<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/NCT03244592</url>
  </required_header>
  <id_info>
    <org_study_id>K01AA026005</org_study_id>
    <secondary_id>K01AA026005</secondary_id>
    <nct_id>NCT03244592</nct_id>
  </id_info>
  <brief_title>Minocycline for Alcohol Use Disorder</brief_title>
  <official_title>Development of Minocycline as a Neuroimmune Therapy for Alcohol Use Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, Los Angeles</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute on Alcohol Abuse and Alcoholism (NIAAA)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, Los Angeles</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this proposal is to advance medication development for alcohol use disorder&#xD;
      by examining the efficacy and mechanisms of action of minocycline, a neuroimmune modulator,&#xD;
      as a potential treatment. This study has important clinical implications, as the available&#xD;
      treatments for alcohol use disorder are only modestly effective and testing novel medications&#xD;
      is a high research priority.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The research objective of this project is to advance medication development for AUD by&#xD;
      conducting a randomized, double blind, placebo-controlled, neuroimaging study to examine the&#xD;
      effects of minocycline on neuroinflammation, alcohol cue reactivity, neurocognitive&#xD;
      performance, and alcohol use. In the proposed study, non-treatment seeking individuals with a&#xD;
      current DSM-5 AUD diagnosis (N = 32) will be randomized to receive either 200 mg of&#xD;
      minocycline per day or placebo for 28 days and complete two laboratory sessions. The first&#xD;
      laboratory session will be performed immediately before commencing the medication regimen&#xD;
      (day 0) and the second will be completed after taking the medication daily for 28 days.&#xD;
      Within each laboratory session, participants will complete a cue reactivity paradigm,&#xD;
      neurocognitive performance tasks, and a positron emission tomography (PET) imaging session.&#xD;
      Neuroinflammation will be assessed by using PET imaging with the radiotracer&#xD;
      N-(2,5-dimethoxy-benzyl)-N-(5-fluoro-2-phenoxyphenyl) acetamide, labeled with carbon-11&#xD;
      ([11C]-DAA1106), which binds to the mitochondrial translocator protein, a marker of activated&#xD;
      microglia in brain. Additionally, blood samples will be drawn on days 0, 7, 14, 21, and 28 to&#xD;
      measure circulating levels of proinflammatory markers and alcohol use over the four weeks of&#xD;
      treatment will also be measured.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Investigator left institution prior to enrollment of study participants&#xD;
  </why_stopped>
  <start_date type="Anticipated">January 15, 2018</start_date>
  <completion_date type="Actual">March 1, 2018</completion_date>
  <primary_completion_date type="Actual">March 1, 2018</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Investigator, Outcomes Assessor)</masking>
    <masking_description>Double Blind</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Microglial Activation</measure>
    <time_frame>Change from baseline after 28 days of medication dosing</time_frame>
    <description>Level of [11C]DAA1106 binding during PET imaging</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cue-Induced Alcohol Craving</measure>
    <time_frame>Change from baseline after 28 days of medication dosing</time_frame>
    <description>Alcohol Urge Questionnaire (AUQ)</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Alcohol consumption</measure>
    <time_frame>Day 28 of medication dosing period</time_frame>
    <description>Total drinks consumed</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Verbal Learning and Memory</measure>
    <time_frame>Change from baseline after 28 days of medication dosing</time_frame>
    <description>Hopkins Verbal Learning Test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Set-Shifting</measure>
    <time_frame>Change from baseline after 28 days of medication dosing</time_frame>
    <description>Wisconsin Card Sorting Test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Response Inhibition</measure>
    <time_frame>Change from baseline after 28 days of medication dosing</time_frame>
    <description>Stop Signal Task</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Manipulative Dexterity</measure>
    <time_frame>Change from baseline after 28 days of medication dosing</time_frame>
    <description>Grooved Pegboard Test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Executive Function</measure>
    <time_frame>Change from baseline after 28 days of medication dosing</time_frame>
    <description>Digit Symbol Substitution Test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Memory</measure>
    <time_frame>Change from baseline after 28 days of medication dosing</time_frame>
    <description>Digit Span</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Vocabulary</measure>
    <time_frame>Change from baseline after 28 days of medication dosing</time_frame>
    <description>WAIS Vocabulary</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Executive Function</measure>
    <time_frame>Change from baseline after 28 days of medication dosing</time_frame>
    <description>Rey Complex Figure Copy</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Peripheral Proinflammatory Marker levels</measure>
    <time_frame>At baseline (day zero) and after 7, 14, and 21 and 28 days of medication dosing</time_frame>
    <description>Serum level of cytokines and innate immune receptors</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Alcohol Use Disorder Severity</measure>
    <time_frame>At baseline (day zero) and after 28 days of medication dosing</time_frame>
    <description>Symptom count from the alcohol module for the Structured Clinical Interview for DSM-5</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Alcohol Use Disorder</condition>
  <condition>Inflammation</condition>
  <condition>Neurocognitive Dysfunction</condition>
  <condition>Craving</condition>
  <condition>Alcohol Drinking</condition>
  <arm_group>
    <arm_group_label>Minocycline</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>200 mg/day</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sugar Pill</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Matched placebo</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Minocycline</intervention_name>
    <description>200 mg/day</description>
    <arm_group_label>Minocycline</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sugar pill</intervention_name>
    <description>Matched placebo</description>
    <arm_group_label>Sugar Pill</arm_group_label>
    <other_name>Placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Ages 25 - 45&#xD;
&#xD;
          2. Meet DSM-5 diagnostic criteria for an AUD [n.b., only participants with moderate or&#xD;
             severe AUD will be enrolled]&#xD;
&#xD;
          3. Drink ≥ 48 standard drinks in a 30-day period before enrollment&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Currently in treatment for AUD, a history of treatment in the 30 days before&#xD;
             enrollment, or currently treatment seeking&#xD;
&#xD;
          2. Current (last 12 months) DSM-V diagnosis of substance use disorder for any&#xD;
             psychoactive substances other than alcohol and nicotine&#xD;
&#xD;
          3. Lifetime DSM-V diagnosis of schizophrenia, bipolar disorder, or any psychotic disorder&#xD;
&#xD;
          4. Positive urine screen for narcotics, amphetamines, or sedative hypnotics&#xD;
&#xD;
          5. Serious alcohol withdrawal symptoms as indicated by a score ≥ 10 on the Clinical&#xD;
             Institute Withdrawal Assessment for Alcohol-Revised&#xD;
&#xD;
          6. Pregnancy, nursing, or refusal to use reliable method of birth control (if female)&#xD;
&#xD;
          7. A medical condition that may interfere with safe study participation (e.g., unstable&#xD;
             cardiac, renal, or liver disease, uncontrolled hypertension or diabetes)&#xD;
&#xD;
          8. AST, ALT, or GGT ≥ 3 times upper normal limit&#xD;
&#xD;
          9. Attempted suicide in the past 3 years and/or serious suicidal intention or plan within&#xD;
             the past year&#xD;
&#xD;
         10. Currently on prescription medication that contraindicates use of MINO&#xD;
&#xD;
         11. Any other circumstances that, in the opinion of the investigators, compromises&#xD;
             participant safety.&#xD;
&#xD;
         12. Claustrophobia&#xD;
&#xD;
         13. Participating in any other research study involving exposure to ionizing radiation in&#xD;
             the past year will be excluded if the total cumulative exposure from the past research&#xD;
             studies and the current research study would exceed the limits set by the FDA in 21&#xD;
             CFR 361.1. Specifically, the total cumulated dose to the whole body, active&#xD;
             blood-forming organs, lens of the eye, and gonads must remain below 5 rems, and the&#xD;
             cumulated dose to all other organs must remain below 15 rems. Potential participants&#xD;
             who have had exposure to ionizing radiation in the past year will not be allowed to&#xD;
             participate if we are unable to obtain proper documentation quantifying the amount of&#xD;
             past exposure.&#xD;
&#xD;
         14. Presence of a metal device in the body (e.g., pacemaker, infusion pump, aneurysm clip,&#xD;
             metal prosthesis or plate): Those devices could either interfere with the acquisition&#xD;
             of the MRI scan of the brain or for whom the MRI scan would pose a potential risk. If&#xD;
             participants have a non-removable device in their body, they must acquire and show a&#xD;
             document exhibiting the device is MRI-compatible.&#xD;
&#xD;
         15. low affinity rs6971 genotype&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Daniel Roche, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, Los Angeles</affiliation>
  </overall_official>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>July 28, 2017</study_first_submitted>
  <study_first_submitted_qc>August 6, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 9, 2017</study_first_posted>
  <last_update_submitted>January 22, 2019</last_update_submitted>
  <last_update_submitted_qc>January 22, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">January 24, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Minocycline</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Alcohol Drinking</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Minocycline</mesh_term>
  </intervention_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/NCT03244592
org study id: K01AA026005
secondary id: K01AA026005
nct id: NCT03244592
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The objective of this proposal is to advance medication development for alcohol use disorder
      by examining the efficacy and mechanisms of action of minocycline, a neuroimmune modulator,
      as a potential treatment. This study has important clinical implications, as the available
      treatments for alcohol use disorder are only modestly effective and testing novel medications
      is a high research priority.
The research objective of this project is to advance medication development for AUD by
      conducting a randomized, double blind, placebo-controlled, neuroimaging study to examine the
      effects of minocycline on neuroinflammation, alcohol cue reactivity, neurocognitive
      performance, and alcohol use. In the proposed study, non-treatment seeking individuals with a
      current DSM-5 AUD diagnosis (N = 32) will be randomized to receive either 200 mg of
      minocycline per day or placebo for 28 days and complete two laboratory sessions. The first
      laboratory session will be performed immediately before commencing the medication regimen
      (day 0) and the second will be completed after taking the medication daily for 28 days.
      Within each laboratory session, participants will complete a cue reactivity paradigm,
      neurocognitive performance tasks, and a positron emission tomography (PET) imaging session.
      Neuroinflammation will be assessed by using PET imaging with the radiotracer
      N-(2,5-dimethoxy-benzyl)-N-(5-fluoro-2-phenoxyphenyl) acetamide, labeled with carbon-11
      ([11C]-DAA1106), which binds to the mitochondrial translocator protein, a marker of activated
      microglia in brain. Additionally, blood samples will be drawn on days 0, 7, 14, 21, and 28 to
      measure circulating levels of proinflammatory markers and alcohol use over the four weeks of
      treatment will also be measured.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
masking description: Double Blind
measure: Microglial Activation
time frame: Change from baseline after 28 days of medication dosing
description: Level of [11C]DAA1106 binding during PET imaging
measure: Cue-Induced Alcohol Craving
time frame: Change from baseline after 28 days of medication dosing
description: Alcohol Urge Questionnaire (AUQ)
measure: Alcohol consumption
time frame: Day 28 of medication dosing period
description: Total drinks consumed
measure: Verbal Learning and Memory
time frame: Change from baseline after 28 days of medication dosing
description: Hopkins Verbal Learning Test
measure: Set-Shifting
time frame: Change from baseline after 28 days of medication dosing
description: Wisconsin Card Sorting Test
measure: Response Inhibition
time frame: Change from baseline after 28 days of medication dosing
description: Stop Signal Task
measure: Manipulative Dexterity
time frame: Change from baseline after 28 days of medication dosing
description: Grooved Pegboard Test
measure: Executive Function
time frame: Change from baseline after 28 days of medication dosing
description: Digit Symbol Substitution Test
measure: Memory
time frame: Change from baseline after 28 days of medication dosing
description: Digit Span
measure: Vocabulary
time frame: Change from baseline after 28 days of medication dosing
description: WAIS Vocabulary
measure: Executive Function
time frame: Change from baseline after 28 days of medication dosing
description: Rey Complex Figure Copy
measure: Peripheral Proinflammatory Marker levels
time frame: At baseline (day zero) and after 7, 14, and 21 and 28 days of medication dosing
description: Serum level of cytokines and innate immune receptors
measure: Alcohol Use Disorder Severity
time frame: At baseline (day zero) and after 28 days of medication dosing
description: Symptom count from the alcohol module for the Structured Clinical Interview for DSM-5
arm group label: Minocycline
arm group type: Active Comparator
description: 200 mg/day
arm group label: Sugar Pill
arm group type: Placebo Comparator
description: Matched placebo
intervention type: Drug
intervention name: Minocycline
description: 200 mg/day
arm group label: Minocycline
intervention type: Drug
intervention name: Sugar pill
description: Matched placebo
arm group label: Sugar Pill
other name: Placebo
criteria: 
gender: All
minimum age: 21 Years
maximum age: 55 Years
healthy volunteers: No
last name: Daniel Roche, PhD
role: Principal Investigator
affiliation: University of California, Los Angeles
responsible party type: Sponsor
mesh term: Inflammation
mesh term: Alcoholism
mesh term: Alcohol Drinking
mesh term: Cognitive Dysfunction
mesh term: Minocycline
sharing ipd: No