<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/NCT01701141</url>
  </required_header>
  <id_info>
    <org_study_id>2009-P-001360</org_study_id>
    <nct_id>NCT01701141</nct_id>
  </id_info>
  <brief_title>Depression and Dopamine Transporter Function Study Using C-11 Altropane</brief_title>
  <official_title>Depression and Dopamine Transporter Function: A Positron Emission Tomography Study Using C-11 Altropane</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>
      Major depressive disorder (MDD) is often characterized by anhedonia and impaired ability to&#xD;
      modulate behavior as a function of rewards. However, the neurobiology of anhedonia and&#xD;
      reduced reward responsiveness remains largely unknown. Because dopamine (DA) plays a critical&#xD;
      role in goal-directed behavior and reinforcement learning, DA dysregulation might play an&#xD;
      important role. In fact, several lines of evidence suggest that down-regulation of DA&#xD;
      transmission might characterize depression vulnerability and the emergence of depressive&#xD;
      symptoms. The current study seeks to elucidate the role of DA dysfunction in MDD. We&#xD;
      hypothesize that MDD subjects will show reduced DAT binding potential, reduced reward&#xD;
      learning in the probabilistic reward task, and abnormal functional magnetic resonance imaging&#xD;
      (fMRI) activation in dorsal and ventral striatal regions during an instrumental learning&#xD;
      task.&#xD;
&#xD;
      This study will include three sessions.&#xD;
&#xD;
      The first will take place at Massachusetts General Hospital or at McLean Hospital's Center&#xD;
      for Depression, Anxiety and Stress Research. The aims of this session will be to (a) explain&#xD;
      the study; (b) collect written informed consent, and (c) assess the subject's eligibility.&#xD;
&#xD;
      Following this, another session (either second or third in order) will take place at the MGH&#xD;
      PET Imaging Laboratory. Participants will complete a PET scan and a probabilistic reward task&#xD;
      designed to measure reward learning and sensitivity to reward. The radioactive tracer&#xD;
      utilized is 11C-altropane.&#xD;
&#xD;
      Another session (either second or third in order) will take place at the McLean Hospital&#xD;
      Neuroimaging Center. Participants will complete an instrumental learning task while in the&#xD;
      fMRI, followed by a social reinforcement learning task and an implicit learning serial&#xD;
      reaction time task upon completion of the scan. In the instrumental learning task,&#xD;
      participants have the opportunity to earn money but need to learn, by trial and error,&#xD;
      stimulus-outcome associations. The social reinforcement learning task is designed to&#xD;
      investigate whether learning deficits in MDD are specific to learning from monetary&#xD;
      incentives or whether the learning deficits are more global and are affected when learning&#xD;
      from social rewards and punishments. Participants will also complete an implicit learning&#xD;
      serial reaction time task, designed to exclude the possibility of global learning deficits in&#xD;
      MDD.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2012</start_date>
  <completion_date type="Actual">July 2014</completion_date>
  <primary_completion_date type="Actual">July 2014</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>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>11C-Altropane Binding</measure>
    <time_frame>1 hour long PET scan during session 2</time_frame>
    <description>11C-altropane binding is recording during the positron emission tomography (PET) scan and is used to measure dopamine transporter levels.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Behavioral Performance in Probabilistic Reward Task</measure>
    <time_frame>20 minute task administered during session 2</time_frame>
    <description>The probabilistic reward task is designed to measure sensitivity to reward and reward learning.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Brain Activity during Instrumental Learning Task</measure>
    <time_frame>30 minute long fMRI scan during session 3</time_frame>
    <description>Functional magnetic resonance imaging (fMRI) data are acquired while participants perform the instrumental learning task. fMRI data allows us to measure aspects of brain activity.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Behavioral Performance in Instrumental Learning Task</measure>
    <time_frame>30 minute task administered during session 3</time_frame>
    <description>The instrumental learning task is designed to measure participant learning from reward and punishment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Behavioral Performance in the Social Reinforcement Learning Task</measure>
    <time_frame>15 minute task administered during session 3</time_frame>
    <description>The social reinforcement learning task is designed to investigate whether learning deficits in MDD are specific to learning from monetary incentives or whether the learning deficits are more global and are affected when learning from social rewards and punishments.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Questionnaire Data</measure>
    <time_frame>Self-report measures are administered at all 3 sessions which take place within an average of 2-3 weeks</time_frame>
    <description>At all sessions participants will fill out self-report questionnaires regarding aspects of mood and affect, demographics, caffeine and alcohol consumption, etc.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Behavioral Performance in Implicit Learning Serial Reaction Time Task</measure>
    <time_frame>5 minute task administered during session 3</time_frame>
    <description>The implicit learning serial reaction time task is designed to exclude the possibility of global learning deficits in major depressive disorder.</description>
  </secondary_outcome>
  <number_of_groups>2</number_of_groups>
  <enrollment type="Anticipated">150</enrollment>
  <condition>Major Depressive Disorder</condition>
  <condition>Anhedonia</condition>
  <arm_group>
    <arm_group_label>Individuals with MDD</arm_group_label>
    <description>Individuals with current MDD as determined by structured clinical interview for DSM-IV (SCID) at time of enrollment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy Controls</arm_group_label>
    <description>Individuals with no psychiatric diagnosis as determined by structured clinical interview for DSM-IV (SCID) at time of enrollment</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Community Sample&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Criteria for All Subjects&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Written informed consent;&#xD;
&#xD;
          2. Both genders and all ethnic origins, age between 18 and 45;&#xD;
&#xD;
          3. Right-handed (Chapman and Chapman 1987);&#xD;
&#xD;
          4. Absence of any medications for at least 3 weeks;&#xD;
&#xD;
          5. Absence of pregnancy;&#xD;
&#xD;
          6. Absence of current drug use (cocaine, cannabinoids, opiates, amphetamines,&#xD;
             benzodiazepines and barbiturates) as assessed by urinary drug test.&#xD;
&#xD;
          7. For women, completion of a negative urine pregnancy test prior to the MRI scan, as&#xD;
             well as a negative STAT quantitative serum hCG test immediately prior to&#xD;
             radiopharmaceutical exposure;&#xD;
&#xD;
          8. Normal or corrected-to-normal vision and hearing.&#xD;
&#xD;
        Exclusion Criteria&#xD;
&#xD;
          1. Pregnant or currently breast-feeding women or any woman of childbearing potential who&#xD;
             is seeking to become pregnant or suspects that she may be pregnant.&#xD;
&#xD;
          2. History or current serious or unstable medical illness, including cancer,&#xD;
             cardiovascular, hepatic, renal, respiratory, endocrine, neurologic or hematologic&#xD;
             disease;&#xD;
&#xD;
          3. History of seizure disorder;&#xD;
&#xD;
          4. Failure to meet standard PET safety requirements;&#xD;
&#xD;
          5. Failure to meet standard fMRI safety requirements;&#xD;
&#xD;
          6. Students and employees supervised by the Investigators at MGH, McLean Hospital and&#xD;
             Harvard University;&#xD;
&#xD;
          7. Absence of fluency in written and spoken English;&#xD;
&#xD;
          8. History of head injury;&#xD;
&#xD;
          9. History or current use of cocaine, stimulants, or other dopaminergic drugs.&#xD;
&#xD;
         10. Diabetes with poor glucose control;&#xD;
&#xD;
         11. History or current diagnosis of dementia, or a score of &lt; 26 on the Mini Mental Status&#xD;
             Examination (Folstein, 1975) at the screening visit;&#xD;
&#xD;
         12. Clinical or laboratory evidence of hypothyroidism or currently taking thyroid&#xD;
             medication;&#xD;
&#xD;
         13. Currently taking medication that affects blood flow, e.g. certain blood pressure&#xD;
             medications&#xD;
&#xD;
         14. Evidence of significant inconsistencies in self-report.&#xD;
&#xD;
        Criteria Specific to MDD subjects&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. DSM-IV diagnostic criteria for MDD (diagnosed with the use of the SCID);&#xD;
&#xD;
          2. A baseline HRSD score (Hamilton 1960) greater than or equal to 16 (17-item version);&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Subjects with suicidal ideation where outpatient treatment is determined unsafe by the&#xD;
             study clinician. These patients will be immediately referred to appropriate clinical&#xD;
             treatment;&#xD;
&#xD;
          2. History or current diagnosis of: learning and developmental disorders (including ADHD&#xD;
             and autism spectrum disorders), anorexia nervosa, cognitive disorders, somatoform and&#xD;
             factitious disorders, dissociative disorders, personality disorders, organic mental&#xD;
             disorders, schizophrenia or other psychotic disorder, bipolar disorder, obsessive&#xD;
             compulsive disorder; simple phobia, social anxiety disorder and generalized anxiety&#xD;
             disorder are allowed if secondary to MDD.&#xD;
&#xD;
          3. History of substance dependence lifetime or substance abuse within the last 12 months;&#xD;
&#xD;
          4. History of bulimia nervosa or PTSD within the past 2 years;&#xD;
&#xD;
          5. History or current diagnosis of dementia, or a score of &lt; 26 on the Mini Mental Status&#xD;
             Examination (Folstein, 1975) at the screening visit;&#xD;
&#xD;
          6. Current use of other psychotropic drugs;&#xD;
&#xD;
          7. Patients with lifetime electroconvulsive therapy (ECT);&#xD;
&#xD;
          8. Presence of any psychotropic medications for at least 2 weeks:&#xD;
&#xD;
               -  6 months for dopaminergic drugs (including methylphenidate),&#xD;
&#xD;
               -  6 weeks for fluoxetine,&#xD;
&#xD;
               -  6 months for neuroleptics,&#xD;
&#xD;
               -  2 weeks for benzodiazepines,&#xD;
&#xD;
               -  2 weeks for any other antidepressants.&#xD;
&#xD;
        Criteria Specific to Control subjects&#xD;
&#xD;
        Inclusion Criteria:&#xD;
&#xD;
          1. Absence of medical, neurological, and psychiatric illness (including alcohol and&#xD;
             substance abuse), as assessed by subject history and a structured clinical interview&#xD;
             (SCID-I/NP);&#xD;
&#xD;
          2. Absence of any medications for at least 3 weeks;&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. History or current diagnosis of any of DSM-IV psychiatric illness;&#xD;
&#xD;
          2. First degree relative with mood disorder or psychosis;&#xD;
&#xD;
          3. History or current use of any psychiatric medication.&#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 Pizzagalli, PhD</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>
    <facility>
      <name>Massachusetts General Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02114</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2018</verification_date>
  <study_first_submitted>October 2, 2012</study_first_submitted>
  <study_first_submitted_qc>October 3, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 4, 2012</study_first_posted>
  <last_update_submitted>May 18, 2018</last_update_submitted>
  <last_update_submitted_qc>May 18, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">May 21, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mclean Hospital</investigator_affiliation>
    <investigator_full_name>Diego A. Pizzagalli</investigator_full_name>
    <investigator_title>Associate Professor, Department of Psychiatry, Harvard Medical School</investigator_title>
  </responsible_party>
  <keyword>Positron Emission Tomography (PET)</keyword>
  <keyword>Magnetic resonance imaging (MRI)</keyword>
  <keyword>reward</keyword>
  <keyword>stress</keyword>
  <keyword>learning</keyword>
  <keyword>Major Depressive Disorder</keyword>
  <keyword>Anhedonia</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>
  <!-- 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/NCT01701141
org study id: 2009-P-001360
nct id: NCT01701141
lead sponsor: 
has dmc: No
Major depressive disorder (MDD) is often characterized by anhedonia and impaired ability to
      modulate behavior as a function of rewards. However, the neurobiology of anhedonia and
      reduced reward responsiveness remains largely unknown. Because dopamine (DA) plays a critical
      role in goal-directed behavior and reinforcement learning, DA dysregulation might play an
      important role. In fact, several lines of evidence suggest that down-regulation of DA
      transmission might characterize depression vulnerability and the emergence of depressive
      symptoms. The current study seeks to elucidate the role of DA dysfunction in MDD. We
      hypothesize that MDD subjects will show reduced DAT binding potential, reduced reward
      learning in the probabilistic reward task, and abnormal functional magnetic resonance imaging
      (fMRI) activation in dorsal and ventral striatal regions during an instrumental learning
      task.

      This study will include three sessions.

      The first will take place at Massachusetts General Hospital or at McLean Hospital's Center
      for Depression, Anxiety and Stress Research. The aims of this session will be to (a) explain
      the study; (b) collect written informed consent, and (c) assess the subject's eligibility.

      Following this, another session (either second or third in order) will take place at the MGH
      PET Imaging Laboratory. Participants will complete a PET scan and a probabilistic reward task
      designed to measure reward learning and sensitivity to reward. The radioactive tracer
      utilized is 11C-altropane.

      Another session (either second or third in order) will take place at the McLean Hospital
      Neuroimaging Center. Participants will complete an instrumental learning task while in the
      fMRI, followed by a social reinforcement learning task and an implicit learning serial
      reaction time task upon completion of the scan. In the instrumental learning task,
      participants have the opportunity to earn money but need to learn, by trial and error,
      stimulus-outcome associations. The social reinforcement learning task is designed to
      investigate whether learning deficits in MDD are specific to learning from monetary
      incentives or whether the learning deficits are more global and are affected when learning
      from social rewards and punishments. Participants will also complete an implicit learning
      serial reaction time task, designed to exclude the possibility of global learning deficits in
      MDD.
observational model: Case-Control
time perspective: Prospective
measure: 11C-Altropane Binding
time frame: 1 hour long PET scan during session 2
description: 11C-altropane binding is recording during the positron emission tomography (PET) scan and is used to measure dopamine transporter levels.
measure: Behavioral Performance in Probabilistic Reward Task
time frame: 20 minute task administered during session 2
description: The probabilistic reward task is designed to measure sensitivity to reward and reward learning.
measure: Brain Activity during Instrumental Learning Task
time frame: 30 minute long fMRI scan during session 3
description: Functional magnetic resonance imaging (fMRI) data are acquired while participants perform the instrumental learning task. fMRI data allows us to measure aspects of brain activity.
measure: Behavioral Performance in Instrumental Learning Task
time frame: 30 minute task administered during session 3
description: The instrumental learning task is designed to measure participant learning from reward and punishment.
measure: Behavioral Performance in the Social Reinforcement Learning Task
time frame: 15 minute task administered during session 3
description: The social reinforcement learning task is designed to investigate whether learning deficits in MDD are specific to learning from monetary incentives or whether the learning deficits are more global and are affected when learning from social rewards and punishments.
measure: Questionnaire Data
time frame: Self-report measures are administered at all 3 sessions which take place within an average of 2-3 weeks
description: At all sessions participants will fill out self-report questionnaires regarding aspects of mood and affect, demographics, caffeine and alcohol consumption, etc.
measure: Behavioral Performance in Implicit Learning Serial Reaction Time Task
time frame: 5 minute task administered during session 3
description: The implicit learning serial reaction time task is designed to exclude the possibility of global learning deficits in major depressive disorder.
arm group label: Individuals with MDD
description: Individuals with current MDD as determined by structured clinical interview for DSM-IV (SCID) at time of enrollment.
arm group label: Healthy Controls
description: Individuals with no psychiatric diagnosis as determined by structured clinical interview for DSM-IV (SCID) at time of enrollment
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 Pizzagalli, PhD
role: Principal Investigator
affiliation: Mclean Hospital
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Mclean Hospital
investigator full name: Diego A. Pizzagalli
investigator title: Associate Professor, Department of Psychiatry, Harvard Medical School
mesh term: Anhedonia
mesh term: Depression
mesh term: Depressive Disorder
mesh term: Depressive Disorder, Major