<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/NCT03018704</url>
  </required_header>
  <id_info>
    <org_study_id>NURA-010-16S</org_study_id>
    <nct_id>NCT03018704</nct_id>
  </id_info>
  <brief_title>Topiramate Treatment of Alcohol Use Disorders in African Americans</brief_title>
  <official_title>Topiramate Treatment of Alcohol Use Disorder in African Americans</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Office of Research and Development</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>VA Office of Research and Development</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The focus of this application is on the improvement of services for African American (AAs)&#xD;
      Veterans afflicted with an alcohol use disorder. The project focuses on the use of topiramate&#xD;
      as a treatment for alcohol use disorders. Despite having lower rates of heavy drinking than&#xD;
      European Americans (EAs), AAs have significantly higher rates of mortality from a variety of&#xD;
      alcohol-related conditions, including liver cirrhosis, accidents, and violence. Despite the&#xD;
      higher rates of morbidity and mortality, pharmacological treatments are understudied in this&#xD;
      population and there is some evidence that medications are less preferred and less effective&#xD;
      in AAs.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Objective(s): Despite having lower rates of drinking and heavy drinking than European&#xD;
           Americans (EAs), African Americans (AA) have significantly higher rates of mortality&#xD;
           from a variety of alcohol-related conditions, including liver cirrhosis, accidents, and&#xD;
           violence. The current proposal aims to improve alcohol treatment in AA Veterans, who&#xD;
           comprise 12% of the Veteran population.&#xD;
&#xD;
        2. Research Design: The proposed study is a two-arm, randomized 12-week, parallel-groups&#xD;
           comparison of topiramate versus placebo to reduce the frequency of heavy drinking days&#xD;
           and increase the number of abstinent days in 160 AA patients with AUD.&#xD;
&#xD;
        3. Methodology: The following specific aim is used to direct the methods:&#xD;
&#xD;
           Specific Aim 1. Understanding health disparities. Aim 1 will focus on the screening&#xD;
           process, using the screening outcomes data, including reasons for patients declining to&#xD;
           participate in the trial, to conduct descriptive analyses of the screening process and&#xD;
           recruitment efforts. We will supplement this description by examining changes in&#xD;
           drinking and motivation for treatment before and during the pandemic. In the resultant&#xD;
           manuscript, we will also discuss strategies for recruiting a minority population to&#xD;
           participate in addiction treatment studies.&#xD;
&#xD;
           Specific Aim 2. Future study planning with safety results. Aim 2 will focus on assessing&#xD;
           the safety and tolerability of topiramate dosing, which will provide the basis for&#xD;
           evaluating the risks associated with topiramate treatment for reducing heavy drinking in&#xD;
           AAs. The additional participants will greatly improve our effect size estimate, pooling&#xD;
           across sites; for example, the width of a confidence interval on a difference in means&#xD;
           at the end of the study based on a sample of size 80 will be 61% of the width of a&#xD;
           corresponding confidence interval based on a sample of size 30. In addition, two sites&#xD;
           will also provide information on treatment-by-site heterogeneity, which will be useful&#xD;
           for informing the design of a multi-site trial, which we believe is the best option for&#xD;
           recruiting an adequate sample for a well powered efficacy trial. To increase the number&#xD;
           of subjects exposed to topiramate treatment, we will randomize participants to a 2:1&#xD;
           ratio of topiramate to placebo treatment.&#xD;
&#xD;
           Specific Aim 3. Combined analysis with available RCT datasets. We have data available&#xD;
           from two completed RCTs of topiramate that used a design almost identical to that of the&#xD;
           present study (n's = 138 and 170, including 16 AAs). We plan to conduct an analysis that&#xD;
           combines the data from the three trials, to test for differences in efficacy by&#xD;
           population group (i.e., AAs and EAs), and to compare adverse event profiles across&#xD;
           population groups. Combining the datasets will allow analyses that incorporate&#xD;
           individual-level heterogeneity, in contrast to meta-analyses, where typically only group&#xD;
           comparisons would be possible. This will be accomplished using de-identified data from&#xD;
           each study.&#xD;
&#xD;
        4. Impact/Significance: The proposal is innovative in that it will focus on AAs with AUD,&#xD;
           an understudied and underserved population for whom no such data currently exist. Given&#xD;
           the far-reaching effects of AUD and its high prevalence among Veterans, added evidence&#xD;
           based treatments may realize reduced health care costs from unnecessary ED visits and&#xD;
           reduced complications of illnesses such as hepatitis C and congestive heart failure.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    In ability to recruit&#xD;
  </why_stopped>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Percent Days of Heavy Drinking</measure>
    <time_frame>12 weeks</time_frame>
    <description>Drinking was recorded using the timeline follow back methodology which is an interview based method to record drinking on each day during the trial. The summary measure (% days heavy drinking) counts the number of days of heavy drinking (&gt;4drinks per day) divided by the number of observation days to report the percent of observation days for which there is heavy drinking. For the the outcome measure the observation period is the last 42 days of the trial.</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">79</enrollment>
  <condition>Alcohol Use Disorder</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>a placebo control arm</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Topiramate</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Topiramate an FDA approved anticonvulsant has been shown effective in the treatment of alcohol use disorder but there is no data supporting use in minority patients. The medication was dosed orally twice per day with a starting dose of 25 mg, increasing the dose as tolerated to 200mg daily in divided doses. Patient were titrated to the highest dose tolerable.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Topiramate</intervention_name>
    <description>anticonvulsant medication. The medication was dosed twice per day with a starting dose of 25 mg, increasing the dose as tolerated to 200mg daily in divided doses. Patient were titrated to the highest dose tolerable.</description>
    <arm_group_label>Topiramate</arm_group_label>
    <other_name>Topamax</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>placebo</intervention_name>
    <description>inactive medication. the doses of placebo were titrated the same as the active intervention.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. self-identification as African American;&#xD;
&#xD;
          2. age 18 to 70 years, inclusive;&#xD;
&#xD;
          3. average weekly ethanol consumption of &gt;24 standard drinks for men or &gt;18 standard&#xD;
             drinks for women, with a weekly average of &gt; 2 heavy drinking days (men: &gt; 5 standard&#xD;
             drinks; women: &gt; 4 standard drinks) during the month before screening;&#xD;
&#xD;
          4. a current diagnosis of moderate or severe AUD (i.e., meeting at least 4 of 11 DSM-5&#xD;
             AUD criteria);&#xD;
&#xD;
          5. expressed goal to reduce or stop drinking;&#xD;
&#xD;
          6. able to read English at the 6th grade or higher level and without gross cognitive&#xD;
             impairment;&#xD;
&#xD;
          7. women of child-bearing potential (i.e., who have not had a hysterectomy, bilateral&#xD;
             oophorectomy, tubal ligation or are less than two years postmenopausal), must be&#xD;
             non-lactating, practicing a reliable method of birth control, and have a negative&#xD;
             urine pregnancy test prior to initiation of treatment&#xD;
&#xD;
          8. willing and able to provide signed, informed consent to participate in the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. a current, clinically significant physical disease or abnormality on the basis of&#xD;
             medical history, physical examination, or routine laboratory evaluation, including&#xD;
             direct bilirubin elevations of &gt;110% or a transaminase elevation &gt;300% of normal;&#xD;
&#xD;
          2. history of nephrolithiasis;&#xD;
&#xD;
          3. history of glaucoma;&#xD;
&#xD;
          4. current serious psychiatric illness (i.e., schizophrenia, bipolar disorder, severe or&#xD;
             psychotic major depression, antisocial personality disorder, or imminent suicide or&#xD;
             violence risk);&#xD;
&#xD;
          5. current moderate-to-severe alcohol withdrawal requiring pharmacological treatment (see&#xD;
             Section D.4.a. regarding alcohol detoxification);&#xD;
&#xD;
          6. current DSM-IV diagnosis of drug use disorder (other than nicotine or cannabis) or a&#xD;
             urine drug screen positive for recent use of opioids, cocaine, or amphetamines (may be&#xD;
             repeated once and if the result is negative on repeat it is not exclusionary);&#xD;
&#xD;
          7. a history of hypersensitivity to TOP;&#xD;
&#xD;
          8. current regular treatment with more than one antidepressant or any treatment with a&#xD;
             tricyclic antidepressant;&#xD;
&#xD;
          9. current treatment with a psychotropic medication (with the exception of&#xD;
             antidepressants where monotherapy is allowable), including medications that, when&#xD;
             combined with alcohol or TOP, present a risk of overdose or significant adverse effect&#xD;
             (e.g., chronic opioid use) (of note we will allow subjects to discontinue medications&#xD;
             that have no demonstrated therapeutic effect in order to enroll - amount of time off&#xD;
             of the medication will be a clinical decision left to the discretion of the study&#xD;
             physician investigators);&#xD;
&#xD;
         10. current treatment with TOP or a medication approved for AUD;&#xD;
&#xD;
         11. considered to be unsuitable candidates for receipt of an investigational drug;&#xD;
&#xD;
         12. treatment with carbonic anhydrase inhibitors, due to the added risk of metabolic&#xD;
             acidosis,&#xD;
&#xD;
         13. Body Mass Index (BMI) of less than 18.5.&#xD;
&#xD;
         14. untreated gout as topiramate has been shown in one study to increase uric acid.&#xD;
&#xD;
         15. current treatment with dolutegravir.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>David W. Oslin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Atlanta VA Medical and Rehab Center, Decatur, GA</name>
      <address>
        <city>Decatur</city>
        <state>Georgia</state>
        <zip>30033</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA</name>
      <address>
        <city>Philadelphia</city>
        <state>Pennsylvania</state>
        <zip>19104</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>January 10, 2017</study_first_submitted>
  <study_first_submitted_qc>January 11, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 12, 2017</study_first_posted>
  <results_first_submitted>December 15, 2022</results_first_submitted>
  <results_first_submitted_qc>March 21, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 23, 2023</results_first_posted>
  <last_update_submitted>March 21, 2023</last_update_submitted>
  <last_update_submitted_qc>March 21, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>alcoholism</keyword>
  <keyword>treatment</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Alcoholism</mesh_term>
    <mesh_term>Alcohol Drinking</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Topiramate</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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>March 3, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT03018704/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>April 21, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT03018704/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Subjects were recruited from VA outpatient and inpatient mental health and addiction programs. Recruitment occurred between October 2017 through May 2020</recruitment_details>
      <pre_assignment_details>Prior to randomization, consented individuals (n=79) were assessed for participation. The majority of non randomized subjects (n=31) didn't meet inclusion criteria (not drinking) or exclusion criteria (other drugs). I addition 5 subjects withdrew consent before randomization and 6 were lost to follow up. That lead to 37 who were randomized.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>a placebo control arm&#xD;
placebo: inactive medication</description>
        </group>
        <group group_id="P2">
          <title>Topiramate</title>
          <description>Topiramate an FDA approved anticonvulsant has been shown effective in the treatment of alcohol use disorder but there is no data supporting use in minority patients.&#xD;
Topiramate: anticonvulsant medication</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="19"/>
                <participants group_id="P2" count="18"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="18"/>
                <participants group_id="P2" count="17"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>a placebo control arm&#xD;
placebo: inactive medication</description>
        </group>
        <group group_id="B2">
          <title>Topiramate</title>
          <description>Topiramate an FDA approved anticonvulsant has been shown effective in the treatment of alcohol use disorder but there is no data supporting use in minority patients.&#xD;
Topiramate: anticonvulsant medication</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="19"/>
            <count group_id="B2" value="18"/>
            <count group_id="B3" value="37"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="50.5" spread="10.2"/>
                    <measurement group_id="B2" value="48" spread="11.6"/>
                    <measurement group_id="B3" value="49.3" spread="10.8"/>
                  </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="1"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <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>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <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>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="18"/>
                    <measurement group_id="B3" value="37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Percent Heavy Drinking days</title>
          <description>Drinking was recorded using the timeline follow back methodology which is an interview based method to record drinking on each day. The summary measure counts the number of days of heavy drinking (&gt;4drinks per day) divided by the number of observation days to report the percent of observation days for which there is heavy drinking. For the prestudy period, the observation period is 90 days.</description>
          <units>percent of trial days of heavy drinking</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70.8" spread="20.4"/>
                    <measurement group_id="B2" value="62.8" spread="23.4"/>
                    <measurement group_id="B3" value="67" spread="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Depression rating (PHQ9)</title>
          <description>Depression scale range 0-27 higher indicates more depression</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8.6" spread="7.6"/>
                    <measurement group_id="B2" value="11.4" spread="7.0"/>
                    <measurement group_id="B3" value="10." spread="7.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Percent Days of Heavy Drinking</title>
        <description>Drinking was recorded using the timeline follow back methodology which is an interview based method to record drinking on each day during the trial. The summary measure (% days heavy drinking) counts the number of days of heavy drinking (&gt;4drinks per day) divided by the number of observation days to report the percent of observation days for which there is heavy drinking. For the the outcome measure the observation period is the last 42 days of the trial.</description>
        <time_frame>12 weeks</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>a placebo control arm&#xD;
placebo: inactive medication</description>
          </group>
          <group group_id="O2">
            <title>Topiramate</title>
            <description>Topiramate an FDA approved anticonvulsant has been shown effective in the treatment of alcohol use disorder but there is no data supporting use in minority patients.&#xD;
Topiramate: anticonvulsant medication</description>
          </group>
        </group_list>
        <measure>
          <title>Percent Days of Heavy Drinking</title>
          <description>Drinking was recorded using the timeline follow back methodology which is an interview based method to record drinking on each day during the trial. The summary measure (% days heavy drinking) counts the number of days of heavy drinking (&gt;4drinks per day) divided by the number of observation days to report the percent of observation days for which there is heavy drinking. For the the outcome measure the observation period is the last 42 days of the trial.</description>
          <units>percentage of days of heavy drinking</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="18"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.7" spread="24.9"/>
                    <measurement group_id="O2" value="14.8" spread="14.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events are measured at each study visit during the trial and reported as a summary of events over the 12 weeks.</time_frame>
      <desc>No difference</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>a placebo control arm&#xD;
placebo: inactive medication</description>
        </group>
        <group group_id="E2">
          <title>Topiramate</title>
          <description>Topiramate an FDA approved anticonvulsant has been shown effective in the treatment of alcohol use disorder but there is no data supporting use in minority patients.&#xD;
Topiramate: anticonvulsant medication</description>
        </group>
      </group_list>
      <serious_events>
        <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="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </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="0" subjects_at_risk="19"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="18"/>
              </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>
    <limitations_and_caveats>The study was stopped by the funding agency due to difficulty recruiting during COVID pandemic</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>David Oslin</name_or_title>
      <organization>Department of Veteran Affairs</organization>
      <phone>215-823-5894</phone>
      <email>dave.oslin@va.gov</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/NCT03018704
org study id: NURA-010-16S
nct id: NCT03018704
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
The focus of this application is on the improvement of services for African American (AAs)
      Veterans afflicted with an alcohol use disorder. The project focuses on the use of topiramate
      as a treatment for alcohol use disorders. Despite having lower rates of heavy drinking than
      European Americans (EAs), AAs have significantly higher rates of mortality from a variety of
      alcohol-related conditions, including liver cirrhosis, accidents, and violence. Despite the
      higher rates of morbidity and mortality, pharmacological treatments are understudied in this
      population and there is some evidence that medications are less preferred and less effective
      in AAs.
1. Objective(s): Despite having lower rates of drinking and heavy drinking than European
           Americans (EAs), African Americans (AA) have significantly higher rates of mortality
           from a variety of alcohol-related conditions, including liver cirrhosis, accidents, and
           violence. The current proposal aims to improve alcohol treatment in AA Veterans, who
           comprise 12% of the Veteran population.

        2. Research Design: The proposed study is a two-arm, randomized 12-week, parallel-groups
           comparison of topiramate versus placebo to reduce the frequency of heavy drinking days
           and increase the number of abstinent days in 160 AA patients with AUD.

        3. Methodology: The following specific aim is used to direct the methods:

           Specific Aim 1. Understanding health disparities. Aim 1 will focus on the screening
           process, using the screening outcomes data, including reasons for patients declining to
           participate in the trial, to conduct descriptive analyses of the screening process and
           recruitment efforts. We will supplement this description by examining changes in
           drinking and motivation for treatment before and during the pandemic. In the resultant
           manuscript, we will also discuss strategies for recruiting a minority population to
           participate in addiction treatment studies.

           Specific Aim 2. Future study planning with safety results. Aim 2 will focus on assessing
           the safety and tolerability of topiramate dosing, which will provide the basis for
           evaluating the risks associated with topiramate treatment for reducing heavy drinking in
           AAs. The additional participants will greatly improve our effect size estimate, pooling
           across sites; for example, the width of a confidence interval on a difference in means
           at the end of the study based on a sample of size 80 will be 61% of the width of a
           corresponding confidence interval based on a sample of size 30. In addition, two sites
           will also provide information on treatment-by-site heterogeneity, which will be useful
           for informing the design of a multi-site trial, which we believe is the best option for
           recruiting an adequate sample for a well powered efficacy trial. To increase the number
           of subjects exposed to topiramate treatment, we will randomize participants to a 2:1
           ratio of topiramate to placebo treatment.

           Specific Aim 3. Combined analysis with available RCT datasets. We have data available
           from two completed RCTs of topiramate that used a design almost identical to that of the
           present study (n's = 138 and 170, including 16 AAs). We plan to conduct an analysis that
           combines the data from the three trials, to test for differences in efficacy by
           population group (i.e., AAs and EAs), and to compare adverse event profiles across
           population groups. Combining the datasets will allow analyses that incorporate
           individual-level heterogeneity, in contrast to meta-analyses, where typically only group
           comparisons would be possible. This will be accomplished using de-identified data from
           each study.

        4. Impact/Significance: The proposal is innovative in that it will focus on AAs with AUD,
           an understudied and underserved population for whom no such data currently exist. Given
           the far-reaching effects of AUD and its high prevalence among Veterans, added evidence
           based treatments may realize reduced health care costs from unnecessary ED visits and
           reduced complications of illnesses such as hepatitis C and congestive heart failure.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Percent Days of Heavy Drinking
time frame: 12 weeks
description: Drinking was recorded using the timeline follow back methodology which is an interview based method to record drinking on each day during the trial. The summary measure (% days heavy drinking) counts the number of days of heavy drinking (>4drinks per day) divided by the number of observation days to report the percent of observation days for which there is heavy drinking. For the the outcome measure the observation period is the last 42 days of the trial.
arm group label: Placebo
arm group type: Placebo Comparator
description: a placebo control arm
arm group label: Topiramate
arm group type: Experimental
description: Topiramate an FDA approved anticonvulsant has been shown effective in the treatment of alcohol use disorder but there is no data supporting use in minority patients. The medication was dosed orally twice per day with a starting dose of 25 mg, increasing the dose as tolerated to 200mg daily in divided doses. Patient were titrated to the highest dose tolerable.
intervention type: Drug
intervention name: Topiramate
description: anticonvulsant medication. The medication was dosed twice per day with a starting dose of 25 mg, increasing the dose as tolerated to 200mg daily in divided doses. Patient were titrated to the highest dose tolerable.
arm group label: Topiramate
other name: Topamax
intervention type: Drug
intervention name: placebo
description: inactive medication. the doses of placebo were titrated the same as the active intervention.
arm group label: Placebo
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: David W. Oslin, MD
role: Principal Investigator
affiliation: Corporal Michael J. Crescenz VA Medical Center, Philadelphia, PA
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Alcoholism
mesh term: Alcohol Drinking
mesh term: Topiramate
sharing ipd: No
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: The study was stopped by the funding agency due to difficulty recruiting during COVID pandemic
point of contact: 