<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/NCT03276793</url>
  </required_header>
  <id_info>
    <org_study_id>2021P000335</org_study_id>
    <secondary_id>R01MH113929</secondary_id>
    <nct_id>NCT03276793</nct_id>
  </id_info>
  <brief_title>Brain Connectivity in Depression</brief_title>
  <official_title>Using Human Brain Connectivity to Identify the Causal Neuroanatomical Substrate of Depression Symptoms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Butler Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Brigham and Women's Hospital</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 study originally included 100 subjects with medication-refractory depression undergoing&#xD;
      10 Hz transcranial magnetic stimulation (10Hz-TMS) to the left dorsal lateral prefrontal&#xD;
      cortex (DLPFC), with the goal of having 60 completers with good quality data. Subjects were&#xD;
      recruited from the TMS clinics at Beth Israel Deaconess Medical Center, Brigham &amp; Women's&#xD;
      Hospital, and Butler Hospital. Subjects underwent an hour-long MRI scanning session, an&#xD;
      optional DNA-sample collection, up to three 20 minute neuronavigation sessions for marking&#xD;
      the site of TMS stimulation, questionnaires, and a behavioral testing battery before and&#xD;
      after their TMS treatment course. The task battery included the Emotion Conflict Resolution&#xD;
      (ECR) task, Multi-Source Interference Task (MSIT), War Game (Gambling) task, and Associative&#xD;
      Learning with Reversal task. Subjects' scores on the Quick Inventory of Depressive&#xD;
      Symptomatology (QIDS) and Beck Depression Inventory (BDI) were assessed before and after the&#xD;
      TMS course. MRI data was utilized to identify brain regions whose connectivity to the&#xD;
      stimulation site co-varies with the aforementioned measures of symptom improvement. This was&#xD;
      the only study group until August 30, 2022, and the primary outcome was analyzed for the&#xD;
      10Hz-TMS group.&#xD;
&#xD;
      Due to changes in clinical standard of care from 10Hz-TMS to a newer version of TMS termed&#xD;
      intermittent theta burst (iTBS), in September 2022 a second group was added to include&#xD;
      patients receiving this new form of TMS. This second group included another 100 patients with&#xD;
      medication-refractory depression undergoing iTBS to the left dorsal lateral prefrontal cortex&#xD;
      (DLPFC), with the intent to have 80 completers. Massachusetts General Hospital was added as a&#xD;
      data collection site in lieu of Butler Hospital. Subjects will undergo an hour-long MRI&#xD;
      scanning session, up to three 20 minute neuronavigation sessions for marking the site of TMS&#xD;
      stimulation, questionnaires, and a behavioral testing battery before and after their TMS&#xD;
      treatment course. The task battery will included the Emotion Conflict Resolution (ECR) task,&#xD;
      Multi-Source Interference Task (MSIT), Penn Emotion Recognition Test, the Suicide/Death&#xD;
      Implicit Association Test, and Associative Learning with Reversal task. Subjects' scores on&#xD;
      the Beck Depression Inventory (BDI) were assessed before and after the TMS course. MRI data&#xD;
      will be utilized to identify brain regions whose connectivity to the stimulation site&#xD;
      co-varies with the aforementioned measures of symptom improvement.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study was originally approved by the Beth Israel Deaconess Medical Center (BIDMC)&#xD;
      Institutional Review Board (IRB) with Butler Hospital as a relying site. The study was&#xD;
      transferred to the Mass General Brigham (MGB) IRB in 2020 when Dr. Fox (lead PI) moved to&#xD;
      Brigham and Women's Hospital (BWH). Butler Hospital continued to enroll subjects, relying on&#xD;
      the MGB IRB for regulatory oversight, while BIDMC stopped enrolling subjects. A Data Usage&#xD;
      Agreement was established between BIDMC and BWH, and all previously collected Data was&#xD;
      de-identified and sent to BWH. The protocol at BIDMC will remain active but not enrolling&#xD;
      until all the de-identified data has been sent to BWH.&#xD;
&#xD;
      In Sept 2022, with the launch of the second iTBS group, Massachusetts General Hospital&#xD;
      replaced Butler Hospital as the secondary enrollment site, while enrollment continued at&#xD;
      Brigham and Women's Hospital.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">April 3, 2018</start_date>
  <completion_date type="Anticipated">October 31, 2027</completion_date>
  <primary_completion_date type="Anticipated">September 30, 2027</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Prediction of repetitive Transcranial Magnetic Stimulation (rTMS) clinical response</measure>
    <time_frame>1 year after study completion</time_frame>
    <description>Connectivity between each patient's stimulation site and the subgenual cingulate will be used to predict clinical response to rTMS in the first group (data collected starting in 2017).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Prediction of intermittent theta burst stimulation (iTBS) clinical response</measure>
    <time_frame>1 year after study completion</time_frame>
    <description>Normative connectivity of each patient's stimulation site to a previously-published &quot;depression network&quot; (Siddiqi et al., Nat Hum Behav 2021) will be used to predict clinical response to iTBS in the second group added in September 2022.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">200</enrollment>
  <condition>Depression</condition>
  <arm_group>
    <arm_group_label>MRI and behavioral assessment for patients receiving TMS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects will undergo an hour-long MRI scanning session, a marking for the site of planned clinical TMS stimulation and a behavioral testing battery before and after their TMS treatment course.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>MRI scan</intervention_name>
    <description>Patients will undergo an MRI scan</description>
    <arm_group_label>MRI and behavioral assessment for patients receiving TMS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Behavioral testing</intervention_name>
    <description>Patients will complete a series of cognitive tasks</description>
    <arm_group_label>MRI and behavioral assessment for patients receiving TMS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Male or female&#xD;
&#xD;
          2. Aged 18-70.&#xD;
&#xD;
          3. Have previously received or will receive TMS to the left dorsal-lateral prefrontal&#xD;
             cortex as part of the clinical treatment program at the Center for Brain Circuit&#xD;
             Therapeutics at Brigham and Women's Hospital, or at Massachusetts General Hospital for&#xD;
             treatment of medication resistant depression&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History of bipolar disorder (lifetime), schizophrenia or psychosis (lifetime),&#xD;
             obsessive-compulsive disorder (unstable in past six months), posttraumatic stress&#xD;
             disorder (unstable in past six months), eating disorders (unstable in past six&#xD;
             months), or moderate to severe substance use disorders (currently active, with the&#xD;
             exception of nicotine and cannabis)&#xD;
&#xD;
          2. Presence of a significant neurologic disorder (i.e. Parkinson's Disease, stroke,&#xD;
             Alzheimer's Disease, tumor, multiple sclerosis, epilepsy). Of note, many of these are&#xD;
             also contraindications to receiving TMS and these patients would not be enrolled in&#xD;
             the clinical treatment program.&#xD;
&#xD;
          3. Patients who are pregnant or lactating (by menstrual history)&#xD;
&#xD;
          4. Current abuse of an illicit substance (e.g. marijuana, cocaine, heroin, hallucinogens,&#xD;
             psychostimulants)&#xD;
&#xD;
          5. Positive MRI screen that would preclude the subject from undergoing magnetic resonance&#xD;
             imaging. These include, but are not limited to any of the following:&#xD;
&#xD;
               1. Known metal in the head (such as a surgical aneurysm clip), or a history of prior&#xD;
                  neurosurgical procedures&#xD;
&#xD;
               2. Ferromagnetic bioimplants activated by any electronic, mechanical or magnetic&#xD;
                  means such as: cochlear implants, pacemakers, medication pumps, vagal&#xD;
                  stimulators, deep brain stimulators, neurostimulators, biostimulators, or&#xD;
                  ventriculo-peritoneal shunts&#xD;
&#xD;
               3. Subjects who have or might have bullet fragments or other metal fragments&#xD;
                  (veterans or workers exposed to metal in their work environment)&#xD;
&#xD;
               4. Subjects with metallic paint (e.g. color contact lenses, tattoos, metallic&#xD;
                  eyeliner)&#xD;
&#xD;
               5. Subjects expressing significant anxiety or claustrophobia about being in the&#xD;
                  magnet.&#xD;
&#xD;
          6. Subjects that cannot adhere to the experimental protocol for any reason.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Stephan Palm, BS</last_name>
    <phone>617-732-6658</phone>
    <email>bwhtmstrials@bwh.harvard.edu</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Maya Pattin, BS</last_name>
    <email>bwhtmstrials@bwh.harvard.edu</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Michael D Fox, MD, PhD</last_name>
      <phone>617-732-7432</phone>
      <email>mdfox@bwh.harvard.edu</email>
    </contact>
    <investigator>
      <last_name>Michael D Fox, MD, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Joseph J Taylor, MD, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Shan H Siddiqi, MD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Stephan T Palm, BS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Christopher Lin, BS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Dania Haj-Darwish, BS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Summer B Frandsen, BS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>William Drew, BS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Sanaz Khosravani, PhD</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02129</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Tracy A Barbour, MD</last_name>
      <phone>617-726-5340</phone>
      <email>TBARBOUR@PARTNERS.ORG</email>
    </contact>
    <contact_backup>
      <last_name>Stephanie R Kramer, BS</last_name>
      <email>SKRAMER5@mgh.harvard.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Tracy A Barbour, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Joan A Camprodon, MD, MPH, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
    <investigator>
      <last_name>Nicole L Brocious, BS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Christopher J Funes, MS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>James R Coleman, BS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Anna Moser, MS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Olivia J Newman, BS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Astrid Warney, MS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
    <investigator>
      <last_name>Stephanie R Kramer, BS</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Beth Israel Deaconess Medical Center</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02215</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Completed</status>
  </location>
  <location>
    <facility>
      <name>Butler Hospital</name>
      <address>
        <city>Providence</city>
        <state>Rhode Island</state>
        <zip>02906</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Active, not recruiting</status>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 7, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 8, 2017</study_first_posted>
  <last_update_submitted>August 7, 2023</last_update_submitted>
  <last_update_submitted_qc>August 7, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Brigham and Women's Hospital</investigator_affiliation>
    <investigator_full_name>Michael D. Fox, M.D.,Ph.D.</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT03276793
org study id: 2021P000335
secondary id: R01MH113929
nct id: NCT03276793
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study originally included 100 subjects with medication-refractory depression undergoing
      10 Hz transcranial magnetic stimulation (10Hz-TMS) to the left dorsal lateral prefrontal
      cortex (DLPFC), with the goal of having 60 completers with good quality data. Subjects were
      recruited from the TMS clinics at Beth Israel Deaconess Medical Center, Brigham & Women's
      Hospital, and Butler Hospital. Subjects underwent an hour-long MRI scanning session, an
      optional DNA-sample collection, up to three 20 minute neuronavigation sessions for marking
      the site of TMS stimulation, questionnaires, and a behavioral testing battery before and
      after their TMS treatment course. The task battery included the Emotion Conflict Resolution
      (ECR) task, Multi-Source Interference Task (MSIT), War Game (Gambling) task, and Associative
      Learning with Reversal task. Subjects' scores on the Quick Inventory of Depressive
      Symptomatology (QIDS) and Beck Depression Inventory (BDI) were assessed before and after the
      TMS course. MRI data was utilized to identify brain regions whose connectivity to the
      stimulation site co-varies with the aforementioned measures of symptom improvement. This was
      the only study group until August 30, 2022, and the primary outcome was analyzed for the
      10Hz-TMS group.

      Due to changes in clinical standard of care from 10Hz-TMS to a newer version of TMS termed
      intermittent theta burst (iTBS), in September 2022 a second group was added to include
      patients receiving this new form of TMS. This second group included another 100 patients with
      medication-refractory depression undergoing iTBS to the left dorsal lateral prefrontal cortex
      (DLPFC), with the intent to have 80 completers. Massachusetts General Hospital was added as a
      data collection site in lieu of Butler Hospital. Subjects will undergo an hour-long MRI
      scanning session, up to three 20 minute neuronavigation sessions for marking the site of TMS
      stimulation, questionnaires, and a behavioral testing battery before and after their TMS
      treatment course. The task battery will included the Emotion Conflict Resolution (ECR) task,
      Multi-Source Interference Task (MSIT), Penn Emotion Recognition Test, the Suicide/Death
      Implicit Association Test, and Associative Learning with Reversal task. Subjects' scores on
      the Beck Depression Inventory (BDI) were assessed before and after the TMS course. MRI data
      will be utilized to identify brain regions whose connectivity to the stimulation site
      co-varies with the aforementioned measures of symptom improvement.
This study was originally approved by the Beth Israel Deaconess Medical Center (BIDMC)
      Institutional Review Board (IRB) with Butler Hospital as a relying site. The study was
      transferred to the Mass General Brigham (MGB) IRB in 2020 when Dr. Fox (lead PI) moved to
      Brigham and Women's Hospital (BWH). Butler Hospital continued to enroll subjects, relying on
      the MGB IRB for regulatory oversight, while BIDMC stopped enrolling subjects. A Data Usage
      Agreement was established between BIDMC and BWH, and all previously collected Data was
      de-identified and sent to BWH. The protocol at BIDMC will remain active but not enrolling
      until all the de-identified data has been sent to BWH.

      In Sept 2022, with the launch of the second iTBS group, Massachusetts General Hospital
      replaced Butler Hospital as the secondary enrollment site, while enrollment continued at
      Brigham and Women's Hospital.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Prediction of repetitive Transcranial Magnetic Stimulation (rTMS) clinical response
time frame: 1 year after study completion
description: Connectivity between each patient's stimulation site and the subgenual cingulate will be used to predict clinical response to rTMS in the first group (data collected starting in 2017).
measure: Prediction of intermittent theta burst stimulation (iTBS) clinical response
time frame: 1 year after study completion
description: Normative connectivity of each patient's stimulation site to a previously-published "depression network" (Siddiqi et al., Nat Hum Behav 2021) will be used to predict clinical response to iTBS in the second group added in September 2022.
arm group label: MRI and behavioral assessment for patients receiving TMS
arm group type: Experimental
description: Subjects will undergo an hour-long MRI scanning session, a marking for the site of planned clinical TMS stimulation and a behavioral testing battery before and after their TMS treatment course.
intervention type: Other
intervention name: MRI scan
description: Patients will undergo an MRI scan
arm group label: MRI and behavioral assessment for patients receiving TMS
intervention type: Behavioral
intervention name: Behavioral testing
description: Patients will complete a series of cognitive tasks
arm group label: MRI and behavioral assessment for patients receiving TMS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Stephan Palm, BS
phone: 617-732-6658
email: bwhtmstrials@bwh.harvard.edu
last name: Maya Pattin, BS
email: bwhtmstrials@bwh.harvard.edu
facility: 
status: Recruiting
contact: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
investigator: 
facility: 
status: Completed
facility: 
status: Active, not recruiting
country: United States
responsible party type: Principal Investigator
investigator affiliation: Brigham and Women's Hospital
investigator full name: Michael D. Fox, M.D.,Ph.D.
investigator title: Associate Professor
mesh term: Depression
mesh term: Depressive Disorder
sharing ipd: Undecided