<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/NCT04418011</url>
  </required_header>
  <id_info>
    <org_study_id>133/2019</org_study_id>
    <nct_id>NCT04418011</nct_id>
  </id_info>
  <brief_title>Neuromodulation of Social Cognitive Circuitry in People With Schizophrenia Spectrum Disorders</brief_title>
  <acronym>ModSoCCS</acronym>
  <official_title>Neuromodulation of Social Cognitive Circuitry in People With Schizophrenia Spectrum Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre for Addiction and Mental Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Feinstein Institutes for Medical Research</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>University of Maryland, College Park</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Centre for Addiction and Mental Health</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study, the investigators will be examining the effects of repetitive transcranial&#xD;
      magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS) on social&#xD;
      cognitive impairments in individuals with schizophrenia spectrum disorders. Participants will&#xD;
      be chosen by chance to receive either active rTMS stimulation, active iTBS stimulation, sham&#xD;
      rTMS, or sham iTBS. The investigators predict that active 10Hz and iTBS stimulation will&#xD;
      improve social cognitive impairments compared to sham stimulation. We aim to identify which&#xD;
      type of active stimulation is most effective at inducing changes social cognition brain&#xD;
      circuitry and secondarily which type of active stimulation is best tolerated and most&#xD;
      effective at inducing changes in social cognitive performance.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is a randomized, double blind, sham controlled study which aims to use repetitive&#xD;
      transcranial magnetic stimulation (rTMS), a form of neuromodulation, to target the neural&#xD;
      circuitry of social cognitive (SCog) impairments in people with Schizophrenia Spectrum&#xD;
      Disorders. We will randomize 60 people with SSDs to three groups: 20 to a conventional form&#xD;
      of rTMS (i.e. 10 Hz rTMS); 20 to intermittent theta burst stimulation (iTBS); and 20 to&#xD;
      either sham 10Hz rTMS stimulation or sham iTBS. We will determine whether these treatments&#xD;
      can change the functional connectivity of key SCog brain circuits by targeting a brain region&#xD;
      known as the dorsomedial prefrontal cortex (DMPFC). Since each person's anatomical and&#xD;
      functional brain profile is slightly different, we will optimize the orientation and location&#xD;
      of coil placement in each individual. Overall, our proposal follows a target engagement&#xD;
      framework, including specifics regarding testing brain stimulation parameters (i.e., rTMS vs.&#xD;
      iTBS) and individualizing coil placement for optimal targeting. We anticipate that active 10&#xD;
      Hz rTMS or iTBS will demonstrate target engagement compared to sham, and potentially&#xD;
      ameliorate SCog deficits in people with SSDs. Our primary goal is to identify which treatment&#xD;
      best induces change in SCog brain circuitry and secondarily which treatment is best tolerated&#xD;
      and induces changes in social cognitive performance.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">November 30, 2020</start_date>
  <completion_date type="Anticipated">May 1, 2023</completion_date>
  <primary_completion_date type="Anticipated">February 28, 2023</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>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in mentalizing brain network functional connectivity</measure>
    <time_frame>2 weeks</time_frame>
    <description>Measured using the empathic accuracy fMRI task</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Treatment Tolerability</measure>
    <time_frame>2 weeks</time_frame>
    <description>Measured using the Visual Analogue Scale for Pain (VAS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Tolerability</measure>
    <time_frame>2 weeks</time_frame>
    <description>Measured using proportion of participants that report headache</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Tolerability</measure>
    <time_frame>2 weeks</time_frame>
    <description>Measured using proportion of participants that report dizziness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Tolerability</measure>
    <time_frame>2 weeks</time_frame>
    <description>Measured using proportion of treatment related SAE's</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">60</enrollment>
  <condition>Schizophrenia</condition>
  <condition>Schizoaffective Disorder</condition>
  <condition>Schizophreniform Disorders</condition>
  <arm_group>
    <arm_group_label>Active 10 Hz rTMS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Active treatment will be targeted to an intensity that is 120% of the resting motor threshold. Stimulation will be delivered at 10 Hz according to conventional FDA-approved parameters (4 s on and 26 s off; 3000 pulses per session; total duration 37.5 mins) .</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active iTBS</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Active iTBS will be targeted to an intensity that is 120% of the resting motor threshold. Stimulation will be delivered in triplet 50 Hz bursts, repeated at 5 Hz; 2 seconds on and 8 seconds off; 600 pulses per session; total duration of 3 min 9 seconds.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham rTMS</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Sham stimulation will be delivered using the same stimulation parameters as either 10 Hz rTMS or iTBS.&#xD;
For both active and sham stimulation, TMS coil positioning for each individual will be optimized by combining participant fMRI data, meta-analytic functional analysis, electric field modelling, and real-time neuronavigation.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Repetitive Transcranial Magnetic Stimulation</intervention_name>
    <description>The present study aims to use both repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS), safe and effective forms of neuromodulation, to target the neural circuitry of social cognitive (SCog) impairments in people with SSDs. Treatment sessions will be administered five days per week for two weeks.&#xD;
Other Name: MagPro X100 or R30 (Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany)</description>
    <arm_group_label>Active 10 Hz rTMS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Repetitive Transcranial Magnetic Stimulation (Intermittent Theta Burst Stimulation)</intervention_name>
    <description>The present study aims to use both repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS), safe and effective forms of neuromodulation, to target the neural circuitry of social cognitive (SCog) impairments in people with SSDs. Treatment sessions will be administered five days per week for two weeks.&#xD;
Other Name: MagPro X100 or R30 (Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany)</description>
    <arm_group_label>Active iTBS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Repetitive Transcranial Magnetic Stimulation (Sham)</intervention_name>
    <description>Other Name: MagPro X100 or R30(Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany)</description>
    <arm_group_label>Sham rTMS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18-55 years;&#xD;
&#xD;
          2. Male or Female;&#xD;
&#xD;
          3. DSM-5 diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform&#xD;
             disorder (documented by SCID-5);&#xD;
&#xD;
          4. Prescription of antipsychotic medication for at least 60 days and constant dose for 30&#xD;
             days prior to study entry (either first or second generation antipsychotics&#xD;
             permitted);&#xD;
&#xD;
          5. Able to participate in the informed consent process and provide voluntary informed&#xD;
             consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. A history of a DSM-5 substance use disorder (other than caffeine, tobacco, or mild&#xD;
             cannabis use) within the past six months; or a positive baseline urine drug screen.&#xD;
&#xD;
          2. Type 1 diabetes mellitus (i.e., insulin-dependent diabetes mellitus with onset &lt; 35&#xD;
             years of age and/or diabetes mellitus that has been complicated by a prior documented&#xD;
             episode of ketoacidosis)&#xD;
&#xD;
          3. Acute or unstable medical illness (e.g. delirium, cancer, uncontrolled diabetes,&#xD;
             decompensated cardiac, hepatic, renal or pulmonary disease, stroke, or myocardial&#xD;
             infarction), whose pathology or treatment could alter the presentation or treatment of&#xD;
             schizophrenia or significantly increase the risk associated with the proposed&#xD;
             treatment protocol&#xD;
&#xD;
          4. Neurological disease associated with extrapyramidal signs and symptoms (e.g.&#xD;
             Parkinson's disease); epilepsy (i.e. seizures not due to medication/drugs or due to&#xD;
             fever) or physical signs of stroke; any diagnosis of a Central Nervous System (CNS)&#xD;
             disorder&#xD;
&#xD;
          5. Requires a benzodiazepine with a regular dose equivalent to lorazepam 2 mg/day or&#xD;
             higher or any anticonvulsant due to the potential of these medications to limit the&#xD;
             efficacy of rTMS&#xD;
&#xD;
          6. Suspected DSM-5 intellectual disability based upon clinical interview and psychosocial&#xD;
             history&#xD;
&#xD;
          7. Prior Psychosurgery&#xD;
&#xD;
          8. Presence of MRI contraindications (e.g. pacemakers)&#xD;
&#xD;
          9. Pregnancy&#xD;
&#xD;
         10. Prior history of rTMS treatment&#xD;
&#xD;
         11. Diagnosis of Intellectual Disability (i.e. IQ &lt;71)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Aristotle Voineskos, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre for Addiction and Mental Health</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Anil Malhotra, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Feinstein Institute for Medical Research, Zucker Hillside Hospital</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Robert Buchanan, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Maryland Psychiatric Research Centre, University of Maryland</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Aristotle Voineskos, MD</last_name>
    <phone>416-535-8501</phone>
    <phone_ext>34378</phone_ext>
    <email>aristotle.voineskos@camh.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Dielle Miranda, MA</last_name>
    <phone>416-535-8501</phone>
    <phone_ext>33120</phone_ext>
    <email>dielle.miranda@camh.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Maryland Psychiatric Research Centre</name>
      <address>
        <city>Catonsville</city>
        <state>Maryland</state>
        <zip>21228</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Jennifer Zaranski, MA</last_name>
      <phone>410-402-6060</phone>
      <email>jzaranski@som.umaryland.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>The Feinstein Institute for Medical Research</name>
      <address>
        <city>Manhasset</city>
        <state>New York</state>
        <zip>11030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Andrea Joanlanne, MA</last_name>
      <phone>718-470-8898</phone>
      <email>ajoanlanne@northwell.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Centre for Addiction and Mental Health</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Dielle Miranda, MA</last_name>
      <phone>416-535-8501</phone>
      <phone_ext>33120</phone_ext>
      <email>dielle.miranda@camh.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>May 5, 2020</study_first_submitted>
  <study_first_submitted_qc>June 1, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 5, 2020</study_first_posted>
  <last_update_submitted>April 16, 2021</last_update_submitted>
  <last_update_submitted_qc>April 16, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2021</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>Schizophrenia</mesh_term>
    <mesh_term>Psychotic Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</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/NCT04418011
org study id: 133/2019
nct id: NCT04418011
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: Yes
In this study, the investigators will be examining the effects of repetitive transcranial
      magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS) on social
      cognitive impairments in individuals with schizophrenia spectrum disorders. Participants will
      be chosen by chance to receive either active rTMS stimulation, active iTBS stimulation, sham
      rTMS, or sham iTBS. The investigators predict that active 10Hz and iTBS stimulation will
      improve social cognitive impairments compared to sham stimulation. We aim to identify which
      type of active stimulation is most effective at inducing changes social cognition brain
      circuitry and secondarily which type of active stimulation is best tolerated and most
      effective at inducing changes in social cognitive performance.
This study is a randomized, double blind, sham controlled study which aims to use repetitive
      transcranial magnetic stimulation (rTMS), a form of neuromodulation, to target the neural
      circuitry of social cognitive (SCog) impairments in people with Schizophrenia Spectrum
      Disorders. We will randomize 60 people with SSDs to three groups: 20 to a conventional form
      of rTMS (i.e. 10 Hz rTMS); 20 to intermittent theta burst stimulation (iTBS); and 20 to
      either sham 10Hz rTMS stimulation or sham iTBS. We will determine whether these treatments
      can change the functional connectivity of key SCog brain circuits by targeting a brain region
      known as the dorsomedial prefrontal cortex (DMPFC). Since each person's anatomical and
      functional brain profile is slightly different, we will optimize the orientation and location
      of coil placement in each individual. Overall, our proposal follows a target engagement
      framework, including specifics regarding testing brain stimulation parameters (i.e., rTMS vs.
      iTBS) and individualizing coil placement for optimal targeting. We anticipate that active 10
      Hz rTMS or iTBS will demonstrate target engagement compared to sham, and potentially
      ameliorate SCog deficits in people with SSDs. Our primary goal is to identify which treatment
      best induces change in SCog brain circuitry and secondarily which treatment is best tolerated
      and induces changes in social cognitive performance.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Change in mentalizing brain network functional connectivity
time frame: 2 weeks
description: Measured using the empathic accuracy fMRI task
measure: Treatment Tolerability
time frame: 2 weeks
description: Measured using the Visual Analogue Scale for Pain (VAS)
measure: Treatment Tolerability
time frame: 2 weeks
description: Measured using proportion of participants that report headache
measure: Treatment Tolerability
time frame: 2 weeks
description: Measured using proportion of participants that report dizziness
measure: Treatment Tolerability
time frame: 2 weeks
description: Measured using proportion of treatment related SAE's
arm group label: Active 10 Hz rTMS
arm group type: Active Comparator
description: Active treatment will be targeted to an intensity that is 120% of the resting motor threshold. Stimulation will be delivered at 10 Hz according to conventional FDA-approved parameters (4 s on and 26 s off; 3000 pulses per session; total duration 37.5 mins) .
arm group label: Active iTBS
arm group type: Active Comparator
description: Active iTBS will be targeted to an intensity that is 120% of the resting motor threshold. Stimulation will be delivered in triplet 50 Hz bursts, repeated at 5 Hz; 2 seconds on and 8 seconds off; 600 pulses per session; total duration of 3 min 9 seconds.
arm group label: Sham rTMS
arm group type: Sham Comparator
description: Sham stimulation will be delivered using the same stimulation parameters as either 10 Hz rTMS or iTBS.
For both active and sham stimulation, TMS coil positioning for each individual will be optimized by combining participant fMRI data, meta-analytic functional analysis, electric field modelling, and real-time neuronavigation.
intervention type: Device
intervention name: Repetitive Transcranial Magnetic Stimulation
description: The present study aims to use both repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS), safe and effective forms of neuromodulation, to target the neural circuitry of social cognitive (SCog) impairments in people with SSDs. Treatment sessions will be administered five days per week for two weeks.
Other Name: MagPro X100 or R30 (Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany)
arm group label: Active 10 Hz rTMS
intervention type: Device
intervention name: Repetitive Transcranial Magnetic Stimulation (Intermittent Theta Burst Stimulation)
description: The present study aims to use both repetitive transcranial magnetic stimulation (rTMS) and intermittent theta burst stimulation (iTBS), safe and effective forms of neuromodulation, to target the neural circuitry of social cognitive (SCog) impairments in people with SSDs. Treatment sessions will be administered five days per week for two weeks.
Other Name: MagPro X100 or R30 (Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany)
arm group label: Active iTBS
intervention type: Device
intervention name: Repetitive Transcranial Magnetic Stimulation (Sham)
description: Other Name: MagPro X100 or R30(Medtronic A/S. Copenhagen, Denmark) equipped with a Cool-B70 A/P coil and Qooler fluid-cooling device (MagVenture, Farum, Denmark), positioned under MRI guidance using the Brainsight neuronavigation system (Rogue Resolutions, Montreal, Canada) or Localite (Localite GmbH, Bonn, Germany)
arm group label: Sham rTMS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Aristotle Voineskos, MD
role: Principal Investigator
affiliation: Centre for Addiction and Mental Health
last name: Anil Malhotra, MD
role: Principal Investigator
affiliation: The Feinstein Institute for Medical Research, Zucker Hillside Hospital
last name: Robert Buchanan, MD
role: Principal Investigator
affiliation: Maryland Psychiatric Research Centre, University of Maryland
last name: Aristotle Voineskos, MD
phone: 416-535-8501
phone ext: 34378
email: aristotle.voineskos@camh.ca
last name: Dielle Miranda, MA
phone: 416-535-8501
phone ext: 33120
email: dielle.miranda@camh.ca
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Schizophrenia
mesh term: Psychotic Disorders
sharing ipd: Yes