<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/NCT03260257</url>
  </required_header>
  <id_info>
    <org_study_id>171020</org_study_id>
    <nct_id>NCT03260257</nct_id>
  </id_info>
  <brief_title>A Neurofeedback Intervention to Improve Working Memory in Schizophrenia</brief_title>
  <official_title>Enhancing Gamma Band Response in Schizophrenia to Improve Working</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Diego</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Diego</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>
      Schizophrenia affects 2.4 million Americans and causes significant individual and societal&#xD;
      costs. Cognitive deficits including poor working memory arise early in the course of illness,&#xD;
      account for poor long-term outcomes and have been difficult to treat with available&#xD;
      treatments. The investigators are proposing to develop a novel, computer-based brain training&#xD;
      to improve working memory in schizophrenia patients, which, if successful could have&#xD;
      significant personal, societal, and economic impact.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Schizophrenia (SCZ) is a chronic debilitating mental disorder that affects 2.4 million&#xD;
      Americans and leads to considerable individual and societal costs. In patients with SCZ,&#xD;
      cognitive deficits (CD) occur early in the course of the illness, are associated with more&#xD;
      severe illness, and are the best predictor of functional outcomes. Nonetheless, to date, CD&#xD;
      have been difficult to treat using available treatments. Recent studies suggest CD in&#xD;
      patients with SCZ may arise from abnormal synchronization of distributed neural networks.&#xD;
      Synchronization or synchronous firing of neurons, binds cortical areas into functional&#xD;
      networks in a task and state-dependent manner. Thus novel therapies that improve abnormal&#xD;
      neural synchrony may improve previously refractory symptoms arising from disordered brain&#xD;
      networks.&#xD;
&#xD;
      Neural synchrony or coherence in the gamma band (GBR, 30-45Hz) plays a central role in&#xD;
      top-down attention, multisensory processing, perceptual binding and working memory (WM).&#xD;
      Patients with SCZ exhibit abnormal GBR, and the magnitude of impairment is associated with&#xD;
      the severity of cognitive disorganization. Given these results, improving GBR should improve&#xD;
      CD, including WM in SCZ. This hypothesis has been tested and confirmed using repetitive&#xD;
      transcranial magnetic stimulation (rTMS). Additionally, EEG-based neurofeedback (NFB) is&#xD;
      hypothesized to improve GBR and cognitive function in patients with SCZ. NFB is a low-cost,&#xD;
      easily administered and well-tolerated treatment. In healthy controls, Gamma-NFB improves GBR&#xD;
      and cognitive function including WM. Thus, the investigators propose testing the feasibility&#xD;
      and effectiveness of improving GBR using gamma-NFB in patients with SCZ using the framework&#xD;
      of the R61/R33 mechanism.&#xD;
&#xD;
      The first trial (R61) is a proof-of-concept study designed to assess target engagement and&#xD;
      dose response curve. Thirty SCZ patients will receive G-NFB training for 12 weeks (2 weekly&#xD;
      sessions of 30minute duration) and be assessed for 1) evidence of training, 2) Change in GBR,&#xD;
      3) Change in WM and 4) Change in community functioning. The second trial (R33) aims to&#xD;
      confirm target engagement based on training parameters obtained from R61, and to assess&#xD;
      whether G-NFB is superior to an active-placebo neurofeedback intervention in improving GBR,&#xD;
      WM and community functioning.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">March 1, 2018</start_date>
  <completion_date type="Anticipated">December 30, 2023</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2023</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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Task related Gamma band response (gamma coherence and power)</measure>
    <time_frame>This variable will be assessed at t=0, 4 weeks, 8 weeks, 12 weeks and 4 weeks post completion of intervention</time_frame>
    <description>Gamma-NFBs effects on gamma coherence and gamma power over time will be assessed.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Working memory</measure>
    <time_frame>This variable will be assessed at t=0, 12 weeks, and 4 weeks post study completion.</time_frame>
    <description>Gamma-NFBs effects on non-verbal working memory will be assessed over time.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">80</enrollment>
  <condition>Schizophrenia</condition>
  <arm_group>
    <arm_group_label>Schizophrenia patients</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Thirty SCZ patients will receive neurofeedback to enhance gamma band response in an open-label, proof of concept study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Neurofeedback</intervention_name>
    <description>Neurofeedback (NFB) will be administered to improve gamma band response. NFBs effects will be measured on gamma coherence and working memory.</description>
    <arm_group_label>Schizophrenia patients</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of schizophrenia/schizoaffective disorder&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Active substance use disorders in the last 30 days&#xD;
&#xD;
          -  Medication changes in the last 30 days&#xD;
&#xD;
          -  History of traumatic brain injury&#xD;
&#xD;
          -  seizure disorder&#xD;
&#xD;
          -  pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Beverly Castillo, BS</last_name>
    <phone>858-267-2257</phone>
    <email>b1castillo@health.ucsd.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Fiza Singh, MD</last_name>
    <phone>858-922-4365</phone>
    <email>fsingh@health.ucsd.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>University of California at San Diego</name>
      <address>
        <city>La Jolla</city>
        <state>California</state>
        <zip>92093</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Fiza Singh, MD</last_name>
      <phone>858-922-4365</phone>
      <email>fsingh@ucsd.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>August 17, 2017</study_first_submitted>
  <study_first_submitted_qc>August 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 24, 2017</study_first_posted>
  <last_update_submitted>May 8, 2023</last_update_submitted>
  <last_update_submitted_qc>May 8, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of California, San Diego</investigator_affiliation>
    <investigator_full_name>Fiza Singh</investigator_full_name>
    <investigator_title>Assistant Clinical Professor</investigator_title>
  </responsible_party>
  <keyword>Neurofeedback, Gamma band response</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</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/NCT03260257
org study id: 171020
nct id: NCT03260257
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Schizophrenia affects 2.4 million Americans and causes significant individual and societal
      costs. Cognitive deficits including poor working memory arise early in the course of illness,
      account for poor long-term outcomes and have been difficult to treat with available
      treatments. The investigators are proposing to develop a novel, computer-based brain training
      to improve working memory in schizophrenia patients, which, if successful could have
      significant personal, societal, and economic impact.
Schizophrenia (SCZ) is a chronic debilitating mental disorder that affects 2.4 million
      Americans and leads to considerable individual and societal costs. In patients with SCZ,
      cognitive deficits (CD) occur early in the course of the illness, are associated with more
      severe illness, and are the best predictor of functional outcomes. Nonetheless, to date, CD
      have been difficult to treat using available treatments. Recent studies suggest CD in
      patients with SCZ may arise from abnormal synchronization of distributed neural networks.
      Synchronization or synchronous firing of neurons, binds cortical areas into functional
      networks in a task and state-dependent manner. Thus novel therapies that improve abnormal
      neural synchrony may improve previously refractory symptoms arising from disordered brain
      networks.

      Neural synchrony or coherence in the gamma band (GBR, 30-45Hz) plays a central role in
      top-down attention, multisensory processing, perceptual binding and working memory (WM).
      Patients with SCZ exhibit abnormal GBR, and the magnitude of impairment is associated with
      the severity of cognitive disorganization. Given these results, improving GBR should improve
      CD, including WM in SCZ. This hypothesis has been tested and confirmed using repetitive
      transcranial magnetic stimulation (rTMS). Additionally, EEG-based neurofeedback (NFB) is
      hypothesized to improve GBR and cognitive function in patients with SCZ. NFB is a low-cost,
      easily administered and well-tolerated treatment. In healthy controls, Gamma-NFB improves GBR
      and cognitive function including WM. Thus, the investigators propose testing the feasibility
      and effectiveness of improving GBR using gamma-NFB in patients with SCZ using the framework
      of the R61/R33 mechanism.

      The first trial (R61) is a proof-of-concept study designed to assess target engagement and
      dose response curve. Thirty SCZ patients will receive G-NFB training for 12 weeks (2 weekly
      sessions of 30minute duration) and be assessed for 1) evidence of training, 2) Change in GBR,
      3) Change in WM and 4) Change in community functioning. The second trial (R33) aims to
      confirm target engagement based on training parameters obtained from R61, and to assess
      whether G-NFB is superior to an active-placebo neurofeedback intervention in improving GBR,
      WM and community functioning.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Task related Gamma band response (gamma coherence and power)
time frame: This variable will be assessed at t=0, 4 weeks, 8 weeks, 12 weeks and 4 weeks post completion of intervention
description: Gamma-NFBs effects on gamma coherence and gamma power over time will be assessed.
measure: Change in Working memory
time frame: This variable will be assessed at t=0, 12 weeks, and 4 weeks post study completion.
description: Gamma-NFBs effects on non-verbal working memory will be assessed over time.
arm group label: Schizophrenia patients
arm group type: Experimental
description: Thirty SCZ patients will receive neurofeedback to enhance gamma band response in an open-label, proof of concept study.
intervention type: Other
intervention name: Neurofeedback
description: Neurofeedback (NFB) will be administered to improve gamma band response. NFBs effects will be measured on gamma coherence and working memory.
arm group label: Schizophrenia patients
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Beverly Castillo, BS
phone: 858-267-2257
email: b1castillo@health.ucsd.edu
last name: Fiza Singh, MD
phone: 858-922-4365
email: fsingh@health.ucsd.edu
facility: 
status: Recruiting
contact: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of California, San Diego
investigator full name: Fiza Singh
investigator title: Assistant Clinical Professor
mesh term: Schizophrenia
sharing ipd: No