<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/NCT03278886</url>
  </required_header>
  <id_info>
    <org_study_id>H-36491</org_study_id>
    <secondary_id>UH2AA026193</secondary_id>
    <nct_id>NCT03278886</nct_id>
  </id_info>
  <brief_title>St. PETERsburg Pain and Alcohol Intervention With Naltrexone and Nalmefene</brief_title>
  <acronym>PETER PAIN</acronym>
  <official_title>Pilot Study of Opioid-receptor Antagonists to Reduce Pain and Inflammation Among HIV-Infected Persons With Alcohol Problems</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Boston Medical Center</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>Boston Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study is a randomized controlled trial (RCT) to assess the feasibility, tolerability,&#xD;
      and safety of using opioid receptor antagonists (naltrexone and nalmefene) to treat pain&#xD;
      among HIV-infected persons with heavy alcohol use and chronic pain.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Pain is a common co-morbidity for HIV-infected patients. Prevalence studies suggest that, on&#xD;
      average, half of all HIV-infected persons suffer pain. Chronic pain can lead to heavy alcohol&#xD;
      use among HIV-infected persons, which may in turn be a barrier to treatment/control of HIV&#xD;
      and contribute to spread of HIV. Thus there is an urgent need to address pain among persons&#xD;
      with HIV. Opioid receptor antagonists such as naltrexone and nalmefene, which are licensed&#xD;
      for treatment of alcohol use disorders, show promise as being effective and safe treatments&#xD;
      for chronic pain among persons with HIV. This study will pilot test novel pharmacotherapies&#xD;
      (opioid receptor antagonists) to improve chronic pain among HIV-infected heavy drinkers. The&#xD;
      specific aims of the research is to assess the feasibility, tolerability and safety of using&#xD;
      opioid receptor antagonists (low-dose naltrexone and nalmefene) to treat pain among&#xD;
      HIV-infected persons with heavy alcohol use and chronic pain.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 3, 2018</start_date>
  <completion_date type="Actual">December 19, 2018</completion_date>
  <primary_completion_date type="Actual">December 19, 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>
  </study_design_info>
  <primary_outcome>
    <measure>Medication Tolerability Measured Via a 0-100 Visual Analog Scale</measure>
    <time_frame>Primary endpoint at 8 weeks</time_frame>
    <description>Medication tolerability will be measured via a 0-100 visual analog scale. Participants will be asked to indicate on a scale of 0-100, how well they have tolerated the study medication with 0 anchored as &quot;cannot tolerate at all&quot; and 100 as &quot;tolerate perfectly well.&quot; Higher numbers will be indicative of higher tolerability of the medication.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Alcohol Use Defined as a Change in the Mean Number of Grams of Pure Ethanol Consumed Per Day From Baseline to 8 Weeks</measure>
    <time_frame>Baseline, 8 weeks</time_frame>
    <description>Measured via 30 Day Alcohol Use Timeline Follow Back Method</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Treatment Discontinuation Defined as Patient Self-report of Stopping Medication Anytime During the Treatment Period</measure>
    <time_frame>4 weeks, 8 weeks</time_frame>
    <description>Measured via one question asking participants if they had discontinued medication since their last visit. Assessed at 4 and 8 week study visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Adherence to Medication Defined as Self-report of Percentage of Study Medication Taken in the Past Two Weeks</measure>
    <time_frame>Endpoint at 8 weeks</time_frame>
    <description>Measured by participants' drawing a line on a a Visual Analog Scale, which ranges from 0 to 100. Higher numbers indicate higher adherence to study medication.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Adherence Assessed Via Riboflavin in the Urine Confirming Adherence</measure>
    <time_frame>Endpoint at 8 weeks</time_frame>
    <description>Measured through visual inspection of the urine for the presence or absence of riboflavin using ultraviolet (UV) light at the long wave setting (33 mm) in a room with low ambient light.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question</measure>
    <time_frame>2 weeks, 4 weeks, 6 weeks, 8 weeks</time_frame>
    <description>Measured via a 16-item symptom checklist with the option for participants to report any experienced side effects not on the checklist. Side effect severity is rated by trained research assessors. The checklist is asked at 2, 4, 6, and 8-week study visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medication Satisfaction Defined as a Score From 0-100 Measured Via the Treatment Satisfaction Questionnaire for Medication (TSQM), With Higher Scores Corresponding to Higher Treatment Satisfaction.</measure>
    <time_frame>4 weeks, 8 weeks</time_frame>
    <description>Measured via using the 14-item Treatment Satisfaction Questionnaire, which consists of 14 items that result in four domains: Effectiveness, Side Effects, Convenience and Global Satisfaction. Higher scores indicate greater satisfaction with medication. Assessed at 4 and 8 week study visits.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Severe Hepatotoxicity Defined as AST/ALT &gt;10X the Level of Normal</measure>
    <time_frame>Endpoint at 8 weeks</time_frame>
    <description>Aminotransferase levels (AST/ALT) are tested to look for severe hepatotoxicity defined as AST/ALT &gt; 10 times the level of normal.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">11</enrollment>
  <condition>HIV Infection</condition>
  <condition>Alcohol Use</condition>
  <condition>Pain</condition>
  <arm_group>
    <arm_group_label>Low dose naltrexone</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Nalmefene</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Low dose naltrexone</intervention_name>
    <description>4.5 mg of low dose naltrexone taken once daily for 8 weeks</description>
    <arm_group_label>Low dose naltrexone</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nalmefene</intervention_name>
    <description>18 mg of nalmefene taken once daily for 8 weeks</description>
    <arm_group_label>Nalmefene</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years or older&#xD;
&#xD;
          -  HIV-positive&#xD;
&#xD;
          -  Chronic pain (present ≥3 mo) of moderate to severe intensity&#xD;
&#xD;
          -  Heavy drinking past year (Based on NIAAA criteria: &gt; 14 standard drinks per week/ &gt; 4&#xD;
             drinks in a day for men; &gt; 7 drinks in the past week/ &gt; 3 drinks in a day for women)&#xD;
&#xD;
          -  If female, negative pregnancy test and willing to use adequate birth control&#xD;
&#xD;
          -  Provision of contact information for 2 contacts to assist with follow-up&#xD;
&#xD;
          -  Stable address within 100 kilometers of St. Petersburg&#xD;
&#xD;
          -  Possession of a telephone (home or cell)&#xD;
&#xD;
          -  Able and willing to comply with all study protocols and procedures&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Not fluent in Russian&#xD;
&#xD;
          -  Cognitive impairment resulting in inability to provide informed consent based on&#xD;
             research assessor (RA) assessment&#xD;
&#xD;
          -  Known active TB or current febrile illness&#xD;
&#xD;
          -  Breastfeeding&#xD;
&#xD;
          -  Uncontrolled psychiatric illness (such as active psychosis) (i.e., answered yes to any&#xD;
             of the following: past three month active hallucinations; mental health symptoms&#xD;
             prompting a visit to the ED or hospital)&#xD;
&#xD;
          -  History of hypersensitivity to naltrexone, nalmefene, or naloxone&#xD;
&#xD;
          -  Current use (past week) of illicit or prescribed opiates as documented by either&#xD;
             self-report or positive urine drug test&#xD;
&#xD;
          -  Unwilling to abstain from opiates during the treatment period&#xD;
&#xD;
          -  Current use of neuroleptics&#xD;
&#xD;
          -  History of seizure disorder&#xD;
&#xD;
          -  Known liver failure&#xD;
&#xD;
          -  ALT/AST levels &gt;5x normal&#xD;
&#xD;
          -  History of Raynaud's Disease&#xD;
&#xD;
          -  Planned surgeries in the next three months&#xD;
&#xD;
          -  Enrolled in another HIV and/or substance use medication intervention study&#xD;
&#xD;
          -  Taking naltrexone in the past 30 days&#xD;
&#xD;
          -  Taking nalmefene in the past 30 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeffrey H. Samet, MD, MA, MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Boston University/Boston Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>First St. Petersburg Pavlov State Medical University</name>
      <address>
        <city>St. Petersburg</city>
        <zip>197022</zip>
        <country>Russian Federation</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Russian Federation</country>
  </location_countries>
  <link>
    <url>http://www.urbanarch.org</url>
    <description>URBAN ARCH, a member of NIAAA CHAART (Consortiums for HIV/AIDS &amp; Alcohol Research Translation) initiative, conducts and disseminates interdisciplinary research on how alcohol impacts people with HIV and develops interventions to reduce related outcomes.</description>
  </link>
  <verification_date>August 2020</verification_date>
  <study_first_submitted>September 5, 2017</study_first_submitted>
  <study_first_submitted_qc>September 8, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 12, 2017</study_first_posted>
  <results_first_submitted>July 17, 2020</results_first_submitted>
  <results_first_submitted_qc>July 17, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">August 3, 2020</results_first_posted>
  <last_update_submitted>August 7, 2020</last_update_submitted>
  <last_update_submitted_qc>August 7, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">August 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Alcohol Use</keyword>
  <keyword>Pain</keyword>
  <keyword>HIV</keyword>
  <keyword>Low-dose naltrexone</keyword>
  <keyword>Nalmefene</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcohol Drinking</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Naltrexone</mesh_term>
    <mesh_term>Nalmefene</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>All data from the study will be placed into the URBAN ARCH repository.</ipd_description>
    <ipd_url>http://www.urbanarch.org</ipd_url>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 20, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/86/NCT03278886/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Low Dose Naltrexone</title>
          <description>Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.&#xD;
Low dose naltrexone: 4.5 mg of low dose naltrexone taken once daily for 8 weeks</description>
        </group>
        <group group_id="P2">
          <title>Nalmefene</title>
          <description>Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.&#xD;
Nalmefene: 18 mg of nalmefene taken once daily for 8 weeks</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Low Dose Naltrexone</title>
          <description>Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.&#xD;
Low dose naltrexone: 4.5 mg of low dose naltrexone taken once daily for 8 weeks</description>
        </group>
        <group group_id="B2">
          <title>Nalmefene</title>
          <description>Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.&#xD;
Nalmefene: 18 mg of nalmefene taken once daily for 8 weeks</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="11"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="38.3" spread="7.46"/>
                    <measurement group_id="B2" value="35.7" spread="1.09"/>
                    <measurement group_id="B3" value="37.8" spread="7.02"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race and Ethnicity Not Collected</title>
          <population>Race and Ethnicity were not collected from any participant.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="0"/>
                    <count group_id="B2" value="0"/>
                    <count group_id="B3" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Russia</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Education (9 grades or more)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Married/Living with partner/In long-term relationship</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>At risk drinking based on NIAAA criteria</title>
          <description>At risk drinking defined as &gt;14 standard drinks per week/ &gt; 4 drinks in a day for men; &gt; 7 drinks in the past week/ &gt; 3 drinks in a day for women.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Lifetime opioid use</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Past 30 day opioid use</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pain severity</title>
          <description>Scale of 1-10 with higher numbers indicating greater levels of pain</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="3.0" lower_limit="2.1" upper_limit="4.5"/>
                    <measurement group_id="B2" value="4.5" lower_limit="4.0" upper_limit="5.5"/>
                    <measurement group_id="B3" value="3.3" lower_limit="2.5" upper_limit="5.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Pain interference</title>
          <description>Scale of 1-10 with higher numbers indicating greater levels of pain</description>
          <units>units on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.5" lower_limit="2.0" upper_limit="6.7"/>
                    <measurement group_id="B2" value="5.6" lower_limit="4.1" upper_limit="7.9"/>
                    <measurement group_id="B3" value="4.1" lower_limit="2.1" upper_limit="6.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cold pain threshold</title>
          <description>Measured as number of seconds to the initial perception of pain during cold-pressor test</description>
          <units>seconds</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.5" lower_limit="7.9" upper_limit="13.5"/>
                    <measurement group_id="B2" value="10" lower_limit="3.6" upper_limit="13.5"/>
                    <measurement group_id="B3" value="10" lower_limit="6.7" upper_limit="13.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Cold pain tolerance</title>
          <description>Measured as seconds until withdrawal of hand during cold-pressor test</description>
          <units>seconds</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="8"/>
                    <count group_id="B2" value="3"/>
                    <count group_id="B3" value="11"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19.3" lower_limit="16.5" upper_limit="22.8"/>
                    <measurement group_id="B2" value="22" lower_limit="8.2" upper_limit="22.5"/>
                    <measurement group_id="B3" value="19.5" lower_limit="14" upper_limit="22.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Medication Tolerability Measured Via a 0-100 Visual Analog Scale</title>
        <description>Medication tolerability will be measured via a 0-100 visual analog scale. Participants will be asked to indicate on a scale of 0-100, how well they have tolerated the study medication with 0 anchored as &quot;cannot tolerate at all&quot; and 100 as &quot;tolerate perfectly well.&quot; Higher numbers will be indicative of higher tolerability of the medication.</description>
        <time_frame>Primary endpoint at 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Low Dose Naltrexone</title>
            <description>Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.&#xD;
Low dose naltrexone: 4.5 mg of low dose naltrexone taken once daily for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Nalmefene</title>
            <description>Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.&#xD;
Nalmefene: 18 mg of nalmefene taken once daily for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Medication Tolerability Measured Via a 0-100 Visual Analog Scale</title>
          <description>Medication tolerability will be measured via a 0-100 visual analog scale. Participants will be asked to indicate on a scale of 0-100, how well they have tolerated the study medication with 0 anchored as &quot;cannot tolerate at all&quot; and 100 as &quot;tolerate perfectly well.&quot; Higher numbers will be indicative of higher tolerability of the medication.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="90.7" spread="22.4"/>
                    <measurement group_id="O2" value="NA" spread="NA">All participants randomized to this arm discontinued study medication due to side effects. At 8-weeks, no participants in this arm were taking the study medication, so a tolerability score was not assessed.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Alcohol Use Defined as a Change in the Mean Number of Grams of Pure Ethanol Consumed Per Day From Baseline to 8 Weeks</title>
        <description>Measured via 30 Day Alcohol Use Timeline Follow Back Method</description>
        <time_frame>Baseline, 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Low Dose Naltrexone</title>
            <description>Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.&#xD;
Low dose naltrexone: 4.5 mg of low dose naltrexone taken once daily for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Nalmefene</title>
            <description>Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.&#xD;
Nalmefene: 18 mg of nalmefene taken once daily for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Alcohol Use Defined as a Change in the Mean Number of Grams of Pure Ethanol Consumed Per Day From Baseline to 8 Weeks</title>
          <description>Measured via 30 Day Alcohol Use Timeline Follow Back Method</description>
          <units>grams of ethanol</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.5" spread="10.1"/>
                    <measurement group_id="O2" value="-6.83" spread="9.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Treatment Discontinuation Defined as Patient Self-report of Stopping Medication Anytime During the Treatment Period</title>
        <description>Measured via one question asking participants if they had discontinued medication since their last visit. Assessed at 4 and 8 week study visits.</description>
        <time_frame>4 weeks, 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Low Dose Naltrexone</title>
            <description>Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.&#xD;
Low dose naltrexone: 4.5 mg of low dose naltrexone taken once daily for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Nalmefene</title>
            <description>Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.&#xD;
Nalmefene: 18 mg of nalmefene taken once daily for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Treatment Discontinuation Defined as Patient Self-report of Stopping Medication Anytime During the Treatment Period</title>
          <description>Measured via one question asking participants if they had discontinued medication since their last visit. Assessed at 4 and 8 week study visits.</description>
          <units>treatment discontinuations</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>4-Weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8-Weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Adherence to Medication Defined as Self-report of Percentage of Study Medication Taken in the Past Two Weeks</title>
        <description>Measured by participants' drawing a line on a a Visual Analog Scale, which ranges from 0 to 100. Higher numbers indicate higher adherence to study medication.</description>
        <time_frame>Endpoint at 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Low Dose Naltrexone</title>
            <description>Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.&#xD;
Low dose naltrexone: 4.5 mg of low dose naltrexone taken once daily for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Nalmefene</title>
            <description>Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.&#xD;
Nalmefene: 18 mg of nalmefene taken once daily for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Adherence to Medication Defined as Self-report of Percentage of Study Medication Taken in the Past Two Weeks</title>
          <description>Measured by participants' drawing a line on a a Visual Analog Scale, which ranges from 0 to 100. Higher numbers indicate higher adherence to study medication.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="87.5" spread="35.4"/>
                    <measurement group_id="O2" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Adherence Assessed Via Riboflavin in the Urine Confirming Adherence</title>
        <description>Measured through visual inspection of the urine for the presence or absence of riboflavin using ultraviolet (UV) light at the long wave setting (33 mm) in a room with low ambient light.</description>
        <time_frame>Endpoint at 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Low Dose Naltrexone</title>
            <description>Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.&#xD;
Low dose naltrexone: 4.5 mg of low dose naltrexone taken once daily for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Nalmefene</title>
            <description>Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.&#xD;
Nalmefene: 18 mg of nalmefene taken once daily for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Adherence Assessed Via Riboflavin in the Urine Confirming Adherence</title>
          <description>Measured through visual inspection of the urine for the presence or absence of riboflavin using ultraviolet (UV) light at the long wave setting (33 mm) in a room with low ambient light.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question</title>
        <description>Measured via a 16-item symptom checklist with the option for participants to report any experienced side effects not on the checklist. Side effect severity is rated by trained research assessors. The checklist is asked at 2, 4, 6, and 8-week study visits.</description>
        <time_frame>2 weeks, 4 weeks, 6 weeks, 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Low Dose Naltrexone</title>
            <description>Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.&#xD;
Low dose naltrexone: 4.5 mg of low dose naltrexone taken once daily for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Nalmefene</title>
            <description>Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.&#xD;
Nalmefene: 18 mg of nalmefene taken once daily for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question</title>
          <description>Measured via a 16-item symptom checklist with the option for participants to report any experienced side effects not on the checklist. Side effect severity is rated by trained research assessors. The checklist is asked at 2, 4, 6, and 8-week study visits.</description>
          <units>number of side effects</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>2-Weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.5" spread="1.6"/>
                    <measurement group_id="O2" value="4.5" spread="6.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>4-Weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.3" spread="1.2"/>
                    <measurement group_id="O2" value="1.5" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>6-Weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.9" spread="1.0"/>
                    <measurement group_id="O2" value="1.5" spread="2.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8-Weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="0"/>
                    <measurement group_id="O2" value="0" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Medication Satisfaction Defined as a Score From 0-100 Measured Via the Treatment Satisfaction Questionnaire for Medication (TSQM), With Higher Scores Corresponding to Higher Treatment Satisfaction.</title>
        <description>Measured via using the 14-item Treatment Satisfaction Questionnaire, which consists of 14 items that result in four domains: Effectiveness, Side Effects, Convenience and Global Satisfaction. Higher scores indicate greater satisfaction with medication. Assessed at 4 and 8 week study visits.</description>
        <time_frame>4 weeks, 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Low Dose Naltrexone</title>
            <description>Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.&#xD;
Low dose naltrexone: 4.5 mg of low dose naltrexone taken once daily for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Nalmefene</title>
            <description>Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.&#xD;
Nalmefene: 18 mg of nalmefene taken once daily for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Medication Satisfaction Defined as a Score From 0-100 Measured Via the Treatment Satisfaction Questionnaire for Medication (TSQM), With Higher Scores Corresponding to Higher Treatment Satisfaction.</title>
          <description>Measured via using the 14-item Treatment Satisfaction Questionnaire, which consists of 14 items that result in four domains: Effectiveness, Side Effects, Convenience and Global Satisfaction. Higher scores indicate greater satisfaction with medication. Assessed at 4 and 8 week study visits.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>4-Weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.3" spread="24.4"/>
                    <measurement group_id="O2" value="3.6" spread="5.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>8-Weeks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="47.3" spread="21.9"/>
                    <measurement group_id="O2" value="3.6" spread="5.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Severe Hepatotoxicity Defined as AST/ALT &gt;10X the Level of Normal</title>
        <description>Aminotransferase levels (AST/ALT) are tested to look for severe hepatotoxicity defined as AST/ALT &gt; 10 times the level of normal.</description>
        <time_frame>Endpoint at 8 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Low Dose Naltrexone</title>
            <description>Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.&#xD;
Low dose naltrexone: 4.5 mg of low dose naltrexone taken once daily for 8 weeks</description>
          </group>
          <group group_id="O2">
            <title>Nalmefene</title>
            <description>Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.&#xD;
Nalmefene: 18 mg of nalmefene taken once daily for 8 weeks</description>
          </group>
        </group_list>
        <measure>
          <title>Severe Hepatotoxicity Defined as AST/ALT &gt;10X the Level of Normal</title>
          <description>Aminotransferase levels (AST/ALT) are tested to look for severe hepatotoxicity defined as AST/ALT &gt; 10 times the level of normal.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected over the course of the 8-week treatment period.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Low Dose Naltrexone</title>
          <description>Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.&#xD;
Low dose naltrexone: 4.5 mg of low dose naltrexone taken once daily for 8 weeks</description>
        </group>
        <group group_id="E2">
          <title>Nalmefene</title>
          <description>Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.&#xD;
Nalmefene: 18 mg of nalmefene taken once daily for 8 weeks</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>CTCAE (5.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Body injury during fight</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_vocab>CTCAE (5.0)</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Loss of appetite</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Agitation</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Weakness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Neck pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Abnormal dreams/nightmares</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Anxiety</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Sleep problems</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Jeffrey Samet</name_or_title>
      <organization>Boston Medical Center</organization>
      <phone>617-414-7444</phone>
      <email>jsamet@bu.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03278886
org study id: H-36491
secondary id: UH2AA026193
nct id: NCT03278886
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is a randomized controlled trial (RCT) to assess the feasibility, tolerability,
      and safety of using opioid receptor antagonists (naltrexone and nalmefene) to treat pain
      among HIV-infected persons with heavy alcohol use and chronic pain.
Pain is a common co-morbidity for HIV-infected patients. Prevalence studies suggest that, on
      average, half of all HIV-infected persons suffer pain. Chronic pain can lead to heavy alcohol
      use among HIV-infected persons, which may in turn be a barrier to treatment/control of HIV
      and contribute to spread of HIV. Thus there is an urgent need to address pain among persons
      with HIV. Opioid receptor antagonists such as naltrexone and nalmefene, which are licensed
      for treatment of alcohol use disorders, show promise as being effective and safe treatments
      for chronic pain among persons with HIV. This study will pilot test novel pharmacotherapies
      (opioid receptor antagonists) to improve chronic pain among HIV-infected heavy drinkers. The
      specific aims of the research is to assess the feasibility, tolerability and safety of using
      opioid receptor antagonists (low-dose naltrexone and nalmefene) to treat pain among
      HIV-infected persons with heavy alcohol use and chronic pain.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Medication Tolerability Measured Via a 0-100 Visual Analog Scale
time frame: Primary endpoint at 8 weeks
description: Medication tolerability will be measured via a 0-100 visual analog scale. Participants will be asked to indicate on a scale of 0-100, how well they have tolerated the study medication with 0 anchored as "cannot tolerate at all" and 100 as "tolerate perfectly well." Higher numbers will be indicative of higher tolerability of the medication.
measure: Change in Alcohol Use Defined as a Change in the Mean Number of Grams of Pure Ethanol Consumed Per Day From Baseline to 8 Weeks
time frame: Baseline, 8 weeks
description: Measured via 30 Day Alcohol Use Timeline Follow Back Method
measure: Treatment Discontinuation Defined as Patient Self-report of Stopping Medication Anytime During the Treatment Period
time frame: 4 weeks, 8 weeks
description: Measured via one question asking participants if they had discontinued medication since their last visit. Assessed at 4 and 8 week study visits.
measure: Adherence to Medication Defined as Self-report of Percentage of Study Medication Taken in the Past Two Weeks
time frame: Endpoint at 8 weeks
description: Measured by participants' drawing a line on a a Visual Analog Scale, which ranges from 0 to 100. Higher numbers indicate higher adherence to study medication.
measure: Number of Participants With Adherence Assessed Via Riboflavin in the Urine Confirming Adherence
time frame: Endpoint at 8 weeks
description: Measured through visual inspection of the urine for the presence or absence of riboflavin using ultraviolet (UV) light at the long wave setting (33 mm) in a room with low ambient light.
measure: Reported Side Effects Using a Symptom Checklist, Plus an Open-ended Question
time frame: 2 weeks, 4 weeks, 6 weeks, 8 weeks
description: Measured via a 16-item symptom checklist with the option for participants to report any experienced side effects not on the checklist. Side effect severity is rated by trained research assessors. The checklist is asked at 2, 4, 6, and 8-week study visits.
measure: Medication Satisfaction Defined as a Score From 0-100 Measured Via the Treatment Satisfaction Questionnaire for Medication (TSQM), With Higher Scores Corresponding to Higher Treatment Satisfaction.
time frame: 4 weeks, 8 weeks
description: Measured via using the 14-item Treatment Satisfaction Questionnaire, which consists of 14 items that result in four domains: Effectiveness, Side Effects, Convenience and Global Satisfaction. Higher scores indicate greater satisfaction with medication. Assessed at 4 and 8 week study visits.
measure: Severe Hepatotoxicity Defined as AST/ALT >10X the Level of Normal
time frame: Endpoint at 8 weeks
description: Aminotransferase levels (AST/ALT) are tested to look for severe hepatotoxicity defined as AST/ALT > 10 times the level of normal.
arm group label: Low dose naltrexone
arm group type: Experimental
description: Participants randomized to this group will receive low dose naltrexone (4.5 mg) for 8 weeks.
arm group label: Nalmefene
arm group type: Experimental
description: Participants randomized to this group will receive nalmefene (18 mg) for 8 weeks.
intervention type: Drug
intervention name: Low dose naltrexone
description: 4.5 mg of low dose naltrexone taken once daily for 8 weeks
arm group label: Low dose naltrexone
intervention type: Drug
intervention name: Nalmefene
description: 18 mg of nalmefene taken once daily for 8 weeks
arm group label: Nalmefene
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Jeffrey H. Samet, MD, MA, MPH
role: Principal Investigator
affiliation: Boston University/Boston Medical Center
facility: 
country: Russian Federation
url: http://www.urbanarch.org
description: URBAN ARCH, a member of NIAAA CHAART (Consortiums for HIV/AIDS & Alcohol Research Translation) initiative, conducts and disseminates interdisciplinary research on how alcohol impacts people with HIV and develops interventions to reduce related outcomes.
responsible party type: Sponsor
mesh term: Alcohol Drinking
mesh term: Naltrexone
mesh term: Nalmefene
sharing ipd: Yes
ipd description: All data from the study will be placed into the URBAN ARCH repository.
ipd url: http://www.urbanarch.org
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 