<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/NCT03818191</url>
  </required_header>
  <id_info>
    <org_study_id>18-006428</org_study_id>
    <secondary_id>1R01AA027486-01</secondary_id>
    <secondary_id>1U01AA027487</secondary_id>
    <nct_id>NCT03818191</nct_id>
  </id_info>
  <brief_title>Pharmacogenomics and Pharmacometabolomics of Acamprosate Treatment Outcome</brief_title>
  <official_title>Pharmacogenomics and Pharmacometabolomics of Acamprosate Treatment Outcome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mayo Clinic</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>Mayo Clinic</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>
      AUDs are difficult to treat, and relapse rates are high, with an estimated 80% of individuals&#xD;
      with AUDs returning to alcohol use after completing addictions treatment. Novel treatment&#xD;
      approaches are needed to enhance long term sobriety. The investigator's research team has&#xD;
      been investigating the use of acamprosate to prevent relapse to alcohol use. Unfortunately&#xD;
      despite being FDA approved and endorsed by the American Psychiatric Association only 10% of&#xD;
      patients treated for AUD are prescribed acamprosate or other antidipsotropic medications. The&#xD;
      number is higher for patients treated in programs affiliated with Mayo Clinic Addiction&#xD;
      Services (approximately 20%) but is way less than expected. The most common reasons behind&#xD;
      these low numbers are the understanding that not every patient benefits from the use of&#xD;
      specific medication and the lack of biomarkers predictive of response. The purpose of this&#xD;
      project is to identify such biomarkers by discovery of genomic and metabolomic markers&#xD;
      associated with response to acamprosate treatment.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 15, 2019</start_date>
  <completion_date type="Anticipated">October 2023</completion_date>
  <primary_completion_date type="Anticipated">October 2023</primary_completion_date>
  <phase>Phase 4</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>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Alcohol Timeline Follow Back</measure>
    <time_frame>will be defined as continuous sobriety (yes/no) during 3 months of treatment</time_frame>
    <description>The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Alcohol Timeline Follow Back</measure>
    <time_frame>The number of days until first alcohol use assessed by TLFB during 3 months of treatment</time_frame>
    <description>The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">800</enrollment>
  <condition>Alcohol Use Disorder</condition>
  <arm_group>
    <arm_group_label>Acamprosate</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>All participants will be randomized to receive acamprosate or placebo in a double-blinded placebo-controlled trial.&#xD;
The most common side effect associated with acamprosate use is diarrhea, which occurs in approximately 16% of patients. Other frequently occurring side effects include asthenia, nausea, pruritus, and flatulence, headache, abdominal pain, flu syndrome, edema, weight gain, and myalgia.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>All participants will be randomized to receive acamprosate or placebo in a double-blinded placebo-controlled trial.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acamprosate</intervention_name>
    <description>The research pharmacy contracted for this study will randomize the study participants for all sites with placebo or acamprosate.</description>
    <arm_group_label>Acamprosate</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>The research pharmacy contracted for this study will randomize the study participants for all sites with placebo or acamprosate.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Age 18 to85; DSM-5 diagnosis of AUD determined by PRISM;&#xD;
&#xD;
          2. Completion of alcohol detoxification (CIWA score &lt; 5) and no alcohol for at least 7&#xD;
             days (but no more than 35 days);&#xD;
&#xD;
          3. Ability to provide informed consent&#xD;
&#xD;
          4. Ability to speak English&#xD;
&#xD;
          5. Willingness to use the study medications for 3 months and attend follow-up visits.&#xD;
&#xD;
          6. No chronic/daily use of benzodiazepines, opioids, or stimulants for a period of time&#xD;
             which is determined by 3 x the medication half-life value (see addendum A) to be&#xD;
             completed before the initiation of study medication (acamprosate or placebo).&#xD;
&#xD;
          7. Willingness to discontinue previously prescribed acamprosate for a period of at least&#xD;
             3 days before randomization to study medication (acamprosate or placebo).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hypersensitivity or allergy to acamprosate&#xD;
&#xD;
          2. Current use of wellbutrin and not willing to switch to an acceptable antidepressant&#xD;
             medication&#xD;
&#xD;
          3. Renal impairment (creatinine level &gt;1.5 mg/dL);&#xD;
&#xD;
          4. Diagnosis of advanced liver disease indicated in the medical record or by a MELD score&#xD;
             of above 10;&#xD;
&#xD;
          5. Women who are pregnant, breastfeeding, or planning to become pregnant during the next&#xD;
             year;&#xD;
&#xD;
          6. Primary diagnosis of substance use disorder other than alcohol as determined by PRISM&#xD;
             or in medical record review or secondary diagnosis of active (within the past year)&#xD;
             benzo/sedative dependence, opioid dependence, stimulant dependence, heroin dependence,&#xD;
             and/or cocaine dependence&#xD;
&#xD;
          7. Refusal to abstain from any chronic/daily use of prescribed benzodiazepines, opioids,&#xD;
             stimulants, cannabis related medication such as CBD or medical marijuana, during the&#xD;
             course of participation.&#xD;
&#xD;
          8. Current use of Naltrexone and not willing to stop and switch to Acamprosate/Placebo&#xD;
&#xD;
          9. Current use of Antabuse.&#xD;
&#xD;
         10. Active suicidal ideation or any unstable medical or psychiatric condition as&#xD;
             determined by responses to PRISM or by the investigator.&#xD;
&#xD;
         11. Status of involuntary or court-ordered admission at time of consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Victor M Karpyak, MD, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Mayo Clinic</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Hazelden Betty Ford Foundation</name>
      <address>
        <city>Center City</city>
        <state>Minnesota</state>
        <zip>55012</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Frank Markie</last_name>
      <phone>651-213-4456</phone>
      <email>fmarkie@hazeldenbettyford.org</email>
    </contact>
    <investigator>
      <last_name>Cedric Skillon, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Mayo Clinic in Rochester</name>
      <address>
        <city>Rochester</city>
        <state>Minnesota</state>
        <zip>55905</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Kristina Dammen</last_name>
      <phone>507-255-0761</phone>
      <email>dammen.kristina@mayo.edu</email>
    </contact>
    <contact_backup>
      <last_name>Jared Masrud</last_name>
      <phone>507-255-0001</phone>
      <email>masrud.jared@mayo.edu</email>
    </contact_backup>
    <investigator>
      <last_name>Victor M Karpyak</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location>
    <facility>
      <name>Hazelden Betty Ford Foundation</name>
      <address>
        <city>Newberg</city>
        <state>Oregon</state>
        <zip>97132</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ivana Ortega</last_name>
      <phone>503-554-7904</phone>
      <email>IOrtega@hazeldenbettyford.org</email>
    </contact>
    <investigator>
      <last_name>Cedric Skillon, MD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>https://www.mayo.edu/research/clinical-trials</url>
    <description>Mayo Clinic Clinical Trials</description>
  </link>
  <verification_date>August 2023</verification_date>
  <study_first_submitted>January 14, 2019</study_first_submitted>
  <study_first_submitted_qc>January 25, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 28, 2019</study_first_posted>
  <last_update_submitted>August 1, 2023</last_update_submitted>
  <last_update_submitted_qc>August 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">August 3, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Mayo Clinic</investigator_affiliation>
    <investigator_full_name>Victor M. Karpyak</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Acamprosate</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/NCT03818191
org study id: 18-006428
secondary id: 1R01AA027486-01
secondary id: 1U01AA027487
nct id: NCT03818191
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
AUDs are difficult to treat, and relapse rates are high, with an estimated 80% of individuals
      with AUDs returning to alcohol use after completing addictions treatment. Novel treatment
      approaches are needed to enhance long term sobriety. The investigator's research team has
      been investigating the use of acamprosate to prevent relapse to alcohol use. Unfortunately
      despite being FDA approved and endorsed by the American Psychiatric Association only 10% of
      patients treated for AUD are prescribed acamprosate or other antidipsotropic medications. The
      number is higher for patients treated in programs affiliated with Mayo Clinic Addiction
      Services (approximately 20%) but is way less than expected. The most common reasons behind
      these low numbers are the understanding that not every patient benefits from the use of
      specific medication and the lack of biomarkers predictive of response. The purpose of this
      project is to identify such biomarkers by discovery of genomic and metabolomic markers
      associated with response to acamprosate treatment.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Alcohol Timeline Follow Back
time frame: will be defined as continuous sobriety (yes/no) during 3 months of treatment
description: The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date.
measure: Alcohol Timeline Follow Back
time frame: The number of days until first alcohol use assessed by TLFB during 3 months of treatment
description: The Alcohol Timeline Follow Back (TLFB) is a drinking assessment method that obtains estimates of daily drinking and has been evaluated with clinical and nonclinical populations. Using a calendar, people provide retrospective estimates of their daily drinking over a specified time period that can vary up to 12 months from the interview date.
arm group label: Acamprosate
arm group type: Active Comparator
description: All participants will be randomized to receive acamprosate or placebo in a double-blinded placebo-controlled trial.
The most common side effect associated with acamprosate use is diarrhea, which occurs in approximately 16% of patients. Other frequently occurring side effects include asthenia, nausea, pruritus, and flatulence, headache, abdominal pain, flu syndrome, edema, weight gain, and myalgia.
arm group label: Placebo
arm group type: Placebo Comparator
description: All participants will be randomized to receive acamprosate or placebo in a double-blinded placebo-controlled trial.
intervention type: Drug
intervention name: Acamprosate
description: The research pharmacy contracted for this study will randomize the study participants for all sites with placebo or acamprosate.
arm group label: Acamprosate
intervention type: Other
intervention name: Placebo
description: The research pharmacy contracted for this study will randomize the study participants for all sites with placebo or acamprosate.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Victor M Karpyak, MD, Ph.D.
role: Principal Investigator
affiliation: Mayo Clinic
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
contact backup: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
url: https://www.mayo.edu/research/clinical-trials
description: Mayo Clinic Clinical Trials
responsible party type: Principal Investigator
investigator affiliation: Mayo Clinic
investigator full name: Victor M. Karpyak
investigator title: Principal Investigator
mesh term: Alcoholism
mesh term: Acamprosate
sharing ipd: No