo Li, Ph.D.
role: Principal Investigator
affiliation: Shanghai Mental Health Center
last name: Chunbo Li, Ph.D.
phone: 86-21-34773243
email: chunbo_li@163.com
facility: 
status: Recruiting
contact: 
investigator: 
country: China
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Cognitive Dysfunction
sharing ipd: No