<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/NCT03031665</url>
  </required_header>
  <id_info>
    <org_study_id>2016P000693</org_study_id>
    <nct_id>NCT03031665</nct_id>
  </id_info>
  <brief_title>Sex, Hormones and Gamma-Aminobutyric Acid (GABA) in Stress Induced Anhedonia in Depression</brief_title>
  <official_title>Sex, Hormones and GABA in Stress Induced Anhedonia in Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mclean Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Brigham and Women's Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Mclean Hospital</source>
  <oversight_info>
    <has_dmc>No</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>
      Using an innovative multi-modal imaging approach, this study investigates the role of the&#xD;
      neurochemical gamma-aminobutyric acid (GABA), brain activity, as well as hormones in&#xD;
      understanding sex differences in Major Depressive Disorder (MDD). Further, the investigators&#xD;
      will link these markers to symptoms of depression.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The goals of this research are to investigate: (1) functional and neurochemical features&#xD;
      associated with depression irrespective of clinical state; (2) moderating effects of hormones&#xD;
      on stress circuitry in MDD; and (3) sex differences in symptoms. To this end, the study is&#xD;
      enrolling adults with current depression and remitted depression, along with a control group&#xD;
      of psychiatrically health adults. Participants will have an magnetic resonance imaging (MRI)&#xD;
      exam involving multiple imaging techniques (functional, structural, spectroscopic) while&#xD;
      performing computer-based tests. Additional questionnaires and tests will be done outside the&#xD;
      scanner to assess current symptoms and hormone levels. The integration of laboratory-based&#xD;
      measures of reward and stress sensitivity, with state-of-the-art imaging techniques and&#xD;
      hormonal assessments promises to provide novel insights in the sex-dependent manifestation&#xD;
      and pathophysiology of MDD.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date type="Actual">October 1, 2017</start_date>
  <completion_date type="Anticipated">April 30, 2024</completion_date>
  <primary_completion_date type="Actual">April 30, 2022</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Cross-Sectional</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Blood oxygen level-dependent (BOLD) activation in response to stress</measure>
    <time_frame>Baseline.</time_frame>
    <description>Region-specific BOLD activation in response to stress in hypothalamus, amygdala, medial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, and hippocampus</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Network-specific effective connectivity</measure>
    <time_frame>Baseline</time_frame>
    <description>Region-specific resting state connectivity of two networks (1) hypothalamus and amygdala, with medial prefrontal cortex and orbitofrontal cortex; and (2) hypothalamus and amygdala, with hippocampus</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>GABA concentration</measure>
    <time_frame>Baseline</time_frame>
    <description>Region-specific GABA concentration measured in rostral anterior cingulate cortex and dorsolateral prefrontal cortex</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">251</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>Current MDD</arm_group_label>
    <description>Subjects experiencing a current episode of Major Depressive Disorder.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Remitted MDD</arm_group_label>
    <description>Subjects who have a history of Major Depressive Disorder, but have not had a depressive episode for at least two months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Subjects</arm_group_label>
    <description>Subjects who have no history of clinical depression or other psychological disorder.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Young adults (ages 18 to 25).&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria for all participants.&#xD;
&#xD;
          -  Males and females aged 18 through 25&#xD;
&#xD;
          -  Capable of providing written informed consent, and fluent in English&#xD;
&#xD;
          -  Right-handed&#xD;
&#xD;
          -  Absence of any psychotropic medications for at least 2 weeks&#xD;
&#xD;
          -  Female subjects will be scheduled to participate during the follicular phase of their&#xD;
             menstrual cycle&#xD;
&#xD;
        Inclusion Criteria for &quot;Current MDD&quot; group:&#xD;
&#xD;
          -  Meets inclusion criteria for all subjects, plus:&#xD;
&#xD;
          -  Meets diagnostic criteria for a current episode of Major Depressive Disorder (MDD), as&#xD;
             defined by the Diagnostic and Statistical Manual of Mental Disorders (DSM-5).&#xD;
&#xD;
        Inclusion Criteria for &quot;Remitted MDD&quot; group:&#xD;
&#xD;
          -  Meets inclusion criteria for all subjects, plus:&#xD;
&#xD;
          -  History of MDD as defined by DSM-5, but in remission for the past two months&#xD;
&#xD;
          -  Absence of anxiety disorder for the past two months&#xD;
&#xD;
        Exclusion Criteria for all participants:&#xD;
&#xD;
          -  History of psychiatric illnesses, other than depression or anxiety disorders among the&#xD;
             Current MDD and Remitted MDD groups.&#xD;
&#xD;
          -  History of psychotic episodes, suicidal ideation, or of electroconvulsive therapy&#xD;
             (ECT) treatment&#xD;
&#xD;
          -  Use of hormone replacement therapy, or of anabolic steroids.&#xD;
&#xD;
          -  Use of hormonal contraceptives is permitted for female subjects only if the subject&#xD;
             has regular menses&#xD;
&#xD;
          -  Failure to meet any MRI safety requirements&#xD;
&#xD;
          -  Serious or unstable medical illness, or history of neurological disease or damage&#xD;
&#xD;
          -  History of use of cocaine, stimulants, or dopaminergic drugs&#xD;
&#xD;
          -  History of substance use disorder or alcohol use disorder (as these terms are defined&#xD;
             by DSM-5); except depressed subjects may have a history of 'Mild' substance/alcohol&#xD;
             use disorder only if it ended as least 12 months ago.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>25 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Diego A Pizzagalli, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mclean Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>McLean Hospital</name>
      <address>
        <city>Belmont</city>
        <state>Massachusetts</state>
        <zip>02478</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 20, 2017</study_first_submitted>
  <study_first_submitted_qc>January 23, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>October 28, 2022</last_update_submitted>
  <last_update_submitted_qc>October 28, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 1, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mclean Hospital</investigator_affiliation>
    <investigator_full_name>Diego Pizzagalli</investigator_full_name>
    <investigator_title>Professor, Department of Psychiatry, Harvard Medical School</investigator_title>
  </responsible_party>
  <keyword>GABA</keyword>
  <keyword>Depression</keyword>
  <keyword>Stress</keyword>
  <keyword>Androgens</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Anhedonia</mesh_term>
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</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/NCT03031665
org study id: 2016P000693
nct id: NCT03031665
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Using an innovative multi-modal imaging approach, this study investigates the role of the
      neurochemical gamma-aminobutyric acid (GABA), brain activity, as well as hormones in
      understanding sex differences in Major Depressive Disorder (MDD). Further, the investigators
      will link these markers to symptoms of depression.
The goals of this research are to investigate: (1) functional and neurochemical features
      associated with depression irrespective of clinical state; (2) moderating effects of hormones
      on stress circuitry in MDD; and (3) sex differences in symptoms. To this end, the study is
      enrolling adults with current depression and remitted depression, along with a control group
      of psychiatrically health adults. Participants will have an magnetic resonance imaging (MRI)
      exam involving multiple imaging techniques (functional, structural, spectroscopic) while
      performing computer-based tests. Additional questionnaires and tests will be done outside the
      scanner to assess current symptoms and hormone levels. The integration of laboratory-based
      measures of reward and stress sensitivity, with state-of-the-art imaging techniques and
      hormonal assessments promises to provide novel insights in the sex-dependent manifestation
      and pathophysiology of MDD.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Blood oxygen level-dependent (BOLD) activation in response to stress
time frame: Baseline.
description: Region-specific BOLD activation in response to stress in hypothalamus, amygdala, medial prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex, and hippocampus
measure: Network-specific effective connectivity
time frame: Baseline
description: Region-specific resting state connectivity of two networks (1) hypothalamus and amygdala, with medial prefrontal cortex and orbitofrontal cortex; and (2) hypothalamus and amygdala, with hippocampus
measure: GABA concentration
time frame: Baseline
description: Region-specific GABA concentration measured in rostral anterior cingulate cortex and dorsolateral prefrontal cortex
arm group label: Current MDD
description: Subjects experiencing a current episode of Major Depressive Disorder.
arm group label: Remitted MDD
description: Subjects who have a history of Major Depressive Disorder, but have not had a depressive episode for at least two months.
arm group label: Control Subjects
description: Subjects who have no history of clinical depression or other psychological disorder.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 25 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Diego A Pizzagalli, Ph.D.
role: Principal Investigator
affiliation: Mclean Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Mclean Hospital
investigator full name: Diego Pizzagalli
investigator title: Professor, Department of Psychiatry, Harvard Medical School
mesh term: Anhedonia
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
sharing ipd: No