<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/NCT03037060</url>
  </required_header>
  <id_info>
    <org_study_id>052/2016</org_study_id>
    <nct_id>NCT03037060</nct_id>
  </id_info>
  <brief_title>Exploring Regulation and Function of Dopamine D3 Receptors in Alcohol Use Disorders: A [11C]-(+)-PHNO Study</brief_title>
  <official_title>Exploring Regulation and Function of Dopamine D3 Receptors in Alcohol Use Disorders: A [11C]-(+)-PHNO Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Centre for Addiction and Mental Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Centre for Addiction and Mental Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      There is a need to better understand the mechanisms underlying alcohol use and dependence in&#xD;
      order to advance the clinical treatment of alcohol dependence. Here, the investigators will&#xD;
      use Positron Emission Tomography to determine if there is an up-regulation of D3 receptors in&#xD;
      the brains of subjects with alcohol use disorders. The investigators will also investigate&#xD;
      the relationship between D3 binding and major phenotypes associated with alcohol use&#xD;
      disorders, namely: alcohol cue induced craving and motivation to self-administer alcohol in&#xD;
      the laboratory.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Alcohol dependence is a devastating illness with social and medical costs estimated to be 180&#xD;
      billion dollars annually in the US. In the clinical treatment of alcoholism, reducing alcohol&#xD;
      consumption in heavy drinkers is a major clinical challenge. As such, there has been much&#xD;
      emphasis in both clinical and preclinical research to identify the substrates that mediate&#xD;
      craving, excessive drinking and addiction. Identifying the neurobiological mechanisms of&#xD;
      alcohol dependence may lead to the development of new and better treatment strategies.&#xD;
      Preclinical studies indicate that the D3 receptor is involved in alcohol-cue response and in&#xD;
      the motivation to drink alcohol. However, there is currently no data available in human&#xD;
      subjects exploring the relationship between D3 and those behavioral responses in subjects&#xD;
      with alcohol use disorders.&#xD;
&#xD;
      Aim #1: To measure the [11C]-(+)-PHNO PET binding levels in the brains of subjects with&#xD;
      alcohol use disorders.&#xD;
&#xD;
      Aim #2: To determine the relationship between D3 receptor binding and alcohol cue induced&#xD;
      craving and motivation to self-administer alcohol in the laboratory.&#xD;
&#xD;
      To achieve designated goals, the investigators will recruit 25 male and female subjects who&#xD;
      are non-treatment seekers. After a period of abstinence from alcohol, participants will come&#xD;
      to the Centre for Addiction of Mental Health for a [11C]-(+)-PHNO PET scan. Participants will&#xD;
      also have additional sessions during which other alcohol-related measures will be assessed&#xD;
      (i.e. alcohol cue induced craving and motivation to self-administer alcohol in the&#xD;
      laboratory).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">December 2016</start_date>
  <completion_date type="Actual">August 2020</completion_date>
  <primary_completion_date type="Actual">August 2020</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>Dopamine D2/D3 receptor occupancy</measure>
    <time_frame>One PET scan after 2-7 days of abstinence from alcohol; ~2 hours in duration.</time_frame>
    <description>Dopamine D2/D3 receptor occupancy in the brains of individuals with Alcohol Use Disorders will be quantified using [11C]-(+)-PHNO Positron Emission Tomography (PET). [11C]-(+)-PHNO binding levels will be used to infer receptor occupancy.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Alcohol craving ratings</measure>
    <time_frame>Cue paradigm session is expected to take ~1 hour and will occur on the PET day.</time_frame>
    <description>Participants' ratings for alcohol craving acquired during the validated Cue-Induced Craving Paradigm (using the Alcohol Urge Questionnaire: 8 items on a 11-point Likert scale) will be correlated to dopamine receptor occupancy (outcome 1).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Effort to obtain alcohol</measure>
    <time_frame>Single self-administration session will occur on its own day with a time commitment of ~6 hours.</time_frame>
    <description>Laboratory alcohol self-administration paradigm in which participants press a button to intravenously self-administer small doses of alcohol will be used to assess amount of effort expended to obtain alcohol (&quot;break point&quot;). The # of button presses required to obtain the alcohol will increase as per the Progressive Ratio schedule. Regression analysis between effort and [11C]-(+)-PHNO binding (outcome 1) will be applied.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Alcohol Use Disorder</condition>
  <arm_group>
    <arm_group_label>Experimental</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>5 experimental sessions per participant:&#xD;
(1) [11C]-(+)-PHNO PET scan, (2), Alcohol Self-Administration, (3) Craving Task, (4) MRI scan and (5) Neuropsychological Assessment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>[11C]-(+)-PHNO PET scan</intervention_name>
    <description>PET scan</description>
    <arm_group_label>Experimental</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Alcohol Self-Administration</intervention_name>
    <description>Session for assessing motivation for consuming alcohol.</description>
    <arm_group_label>Experimental</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Craving Task</intervention_name>
    <description>Cue exposure paradigm</description>
    <arm_group_label>Experimental</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>MRI scan</intervention_name>
    <description>MRI scan scan to analyze the PET data will be administered.</description>
    <arm_group_label>Experimental</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Neuropsychological Assessment</intervention_name>
    <description>Cognitive questionnaires administered over course of study.</description>
    <arm_group_label>Experimental</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects will meet diagnostic criteria for alcohol use disorder (mild through severe).&#xD;
&#xD;
          -  Willing to abstain from drugs and alcohol prior to study visits&#xD;
&#xD;
          -  A negative urine screen for illicit psychoactive drug use&#xD;
&#xD;
          -  Willing and capable to provide written informed consent&#xD;
&#xD;
          -  Willing to participate in cue exposure and intravenous alcohol administration sessions&#xD;
&#xD;
          -  Male and female adults (at least 19 years old)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  DSM diagnosis of drug dependence other than alcohol&#xD;
&#xD;
          -  Any severe Axis I disorder aside from alcohol use disorder&#xD;
&#xD;
          -  Any medical condition requiring immediate investigation&#xD;
&#xD;
          -  History of seizures, past or current neurological illness or serious head trauma&#xD;
&#xD;
          -  Suicidal ideation&#xD;
&#xD;
          -  Pregnancy tested by urine or blood screen or lactation&#xD;
&#xD;
          -  Current past or anticipated exposure to radiation exceeding permissible limits as set&#xD;
             by the CAMH PET Centre&#xD;
&#xD;
          -  Metal implants or paramagnetic objects within the body which may interfere with the&#xD;
             MRI&#xD;
&#xD;
          -  Claustrophobia or a history of panic attacks&#xD;
&#xD;
          -  Any other problem that, in the investigators' opinion, would preclude participation in&#xD;
             trial (i.e., complicated withdrawal).&#xD;
&#xD;
          -  Currently seeking treatment or attempting to reduce/quit drinking&#xD;
&#xD;
          -  History of negative responses to venipuncture procedures (e.g., fainting/vasovagal&#xD;
             response)&#xD;
&#xD;
          -  Medications or medical disorders for which alcohol consumption is contraindicated&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bernard Le Foll, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Centre for Addiction and Mental Health</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Centre for Addiction and Mental Health</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5S2S1</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <link>
    <url>http://www.camh.net/research</url>
    <description>Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collaborating Centre.</description>
  </link>
  <verification_date>October 2020</verification_date>
  <study_first_submitted>January 16, 2017</study_first_submitted>
  <study_first_submitted_qc>January 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 31, 2017</study_first_posted>
  <last_update_submitted>October 27, 2020</last_update_submitted>
  <last_update_submitted_qc>October 27, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">October 29, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Centre for Addiction and Mental Health</investigator_affiliation>
    <investigator_full_name>Bernard Le Foll</investigator_full_name>
    <investigator_title>Principal Investigator, MD, PhD, CCFP</investigator_title>
  </responsible_party>
  <keyword>Alcohol use, problem</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Alcohol Drinking</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/NCT03037060
org study id: 052/2016
nct id: NCT03037060
lead sponsor: 
has dmc: No
There is a need to better understand the mechanisms underlying alcohol use and dependence in
      order to advance the clinical treatment of alcohol dependence. Here, the investigators will
      use Positron Emission Tomography to determine if there is an up-regulation of D3 receptors in
      the brains of subjects with alcohol use disorders. The investigators will also investigate
      the relationship between D3 binding and major phenotypes associated with alcohol use
      disorders, namely: alcohol cue induced craving and motivation to self-administer alcohol in
      the laboratory.
Alcohol dependence is a devastating illness with social and medical costs estimated to be 180
      billion dollars annually in the US. In the clinical treatment of alcoholism, reducing alcohol
      consumption in heavy drinkers is a major clinical challenge. As such, there has been much
      emphasis in both clinical and preclinical research to identify the substrates that mediate
      craving, excessive drinking and addiction. Identifying the neurobiological mechanisms of
      alcohol dependence may lead to the development of new and better treatment strategies.
      Preclinical studies indicate that the D3 receptor is involved in alcohol-cue response and in
      the motivation to drink alcohol. However, there is currently no data available in human
      subjects exploring the relationship between D3 and those behavioral responses in subjects
      with alcohol use disorders.

      Aim #1: To measure the [11C]-(+)-PHNO PET binding levels in the brains of subjects with
      alcohol use disorders.

      Aim #2: To determine the relationship between D3 receptor binding and alcohol cue induced
      craving and motivation to self-administer alcohol in the laboratory.

      To achieve designated goals, the investigators will recruit 25 male and female subjects who
      are non-treatment seekers. After a period of abstinence from alcohol, participants will come
      to the Centre for Addiction of Mental Health for a [11C]-(+)-PHNO PET scan. Participants will
      also have additional sessions during which other alcohol-related measures will be assessed
      (i.e. alcohol cue induced craving and motivation to self-administer alcohol in the
      laboratory).
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Dopamine D2/D3 receptor occupancy
time frame: One PET scan after 2-7 days of abstinence from alcohol; ~2 hours in duration.
description: Dopamine D2/D3 receptor occupancy in the brains of individuals with Alcohol Use Disorders will be quantified using [11C]-(+)-PHNO Positron Emission Tomography (PET). [11C]-(+)-PHNO binding levels will be used to infer receptor occupancy.
measure: Alcohol craving ratings
time frame: Cue paradigm session is expected to take ~1 hour and will occur on the PET day.
description: Participants' ratings for alcohol craving acquired during the validated Cue-Induced Craving Paradigm (using the Alcohol Urge Questionnaire: 8 items on a 11-point Likert scale) will be correlated to dopamine receptor occupancy (outcome 1).
measure: Effort to obtain alcohol
time frame: Single self-administration session will occur on its own day with a time commitment of ~6 hours.
description: Laboratory alcohol self-administration paradigm in which participants press a button to intravenously self-administer small doses of alcohol will be used to assess amount of effort expended to obtain alcohol ("break point"). The # of button presses required to obtain the alcohol will increase as per the Progressive Ratio schedule. Regression analysis between effort and [11C]-(+)-PHNO binding (outcome 1) will be applied.
arm group label: Experimental
arm group type: Experimental
description: 5 experimental sessions per participant:
(1) [11C]-(+)-PHNO PET scan, (2), Alcohol Self-Administration, (3) Craving Task, (4) MRI scan and (5) Neuropsychological Assessment.
intervention type: Other
intervention name: [11C]-(+)-PHNO PET scan
description: PET scan
arm group label: Experimental
intervention type: Other
intervention name: Alcohol Self-Administration
description: Session for assessing motivation for consuming alcohol.
arm group label: Experimental
intervention type: Other
intervention name: Craving Task
description: Cue exposure paradigm
arm group label: Experimental
intervention type: Other
intervention name: MRI scan
description: MRI scan scan to analyze the PET data will be administered.
arm group label: Experimental
intervention type: Other
intervention name: Neuropsychological Assessment
description: Cognitive questionnaires administered over course of study.
arm group label: Experimental
criteria: 
gender: All
minimum age: 19 Years
maximum age: N/A
healthy volunteers: No
last name: Bernard Le Foll, MD, PhD
role: Principal Investigator
affiliation: Centre for Addiction and Mental Health
facility: 
country: Canada
url: http://www.camh.net/research
description: Information about research at the Centre for Addiction and Mental Health, Canada's largest mental health and addiction teaching hospital, fully affiliated with the University of Toronto, and a PAHO/WHO Collaborating Centre.
responsible party type: Principal Investigator
investigator affiliation: Centre for Addiction and Mental Health
investigator full name: Bernard Le Foll
investigator title: Principal Investigator, MD, PhD, CCFP
mesh term: Alcoholism
mesh term: Alcohol Drinking
sharing ipd: No