<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/NCT01690546</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00036909</org_study_id>
    <nct_id>NCT01690546</nct_id>
  </id_info>
  <brief_title>Low Dose Naltrexone-buprenorphine Transfer to Vivitrol Injection in Opioid Dependence</brief_title>
  <acronym>BUP/NXT-VIVI</acronym>
  <official_title>An Open Label, Flexible Dose Study of Very Low Doses of Naltrexone-Buprenorphine Transfer to Extend-Release Naltrexone (VIVITROL®) in Opioid Addiction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Paolo Mannelli</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Alkermes, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate a very low dose naltrexone-buprenorphine treatment&#xD;
      to transfer opioid dependent individuals to extended release naltrexone injection (Vivitrol).&#xD;
      The hypothesis is that patients will complete the transfer to Vivitrol successfully, finding&#xD;
      the treatment acceptable and showing minimal withdrawal discomfort.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Thirty-five opioid dependent (OD) volunteers seeking treatment will be enrolled in an&#xD;
      open-label, flexible-dosing, outpatient trial at Duke Addictions Program. On days 1-3,&#xD;
      participants will receive buprenorphine/naloxone daily at a starting dose of 4mg,&#xD;
      progressively decreasing to 2 mg on days 2- 3. Participants will also receive very low dose&#xD;
      naltrexone (VLNTX) at a dose of 0.25 mg to 1mg on Days 1-3, 2 to 6 mg on Day 4 and between 10&#xD;
      and 50 mg on Days 5-7. Then a VIVITROL injection, 380 mg, will be administered on Day 8.&#xD;
&#xD;
      Evaluations will occur daily for up to 6 hours until 1 day after VIVITROL injection and then&#xD;
      weekly for 4 weeks. Patients will receive ancillary medications as needed and weekly&#xD;
      psychosocial intervention. At the end of the study, participants will be offered outpatient&#xD;
      treatment of OD at the study site, or will be referred to other treatment programs.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>September 2012</start_date>
  <completion_date type="Actual">February 2015</completion_date>
  <primary_completion_date type="Actual">February 2015</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Retention in Treatment</measure>
    <time_frame>4 weeks</time_frame>
    <description>After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Withdrawal Intensity as Measured by the Clinical Opiate Withdrawal Scale (COWS)</measure>
    <time_frame>4 weeks</time_frame>
    <description>After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment.&#xD;
COWS rates eleven common opiate withdrawal signs or symptoms. The summed scores ranged from 0-48, with 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Withdrawal Intensity as Measured by the Subjective Opiate Withdrawal Scale (SOWS)</measure>
    <time_frame>4 weeks</time_frame>
    <description>After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment.&#xD;
SOWS contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). Total score range is 0 - 64; the higher the score the more withdrawal symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Craving</measure>
    <time_frame>4 weeks</time_frame>
    <description>Craving, assessed with a 100-point Visual Analog Scale (VAS), ranging from 'not at all' (0) to 'more than ever' (100). The higher the score the higher the craving.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Illicit Drug Use, Measured by Urine Drug Testing</measure>
    <time_frame>4 weeks</time_frame>
    <description>number of participants that tested positive for marijuana, cocaine, and opiates.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Satisfaction With Treatment, Measured by a Treatment Satisfaction Questionnaire</measure>
    <time_frame>Day 9</time_frame>
    <description>Questionnaire consisted of 3 questions.&#xD;
Were you satisfied with the treatment (range 1-5): Completely satisfied (1) to completely dissatisfied (5).&#xD;
Were you satisfied with withdrawal treatment (range 1-5): Minimal withdrawal (1) to worse than ever (5).&#xD;
Did the medication help (range 1-5): Helped a lot (1) to No it did not help (5).&#xD;
Lower scores represent greater satisfaction.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants Who Adhered to Study Visits.</measure>
    <time_frame>baseline to end of study (approximately 40 days)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Adherence to Medication (Naltrexone)</measure>
    <time_frame>Day 1 to Day 8 (+/- 2 days)</time_frame>
    <description>Participant who took Naltrexone as prescribed.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Use of Ancillary Medications.</measure>
    <time_frame>baseline to week 1</time_frame>
    <description>Number of participants that took ancillary medication</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants That Self Reported Illicit Drug Use</measure>
    <time_frame>4 weeks</time_frame>
    <description>Participants reported on any illicit drug use to include Cocaine marijuana opiates</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">38</enrollment>
  <condition>Opiate Dependence</condition>
  <arm_group>
    <arm_group_label>BUP/VLNXT to VIVITROL</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>very low dose naltrexone</intervention_name>
    <description>On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.</description>
    <arm_group_label>BUP/VLNXT to VIVITROL</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>extended release naltrexone</intervention_name>
    <description>On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.</description>
    <arm_group_label>BUP/VLNXT to VIVITROL</arm_group_label>
    <other_name>Vivitrol</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>buprenorphine/naloxone</intervention_name>
    <description>On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.</description>
    <arm_group_label>BUP/VLNXT to VIVITROL</arm_group_label>
    <other_name>Suboxone</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men and women 18 to 65 years of age who meet DSM-IV criteria for OD of at least six&#xD;
             months duration, supported by a positive urine for opiates and a positive naloxone&#xD;
             challenge test if the diagnosis is unclear.&#xD;
&#xD;
          2. Individuals must be capable of giving informed consent and capable of complying with&#xD;
             study procedures.&#xD;
&#xD;
          3. Participants will be asked to provide locator information including the address and&#xD;
             telephone number of a non-drug abusing relative or friend who can reach the&#xD;
             participant in emergencies.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Individuals currently prescribed or regularly taking opiates for chronic pain or&#xD;
             medical illness.&#xD;
&#xD;
          2. Individuals regularly using licit or illicit methadone or BUP.&#xD;
&#xD;
          3. Individuals meeting DSM-IV criteria for schizophrenia, schizoaffective or psychotic&#xD;
             disorders, or psychiatric disorder (other than substance abuse) requiring&#xD;
             intervention.&#xD;
&#xD;
          4. Individuals who are medically unstable, or have liver enzyme function tests greater&#xD;
             than two times normal.&#xD;
&#xD;
          5. Individuals with current suicidal risk or 1 or more suicide attempts within the past&#xD;
             year.&#xD;
&#xD;
          6. History of accidental drug overdose in the last three years or any other significant&#xD;
             history of overdose following detoxification, defined as an episode of opioid-induced&#xD;
             unconsciousness or incapacitation.&#xD;
&#xD;
          7. Nursing/pregnant women, or failure in a sexually active man or woman to use adequate&#xD;
             contraceptive methods (e.g., oral or depot contraceptives, foam, sponges, and/or&#xD;
             condoms)&#xD;
&#xD;
          8. Individuals who are dependent on any other drugs (excluding nicotine)&#xD;
&#xD;
          9. Individuals with known sensitivity to BUP, VIVITROL, NTX, naloxone.&#xD;
&#xD;
         10. Individuals who are court-mandated to treatment.&#xD;
&#xD;
         11. Individuals who have a current or pending legal status, or any other condition that&#xD;
             would make them unlikely to be available for the duration of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Paolo Mannelli, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University Health Systems</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Medical Center / Civitan Building</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>April 2016</verification_date>
  <study_first_submitted>September 19, 2012</study_first_submitted>
  <study_first_submitted_qc>September 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 21, 2012</study_first_posted>
  <results_first_submitted>February 22, 2016</results_first_submitted>
  <results_first_submitted_qc>April 25, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">June 1, 2016</results_first_posted>
  <last_update_submitted>April 25, 2016</last_update_submitted>
  <last_update_submitted_qc>April 25, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">June 1, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Paolo Mannelli</investigator_full_name>
    <investigator_title>Associate Professor of Psychiatry</investigator_title>
  </responsible_party>
  <keyword>Opioid Addiction</keyword>
  <keyword>Addiction</keyword>
  <keyword>Drug Dependence</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Opioid-Related Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Naltrexone</mesh_term>
    <mesh_term>Buprenorphine</mesh_term>
    <mesh_term>Buprenorphine, Naloxone Drug Combination</mesh_term>
    <mesh_term>Naloxone</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>38 participants signed consent. 3 participants were screen failures. 35 participants started study.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>BUP/VLNXT to VIVITROL</title>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="35"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Extended Release Injectable NTX</title>
              <participants_list>
                <participants group_id="P1" count="27"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="26"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>BUP/VLNXT to VIVITROL</title>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="35"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="40.1" lower_limit="25" upper_limit="65"/>
                  </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>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Caucasian</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Years of Opioid use</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="9.7" lower_limit="7" upper_limit="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Retention in Treatment</title>
        <description>After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks.</description>
        <time_frame>4 weeks</time_frame>
        <population>All participants who received the Extended Release Injectable NTX</population>
        <group_list>
          <group group_id="O1">
            <title>BUP/VLNXT to VIVITROL</title>
          </group>
        </group_list>
        <measure>
          <title>Retention in Treatment</title>
          <description>After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks.</description>
          <population>All participants who received the Extended Release Injectable NTX</population>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Withdrawal Intensity as Measured by the Clinical Opiate Withdrawal Scale (COWS)</title>
        <description>After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment.&#xD;
COWS rates eleven common opiate withdrawal signs or symptoms. The summed scores ranged from 0-48, with 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal.</description>
        <time_frame>4 weeks</time_frame>
        <population>All participants who received the Extended Release Injectable NTX</population>
        <group_list>
          <group group_id="O1">
            <title>BUP/VLNXT to VIVITROL</title>
          </group>
        </group_list>
        <measure>
          <title>Withdrawal Intensity as Measured by the Clinical Opiate Withdrawal Scale (COWS)</title>
          <description>After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment.&#xD;
COWS rates eleven common opiate withdrawal signs or symptoms. The summed scores ranged from 0-48, with 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal.</description>
          <population>All participants who received the Extended Release Injectable NTX</population>
          <units>units 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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.64" spread="1.29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Withdrawal Intensity as Measured by the Subjective Opiate Withdrawal Scale (SOWS)</title>
        <description>After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment.&#xD;
SOWS contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). Total score range is 0 - 64; the higher the score the more withdrawal symptoms.</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BUP/VLNXT to VIVITROL</title>
          </group>
        </group_list>
        <measure>
          <title>Withdrawal Intensity as Measured by the Subjective Opiate Withdrawal Scale (SOWS)</title>
          <description>After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment.&#xD;
SOWS contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). Total score range is 0 - 64; the higher the score the more withdrawal symptoms.</description>
          <units>units 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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.52" spread="3.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Craving</title>
        <description>Craving, assessed with a 100-point Visual Analog Scale (VAS), ranging from 'not at all' (0) to 'more than ever' (100). The higher the score the higher the craving.</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BUP/VLNXT to VIVITROL</title>
          </group>
        </group_list>
        <measure>
          <title>Craving</title>
          <description>Craving, assessed with a 100-point Visual Analog Scale (VAS), ranging from 'not at all' (0) to 'more than ever' (100). The higher the score the higher the craving.</description>
          <units>units 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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.12" spread="14.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Illicit Drug Use, Measured by Urine Drug Testing</title>
        <description>number of participants that tested positive for marijuana, cocaine, and opiates.</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BUP/VLNXT to VIVITROL</title>
          </group>
        </group_list>
        <measure>
          <title>Illicit Drug Use, Measured by Urine Drug Testing</title>
          <description>number of participants that tested positive for marijuana, cocaine, and opiates.</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Marijuana</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cocaine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Opiates</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Satisfaction With Treatment, Measured by a Treatment Satisfaction Questionnaire</title>
        <description>Questionnaire consisted of 3 questions.&#xD;
Were you satisfied with the treatment (range 1-5): Completely satisfied (1) to completely dissatisfied (5).&#xD;
Were you satisfied with withdrawal treatment (range 1-5): Minimal withdrawal (1) to worse than ever (5).&#xD;
Did the medication help (range 1-5): Helped a lot (1) to No it did not help (5).&#xD;
Lower scores represent greater satisfaction.</description>
        <time_frame>Day 9</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BUP/VLNXT to VIVITROL</title>
          </group>
        </group_list>
        <measure>
          <title>Satisfaction With Treatment, Measured by a Treatment Satisfaction Questionnaire</title>
          <description>Questionnaire consisted of 3 questions.&#xD;
Were you satisfied with the treatment (range 1-5): Completely satisfied (1) to completely dissatisfied (5).&#xD;
Were you satisfied with withdrawal treatment (range 1-5): Minimal withdrawal (1) to worse than ever (5).&#xD;
Did the medication help (range 1-5): Helped a lot (1) to No it did not help (5).&#xD;
Lower scores represent greater satisfaction.</description>
          <units>units 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="27"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Were you satisfied with the treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.31" spread="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Were you satisfied with withdrawal treatment</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.04" spread="0.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Did the medication help</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.69" spread="0.93"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants Who Adhered to Study Visits.</title>
        <time_frame>baseline to end of study (approximately 40 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BUP/VLNXT to VIVITROL</title>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants Who Adhered to Study Visits.</title>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="74"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Adherence to Medication (Naltrexone)</title>
        <description>Participant who took Naltrexone as prescribed.</description>
        <time_frame>Day 1 to Day 8 (+/- 2 days)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BUP/VLNXT to VIVITROL</title>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Adherence to Medication (Naltrexone)</title>
          <description>Participant who took Naltrexone as prescribed.</description>
          <units>percentage of participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="100"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Use of Ancillary Medications.</title>
        <description>Number of participants that took ancillary medication</description>
        <time_frame>baseline to week 1</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BUP/VLNXT to VIVITROL</title>
          </group>
        </group_list>
        <measure>
          <title>Use of Ancillary Medications.</title>
          <description>Number of participants that took ancillary medication</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="35"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants That Self Reported Illicit Drug Use</title>
        <description>Participants reported on any illicit drug use to include Cocaine marijuana opiates</description>
        <time_frame>4 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>BUP/VLNXT to VIVITROL</title>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants That Self Reported Illicit Drug Use</title>
          <description>Participants reported on any illicit drug use to include Cocaine marijuana opiates</description>
          <units>participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Marijuana</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Cocaine</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Opiates</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>BUP/VLNXT to VIVITROL</title>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>persecutory ideations</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="35"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Increased Withdrawal Symptoms</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="35"/>
              </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>Paolo Mannelli, M.D</name_or_title>
      <organization>Duke University Medical Center</organization>
      <phone>919-681-0613</phone>
      <email>paolo.mannelli@dm.duke.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/NCT01690546
org study id: Pro00036909
nct id: NCT01690546
lead sponsor: 
collaborator: 
has dmc: Yes
The purpose of this study is to evaluate a very low dose naltrexone-buprenorphine treatment
      to transfer opioid dependent individuals to extended release naltrexone injection (Vivitrol).
      The hypothesis is that patients will complete the transfer to Vivitrol successfully, finding
      the treatment acceptable and showing minimal withdrawal discomfort.
Thirty-five opioid dependent (OD) volunteers seeking treatment will be enrolled in an
      open-label, flexible-dosing, outpatient trial at Duke Addictions Program. On days 1-3,
      participants will receive buprenorphine/naloxone daily at a starting dose of 4mg,
      progressively decreasing to 2 mg on days 2- 3. Participants will also receive very low dose
      naltrexone (VLNTX) at a dose of 0.25 mg to 1mg on Days 1-3, 2 to 6 mg on Day 4 and between 10
      and 50 mg on Days 5-7. Then a VIVITROL injection, 380 mg, will be administered on Day 8.

      Evaluations will occur daily for up to 6 hours until 1 day after VIVITROL injection and then
      weekly for 4 weeks. Patients will receive ancillary medications as needed and weekly
      psychosocial intervention. At the end of the study, participants will be offered outpatient
      treatment of OD at the study site, or will be referred to other treatment programs.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Retention in Treatment
time frame: 4 weeks
description: After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks.
measure: Withdrawal Intensity as Measured by the Clinical Opiate Withdrawal Scale (COWS)
time frame: 4 weeks
description: After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment.
COWS rates eleven common opiate withdrawal signs or symptoms. The summed scores ranged from 0-48, with 5-12 = mild; 13-24 = moderate; 25-36 = moderately severe; more than 36 = severe withdrawal.
measure: Withdrawal Intensity as Measured by the Subjective Opiate Withdrawal Scale (SOWS)
time frame: 4 weeks
description: After the initial titration period for opioid withdrawal (of up to 8 days), patients will receive the Vivitrol injection. Then, we will follow patients for retention out to 4 weeks and record the total time they remained in treatment.
SOWS contains 16 symptoms whose intensity the patient rates on a scale of 0 (not at all) to 4 (extremely). Total score range is 0 - 64; the higher the score the more withdrawal symptoms.
measure: Craving
time frame: 4 weeks
description: Craving, assessed with a 100-point Visual Analog Scale (VAS), ranging from 'not at all' (0) to 'more than ever' (100). The higher the score the higher the craving.
measure: Illicit Drug Use, Measured by Urine Drug Testing
time frame: 4 weeks
description: number of participants that tested positive for marijuana, cocaine, and opiates.
measure: Satisfaction With Treatment, Measured by a Treatment Satisfaction Questionnaire
time frame: Day 9
description: Questionnaire consisted of 3 questions.
Were you satisfied with the treatment (range 1-5): Completely satisfied (1) to completely dissatisfied (5).
Were you satisfied with withdrawal treatment (range 1-5): Minimal withdrawal (1) to worse than ever (5).
Did the medication help (range 1-5): Helped a lot (1) to No it did not help (5).
Lower scores represent greater satisfaction.
measure: Percentage of Participants Who Adhered to Study Visits.
time frame: baseline to end of study (approximately 40 days)
measure: Percentage of Participants With Adherence to Medication (Naltrexone)
time frame: Day 1 to Day 8 (+/- 2 days)
description: Participant who took Naltrexone as prescribed.
measure: Use of Ancillary Medications.
time frame: baseline to week 1
description: Number of participants that took ancillary medication
measure: Number of Participants That Self Reported Illicit Drug Use
time frame: 4 weeks
description: Participants reported on any illicit drug use to include Cocaine marijuana opiates
arm group label: BUP/VLNXT to VIVITROL
arm group type: Experimental
description: On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.
intervention type: Drug
intervention name: very low dose naltrexone
description: On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.
arm group label: BUP/VLNXT to VIVITROL
intervention type: Drug
intervention name: extended release naltrexone
description: On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.
arm group label: BUP/VLNXT to VIVITROL
other name: Vivitrol
intervention type: Drug
intervention name: buprenorphine/naloxone
description: On days 1-3, participants will receive buprenorphine/naloxone daily, starting at a dose of 4 mg, progressively decreasing to 2 mg on Days 2-3 and very low dose naltrexone at 0.25 mg to 1 mg on Days 1-3, 2 to 6 mg on Day 4 and 10 mg to 50 mg on Days 5-7. VIVITROL injection will be administered on Day 8 at 380 mg.
arm group label: BUP/VLNXT to VIVITROL
other name: Suboxone
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Paolo Mannelli, MD
role: Principal Investigator
affiliation: Duke University Health Systems
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Paolo Mannelli
investigator title: Associate Professor of Psychiatry
mesh term: Opioid-Related Disorders
mesh term: Naltrexone
mesh term: Buprenorphine
mesh term: Buprenorphine, Naloxone Drug Combination
mesh term: Naloxone
sharing ipd: No
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 