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/NCT06003036</url>
    </required_header>
    <id_info>
      <org_study_id>STUDY23050056</org_study_id>
      <secondary_id>R21MH134128</secondary_id>
      <nct_id>NCT06003036</nct_id>
    </id_info>
    <brief_title>Accelerated Transcranial Magnetic Stimulation for People With Schizophrenia Treated With Clozapine</brief_title>
    <official_title>Accelerated Neuromodulation of Prefrontal Circuitry During Clozapine Treatment</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Deepak Sarpal</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Institute of Mental Health (NIMH)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>University of Pittsburgh</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>Yes</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        In this study, the investigators will examine whether a type of repetitive transcranial&#xD;
        magnetic stimulation called accelerated intermittent theta burst stimulation (iTBS) can&#xD;
        augment neurocognition in individuals who receive treatment with clozapine. Following a&#xD;
        baseline evaluation and magnetic resonance imaging (MRI), participants will undergo a session&#xD;
        of iTBS +MRI and session of sham delivery + MRI. The order for these sessions will be blinded&#xD;
        and randomized. The investigators predict that accelerated iTBS will enhance neurocognition&#xD;
        relative to sham delivery.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">September 2025</completion_date>
    <primary_completion_date type="Anticipated">June 2025</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>Crossover Assignment</intervention_model>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>change in brain functional connectivity within the prefrontal cortex</measure>
      <time_frame>1 hour</time_frame>
      <description>Examine changes in left dorsolateral prefrontal cortex-basal forebrain functional connectivity following adjunctive accelerated intermittent theta burst stimulation (iTBS)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>change in activation of the working memory network</measure>
      <time_frame>1 hour</time_frame>
      <description>Examine whether accelerated intermittent theta burst stimulation (iTBS) is associated with functional magnetic resonance imaging (fMRI)-based changes in activation of the working memory network during AX-continuous performance task engagement</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>explore change in functional magnetic resonance imaging (fMRI) measures versus plasma n-desmethylclozapine/clozapine ratios</measure>
      <time_frame>1 month</time_frame>
      <description>In exploratory analyses we will compare change in dorsolateral prefrontal cortex-basal forebrain functional connectivity and change in working memory network activation in relation to plasma n-desmethylclozapine/clozapine ratios.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Schizophrenia</condition>
    <condition>Schizoaffective Disorder</condition>
    <arm_group>
      <arm_group_label>iTBS, then Sham</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Sham, then iTBS</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>sham stimulation</intervention_name>
      <description>sham delivery of transcranial magnetic stimulation</description>
      <arm_group_label>Sham, then iTBS</arm_group_label>
      <arm_group_label>iTBS, then Sham</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>transcranial magnetic stimulation</intervention_name>
      <description>accelerated intermittent theta burst stimulation</description>
      <arm_group_label>Sham, then iTBS</arm_group_label>
      <arm_group_label>iTBS, then Sham</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. A current Diagnostic and Statistical Manual of Mental Disorders 5 (DSM 5)-defined&#xD;
               diagnosis of schizophrenia or schizoaffective disorder&#xD;
  &#xD;
            2. age 18-50 years&#xD;
  &#xD;
            3. at least 4 months of clozapine treatment&#xD;
  &#xD;
            4. history of at least 2 failed antipsychotic trials&#xD;
  &#xD;
            5. competency and willingness to sign informed consent&#xD;
  &#xD;
            6. A clinically optimized dosage of clozapine, unchanged for at least 1 month, with a&#xD;
               minimum of 150 mg/day&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Serious neurologic or medical condition/treatment that impacts the brain&#xD;
  &#xD;
            2. a significant risk of suicidal or homicidal behavior&#xD;
  &#xD;
            3. cognitive or language limitations, or any other factor that would preclude subjects&#xD;
               providing informed consent&#xD;
  &#xD;
            4. pregnancy or postpartum (&lt;6 weeks after delivery or miscarriage)&#xD;
  &#xD;
            5. history of treatment with electroconvulsive therapy&#xD;
  &#xD;
            6. contraindications for magnetic resonance imaging (e.g., a pacemaker)&#xD;
  &#xD;
            7. Structured Clinical Interview for Diagnostic and Statistical Manual of Mental&#xD;
               Disorders 5 (DSM 5)-verified moderate or severe substance use disorder, including&#xD;
               alcohol use disorder&#xD;
  &#xD;
            8. seizure disorder or prior history of seizures on clozapine&#xD;
  &#xD;
            9. patients taking both bupropion and clozapine&#xD;
  &#xD;
           10. prior issues with intermittent theta burst stimulation/transcranial magnetic&#xD;
               stimulation administration&#xD;
  &#xD;
          Concomitant treatment with serotonin and norepinephrine reuptake inhibitors will be&#xD;
          examined on a case-by-case basis.&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>50 Years</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Deepak K Sarpal, M.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>University of Pittsburgh</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Tori Blazinski</last_name>
      <phone>412-246-5618</phone>
      <email>blazinskit2@upmc.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Deepak Sarpal</last_name>
      <email>sarpaldk@upmc.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>UPMC Western Psychiatric Hospital/University of Pittsburgh</name>
        <address>
          <city>Pittsburgh</city>
          <state>Pennsylvania</state>
          <zip>15213</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Tori Blazinski</last_name>
        <email>blazinskit2@upmc.edu</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>August 2023</verification_date>
    <study_first_submitted>August 8, 2023</study_first_submitted>
    <study_first_submitted_qc>August 14, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 21, 2023</study_first_posted>
    <last_update_submitted>August 25, 2023</last_update_submitted>
    <last_update_submitted_qc>August 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">August 29, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor-Investigator</responsible_party_type>
      <investigator_affiliation>University of Pittsburgh</investigator_affiliation>
      <investigator_full_name>Deepak Sarpal</investigator_full_name>
      <investigator_title>Assistant Professor</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Schizophrenia</mesh_term>
      <mesh_term>Psychotic Disorders</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>de-identified individual participant data to the National Institute of Mental Health (NIMH) data archive</ipd_description>
    </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/NCT06003036
  org study id: STUDY23050056
  secondary id: R21MH134128
  nct id: NCT06003036
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: Yes
  is us export: No
  In this study, the investigators will examine whether a type of repetitive transcranial
        magnetic stimulation called accelerated intermittent theta burst stimulation (iTBS) can
        augment neurocognition in individuals who receive treatment with clozapine. Following a
        baseline evaluation and magnetic resonance imaging (MRI), participants will undergo a session
        of iTBS +MRI and session of sham delivery + MRI. The order for these sessions will be blinded
        and randomized. The investigators predict that accelerated iTBS will enhance neurocognition
        relative to sham delivery.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Basic Science
  masking: Triple (Participant, Care Provider, Investigator)
  measure: change in brain functional connectivity within the prefrontal cortex
  time frame: 1 hour
  description: Examine changes in left dorsolateral prefrontal cortex-basal forebrain functional connectivity following adjunctive accelerated intermittent theta burst stimulation (iTBS)
  measure: change in activation of the working memory network
  time frame: 1 hour
  description: Examine whether accelerated intermittent theta burst stimulation (iTBS) is associated with functional magnetic resonance imaging (fMRI)-based changes in activation of the working memory network during AX-continuous performance task engagement
  measure: explore change in functional magnetic resonance imaging (fMRI) measures versus plasma n-desmethylclozapine/clozapine ratios
  time frame: 1 month
  description: In exploratory analyses we will compare change in dorsolateral prefrontal cortex-basal forebrain functional connectivity and change in working memory network activation in relation to plasma n-desmethylclozapine/clozapine ratios.
  arm group label: iTBS, then Sham
  arm group type: Experimental
  arm group label: Sham, then iTBS
  arm group type: Experimental
  intervention type: Device
  intervention name: sham stimulation
  description: sham delivery of transcranial magnetic stimulation
  arm group label: Sham, then iTBS
  arm group label: iTBS, then Sham
  intervention type: Device
  intervention name: transcranial magnetic stimulation
  description: accelerated intermittent theta burst stimulation
  arm group label: Sham, then iTBS
  arm group label: iTBS, then Sham
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 50 Years
  healthy volunteers: No
  last name: Deepak K Sarpal, M.D.
  role: Principal Investigator
  affiliation: University of Pittsburgh
  last name: Tori Blazinski
  phone: 412-246-5618
  email: blazinskit2@upmc.edu
  last name: Deepak Sarpal
  email: sarpaldk@upmc.edu
  facility: 
  contact: 
  country: United States
  responsible party type: Sponsor-Investigator
  investigator affiliation: University of Pittsburgh
  investigator full name: Deepak Sarpal
  investigator title: Assistant Professor
  mesh term: Schizophrenia
  mesh term: Psychotic Disorders
  sharing ipd: Yes
  ipd description: de-identified individual participant data to the National Institute of Mental Health (NIMH) data archive