<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/NCT03026036</url>
  </required_header>
  <id_info>
    <org_study_id>2015P002520</org_study_id>
    <nct_id>NCT03026036</nct_id>
  </id_info>
  <brief_title>Neuroimaging Studies of Reward Processing in Depression</brief_title>
  <official_title>Neuroimaging Studies of Reward Processing in Depression</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mclean Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Mclean Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study investigates stress-related signaling of glutamate and dopamine within the&#xD;
      reward-processing circuit in Major Depressive Disorder (MDD), and whether they can be used to&#xD;
      predict depressive symptoms in the future. This will be achieved through various neuroimaging&#xD;
      tools (MRS, fMRI, PET), behavioral tasks, and a naturalistic follow-up design.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The overarching goals of this research are to investigate: (1) stress-induced glutamatergic&#xD;
      abnormalities and their relation to disruption within the corticostriatal valuation circuit&#xD;
      in MDD; (2) stress-induced DA signaling disruptions in MDD; and (3) the predictive validity&#xD;
      of these two pathophysiological mechanisms. This will be achieved through an innovative&#xD;
      integration of (1) proton magnetic resonance spectroscopy (MRS)-based assessments of&#xD;
      glutamatergic metabolites in the mPFC; (2) functional magnetic resonance imaging (fMRI)&#xD;
      probes of the corticostriatal valuation circuit with well-established stress manipulations&#xD;
      (MAST) and assessments (cortisol and inflammatory markers); (3) positron emission tomography&#xD;
      (PET)-based measurement of striatal DA release with well-established stress manipulations and&#xD;
      assessments (cortisol and inflammatory markers); and (4) a naturalistic follow-up design.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 2016</start_date>
  <completion_date type="Actual">March 2021</completion_date>
  <primary_completion_date type="Actual">March 2021</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>Behavioral Performance on the Probabilistic Stimulus Selection Task</measure>
    <time_frame>Screening visit (Day 0)</time_frame>
    <description>The Probablilistic Reward Task operationalizes positive reinforcement learning</description>
  </primary_outcome>
  <primary_outcome>
    <measure>MRI Data</measure>
    <time_frame>MRI scans for a total of 90 minutes take place within 30 days of Screening Visit</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>PET scan with raclopride</measure>
    <time_frame>a total of 90 minutes take place after the MRI data collection</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Salivary Cortisol</measure>
    <time_frame>6 times during MRI visit (on or before Day 30), and 4 times during PET visit (on or before Day 30)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Four Blood Samples (6ml)</measure>
    <time_frame>During the MRI visit (on or before Day 30)</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Follow-up Clinical Interviews</measure>
    <time_frame>6 months and 12 months after the MRI scanning visit</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Behavioral Performance on the Instrumental Learning Task</measure>
    <time_frame>Administered during MRI scan (on or before Day 30)</time_frame>
    <description>The instrumental learning task is designed to measure participant learning from reward and punishment.</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">123</enrollment>
  <condition>Major Depressive Disorder</condition>
  <arm_group>
    <arm_group_label>MDD</arm_group_label>
    <description>Patients with current Major Depressive Disorder</description>
  </arm_group>
  <arm_group>
    <arm_group_label>rMDD</arm_group_label>
    <description>Patients with a history of Major Depressive Disorder</description>
  </arm_group>
  <arm_group>
    <arm_group_label>HC</arm_group_label>
    <description>Healthy control participants</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>PET Scan with Raclopride</intervention_name>
    <description>A subsample (21 per group) will complete the PET imaging.</description>
    <arm_group_label>HC</arm_group_label>
    <arm_group_label>MDD</arm_group_label>
    <arm_group_label>rMDD</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood samples, saliva samples&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Current Major Depressive Disorder (MDD), or Remitted Major Depressive Disorder (rMDD)&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        General Inclusion Criteria:&#xD;
&#xD;
          -  All genders, races, and ethnic origins, aged between 18 and 45&#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;
        Inclusion Criteria for Current Depression Group (MDD):&#xD;
&#xD;
          -  Current DSM-5 diagnostic criteria for MDD (as diagnosed with the use of the SCID)&#xD;
&#xD;
        Inclusion Criteria for Remitted Depression Group (rMDD):&#xD;
&#xD;
          -  History of at least one major depressive episode within the past five years&#xD;
&#xD;
          -  Not currently depressed&#xD;
&#xD;
        Inclusion Criteria for Healthy Control Group (HC):&#xD;
&#xD;
          -  Absence of any medical, neurological, and psychiatric illness (including&#xD;
             alcohol/substance abuse)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with suicidal ideation where outpatient treatment is determined unsafe by the&#xD;
             study clinician&#xD;
&#xD;
          -  Pregnant women&#xD;
&#xD;
          -  Failure to meet standard MRI or PET safety requirements&#xD;
&#xD;
          -  Serious or unstable medical illness&#xD;
&#xD;
          -  History of seizure disorder&#xD;
&#xD;
          -  History or current diagnosis of organic mental disorder, schizophrenia,&#xD;
             schizoaffective disorder, delusional disorder, psychotic disorders not otherwise&#xD;
             specified, bipolar disorder, OCD, PTSD, mood congruent or mood incongruent psychotic&#xD;
             features, substance dependence, substance abuse within the last 12 months (with the&#xD;
             exception of cocaine or stimulant abuse, which will lead to automatic exclusion)&#xD;
&#xD;
          -  Simple phobia, social anxiety disorder, and generalized anxiety disorder will be&#xD;
             allowed only if secondary to MDD and only in the MDD group&#xD;
&#xD;
          -  History of cocaine or stimulant use (e.g., amphetamine, cocaine, methamphetamine)&#xD;
&#xD;
          -  History of use of dopaminergic drugs (including methylphenidate)&#xD;
&#xD;
          -  Patients with a lifetime history of electroconvulsive therapy (ECT)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 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>David Crowley</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>February 2023</verification_date>
  <study_first_submitted>December 27, 2016</study_first_submitted>
  <study_first_submitted_qc>January 17, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 20, 2017</study_first_posted>
  <last_update_submitted>February 1, 2023</last_update_submitted>
  <last_update_submitted_qc>February 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 3, 2023</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>Depression</keyword>
  <keyword>MRI</keyword>
  <keyword>PET</keyword>
  <keyword>Reward</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Depression</mesh_term>
    <mesh_term>Depressive Disorder</mesh_term>
    <mesh_term>Depressive Disorder, Major</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Raclopride</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All collected IPD will be shared via NIMH Data Archive (as part of data submission agreement)</ipd_description>
    <ipd_time_frame>All collected IPD are shared every 6 months (1/15 and 7/15 of each year)</ipd_time_frame>
    <ipd_access_criteria>Investigators may request for access for approval by the NIMH.</ipd_access_criteria>
  </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/NCT03026036
org study id: 2015P002520
nct id: NCT03026036
lead sponsor: 
has dmc: No
This study investigates stress-related signaling of glutamate and dopamine within the
      reward-processing circuit in Major Depressive Disorder (MDD), and whether they can be used to
      predict depressive symptoms in the future. This will be achieved through various neuroimaging
      tools (MRS, fMRI, PET), behavioral tasks, and a naturalistic follow-up design.
The overarching goals of this research are to investigate: (1) stress-induced glutamatergic
      abnormalities and their relation to disruption within the corticostriatal valuation circuit
      in MDD; (2) stress-induced DA signaling disruptions in MDD; and (3) the predictive validity
      of these two pathophysiological mechanisms. This will be achieved through an innovative
      integration of (1) proton magnetic resonance spectroscopy (MRS)-based assessments of
      glutamatergic metabolites in the mPFC; (2) functional magnetic resonance imaging (fMRI)
      probes of the corticostriatal valuation circuit with well-established stress manipulations
      (MAST) and assessments (cortisol and inflammatory markers); (3) positron emission tomography
      (PET)-based measurement of striatal DA release with well-established stress manipulations and
      assessments (cortisol and inflammatory markers); and (4) a naturalistic follow-up design.
observational model: Case-Control
time perspective: Cross-Sectional
measure: Behavioral Performance on the Probabilistic Stimulus Selection Task
time frame: Screening visit (Day 0)
description: The Probablilistic Reward Task operationalizes positive reinforcement learning
measure: MRI Data
time frame: MRI scans for a total of 90 minutes take place within 30 days of Screening Visit
measure: PET scan with raclopride
time frame: a total of 90 minutes take place after the MRI data collection
measure: Salivary Cortisol
time frame: 6 times during MRI visit (on or before Day 30), and 4 times during PET visit (on or before Day 30)
measure: Four Blood Samples (6ml)
time frame: During the MRI visit (on or before Day 30)
measure: Follow-up Clinical Interviews
time frame: 6 months and 12 months after the MRI scanning visit
measure: Behavioral Performance on the Instrumental Learning Task
time frame: Administered during MRI scan (on or before Day 30)
description: The instrumental learning task is designed to measure participant learning from reward and punishment.
arm group label: MDD
description: Patients with current Major Depressive Disorder
arm group label: rMDD
description: Patients with a history of Major Depressive Disorder
arm group label: HC
description: Healthy control participants
intervention type: Radiation
intervention name: PET Scan with Raclopride
description: A subsample (21 per group) will complete the PET imaging.
arm group label: HC
arm group label: MDD
arm group label: rMDD
blood samples, saliva samples
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 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: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major
mesh term: Raclopride
sharing ipd: Yes
ipd description: All collected IPD will be shared via NIMH Data Archive (as part of data submission agreement)
ipd time frame: All collected IPD are shared every 6 months (1/15 and 7/15 of each year)
ipd access criteria: Investigators may request for access for approval by the NIMH.