<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/NCT02998151</url>
  </required_header>
  <id_info>
    <org_study_id>CIN001 - {LAM}</org_study_id>
    <secondary_id>U54HD082008</secondary_id>
    <nct_id>NCT02998151</nct_id>
  </id_info>
  <brief_title>Neurophysiological and Acute Pharmacological Studies in FXS Patients</brief_title>
  <official_title>Neurophysiological and Acute Pharmacological Studies in FXS Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital Medical Center, Cincinnati</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Children's Hospital Medical Center, Cincinnati</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to utilize neurophysiologic assessments, behavioral measures and&#xD;
      clinical measures to assess how much deficits associated with Fragile X Syndrome from&#xD;
      pre-dose to post-dose using pharmacology.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>January 2016</start_date>
  <completion_date type="Actual">November 2020</completion_date>
  <primary_completion_date type="Actual">November 2020</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>This study was designed as a 4-intervention crossover, with all study participants receiving all possible interventions. These were originally placebo, acamprosate, minocycline, and lovastatin. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in EEG Relative Gamma Power</measure>
    <time_frame>Pre-dose, 4-hour post-dose</time_frame>
    <description>EEG relative gamma power at rest was calculated as the percent of power in the gamma frequencies relative to the sum of power in all frequency bands, averaged across electrodes, and calculated separately at pre-dose and post-dose timepoints. To assess the impact of drug, the pre-dose relative gamma power was subtracted from post-dose relative gamma power. Higher numbers indicate more relative gamma power post-dose; lower numbers indicate more relative gamma power pre-dose.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical Global Impressions-Improvement</measure>
    <time_frame>4-hour post-dose</time_frame>
    <description>The Clinical Global Impressions - Improvement (CGI-I) requires the clinician to assess how much the patient's illness has changed relative to pre-dose, from 1 (very much improved) to 7 (very much worse).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task</measure>
    <time_frame>4-hour post-dose</time_frame>
    <description>Woodcock Johnson Test of Cognitive Abilities III Auditory Attention subscale. Participants must identify orally presented words amid increasingly intense background noise. The scores for this subtask range from 0-50, with higher scores indicating a better outcome. Raw scores for this subscale are reported (rather than standard scores, or age- or grade-equivalents).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours Post Dose</measure>
    <time_frame>Pre-dose, 4-hour post dose</time_frame>
    <description>Four 10-item lists of unrelated words were presented orally to the examinee who was then required to immediately recall words presented, at both pre-dose and post-dose timepoints. The impact of drug was assessed by subtracting the number of words remembered post-dose from the number of words remembered pre-dose. Lower numbers indicate more words remembered post-dose; higher numbers indicate more words remembered pre-dose.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Test of Attentional Performance for Children (KiTAP) Test of Alertness</measure>
    <time_frame>Predose, 4-hour post-dose</time_frame>
    <description>Computerized task where an examinee is required to push a key when a target stimulus is presented on the screen. Scores are presented as change in median reaction time (RT), in milliseconds.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">29</enrollment>
  <condition>Fragile X Syndrome</condition>
  <arm_group>
    <arm_group_label>All Study Participants</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants received, in random order, a single dose of placebo, acamprosate, lovastatin, minocycline, or baclofen, with a two-week washout period between doses. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acamprosate</intervention_name>
    <description>two 666mg pills</description>
    <arm_group_label>All Study Participants</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Lovastatin</intervention_name>
    <description>two 20mg pills</description>
    <arm_group_label>All Study Participants</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Minocycline</intervention_name>
    <description>two 135mg pills</description>
    <arm_group_label>All Study Participants</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>placebo pill</description>
    <arm_group_label>All Study Participants</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Baclofen</intervention_name>
    <description>one 30mg pill</description>
    <arm_group_label>All Study Participants</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects ages 15-55, with fragile X syndrome (FXS) who completed the study entitled&#xD;
             &quot;Mechanisms and brain circuits underlying fragile X syndrome (IRB # 2015-8425). FXS is&#xD;
             defined as full FMR1 mutations (&gt;200 CGG repeats) confirmed by genetic testing.&#xD;
&#xD;
          -  General good health as determined by physical exam, medical history and laboratory&#xD;
             work up.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with a history of intolerance to acamprosate, lovastatin, or minocycline will&#xD;
             be excluded.&#xD;
&#xD;
          -  Subjects will also be excluded if they have taken any investigational drug within 3&#xD;
             months, have a history of substance abuse or dependence within 6 months, or&#xD;
             significant psychiatric or central nervous system neurological disease unrelated to&#xD;
             FXS.&#xD;
&#xD;
          -  Uncontrolled seizures impact EEG data as do anticonvulsants, barbiturates, lithium and&#xD;
             benzodiazepines and are exclusions (within 5 half-lives). Those taking other&#xD;
             psychiatric medications must be on stable doses for 4 weeks before any testing.&#xD;
&#xD;
          -  For female subjects of child bearing potential, a positive urine pregnancy test.&#xD;
&#xD;
          -  Potential subjects with a creatinine clearance &lt; 50 mL/min will be excluded.&#xD;
&#xD;
          -  Identified medical issues, inability to tolerate study procedures or study drug per&#xD;
             the discretion of the Principal Investigator.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>15 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Craig A Erickson, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Children's Hospital Medical Center, Cincinnati</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Cincinnati Children's Hospital Medical Center</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45229</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2021</verification_date>
  <study_first_submitted>December 1, 2016</study_first_submitted>
  <study_first_submitted_qc>December 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 20, 2016</study_first_posted>
  <results_first_submitted>June 15, 2021</results_first_submitted>
  <results_first_submitted_qc>October 27, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">November 24, 2021</results_first_posted>
  <last_update_submitted>November 23, 2021</last_update_submitted>
  <last_update_submitted_qc>November 23, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">November 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fragile X Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Minocycline</mesh_term>
    <mesh_term>Acamprosate</mesh_term>
    <mesh_term>Baclofen</mesh_term>
    <mesh_term>Lovastatin</mesh_term>
    <mesh_term>L 647318</mesh_term>
    <mesh_term>Dihydromevinolin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan: Latest study protocol with baclofen</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>August 27, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT02998151/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan: Previous study protocol with original arms</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>December 1, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT02998151/Prot_SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form: Latest consent form with baclofen</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>August 30, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT02998151/ICF_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Participants engaged in a baseline visit to gather preliminary data and ensure study compliance. Participants were then randomly assigned to different sequences for receiving acamprosate, lovastatin, minocycline, baclofen, and placebo. There was a 2-week washout period between visits.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>All Study Participants</title>
          <description>This study was designed as a 4-intervention crossover, with all study participants receiving all possible interventions. These were originally placebo, acamprosate, minocycline, and lovastatin. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this arm was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>Placebo</title>
              <participants_list>
                <participants group_id="P1" count="27">Two participants withdrew from the study before receiving placebo.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Acamprosate</title>
              <participants_list>
                <participants group_id="P1" count="16">Every participant received acamprosate prior to acamprosate's discontinuance.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Lovastatin</title>
              <participants_list>
                <participants group_id="P1" count="29">All participants received lovastatin.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Minocycline</title>
              <participants_list>
                <participants group_id="P1" count="27">Two participants withdrew from the study before receiving minocycline.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>Baclofen</title>
              <participants_list>
                <participants group_id="P1" count="18">All 13 remaining participants received baclofen after acamprosate was discontinued. Five participants were re-enrolled to receive baclofen.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="5">Acamprosate was discontinued mid-study due to undetectable serum levels and replaced with baclofen. Participants who already completed acamprosate were given the option to re-enroll and receive baclofen. Five participants received all 5 interventions; 26 received 4+ interventions.</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participant declined to re-enroll for baclofen</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Participant was not offered acamprosate; acamprosate was discontinued and replaced with baclofen</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>All Study Participants</title>
          <description>Participants received, in random order, a single dose of placebo, acamprosate, lovastatin, minocycline, or baclofen, with a two-week washout period between doses. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="29"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</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="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="24.71" spread="8.56"/>
                  </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="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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="20"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="25"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="29"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task</title>
          <description>Measure Description: Woodcock Johnson Test of Cognitive Abilities III Auditory Attention subscale. Participants must identify orally presented words amid increasingly intense background noise. The scores for this subtask range from 0-50, with higher scores indicating a better outcome. Raw scores for this subscale are reported (rather than standard scores, or age- or grade-equivalents).</description>
          <population>One participant did not complete the Woodcock Johnson.</population>
          <units>scores on a scale</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="28"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="30.89" spread="4.92"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in EEG Relative Gamma Power</title>
        <description>EEG relative gamma power at rest was calculated as the percent of power in the gamma frequencies relative to the sum of power in all frequency bands, averaged across electrodes, and calculated separately at pre-dose and post-dose timepoints. To assess the impact of drug, the pre-dose relative gamma power was subtracted from post-dose relative gamma power. Higher numbers indicate more relative gamma power post-dose; lower numbers indicate more relative gamma power pre-dose.</description>
        <time_frame>Pre-dose, 4-hour post-dose</time_frame>
        <population>Missing 1 placebo, 1 lovastatin who contributed data with excessive movement or other artifact, or were unable to complete the task.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo: placebo pill</description>
          </group>
          <group group_id="O2">
            <title>Acamprosate</title>
            <description>Acamprosate: two 666mg pills</description>
          </group>
          <group group_id="O3">
            <title>Lovastatin</title>
            <description>Lovastatin: two 20mg pills</description>
          </group>
          <group group_id="O4">
            <title>Minocycline</title>
            <description>Minocycline: two 135mg pills</description>
          </group>
          <group group_id="O5">
            <title>Baclofen</title>
            <description>Baclofen: one 30mg pill</description>
          </group>
        </group_list>
        <measure>
          <title>Change in EEG Relative Gamma Power</title>
          <description>EEG relative gamma power at rest was calculated as the percent of power in the gamma frequencies relative to the sum of power in all frequency bands, averaged across electrodes, and calculated separately at pre-dose and post-dose timepoints. To assess the impact of drug, the pre-dose relative gamma power was subtracted from post-dose relative gamma power. Higher numbers indicate more relative gamma power post-dose; lower numbers indicate more relative gamma power pre-dose.</description>
          <population>Missing 1 placebo, 1 lovastatin who contributed data with excessive movement or other artifact, or were unable to complete the task.</population>
          <units>percent of power in gamma frequencies</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="26"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="28"/>
                <count group_id="O4" value="27"/>
                <count group_id="O5" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0024" spread=".0265"/>
                    <measurement group_id="O2" value="-0.0077" spread="0.0252"/>
                    <measurement group_id="O3" value="-0.0039" spread="0.0225"/>
                    <measurement group_id="O4" value="0.0019" spread="0.0235"/>
                    <measurement group_id="O5" value="-0.0160" spread="0.0346"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Clinical Global Impressions-Improvement</title>
        <description>The Clinical Global Impressions - Improvement (CGI-I) requires the clinician to assess how much the patient's illness has changed relative to pre-dose, from 1 (very much improved) to 7 (very much worse).</description>
        <time_frame>4-hour post-dose</time_frame>
        <population>CGI-I was not collected for one participant on their minocycline day and another participant on their baclofen day.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo: placebo pill</description>
          </group>
          <group group_id="O2">
            <title>Acamprosate</title>
            <description>Acamprosate: two 666mg pills</description>
          </group>
          <group group_id="O3">
            <title>Lovastatin</title>
            <description>Lovastatin: two 20mg pills</description>
          </group>
          <group group_id="O4">
            <title>Minocycline</title>
            <description>Minocycline: two 135mg pills</description>
          </group>
          <group group_id="O5">
            <title>Baclofen</title>
            <description>Baclofen: one 30mg pill</description>
          </group>
        </group_list>
        <measure>
          <title>Clinical Global Impressions-Improvement</title>
          <description>The Clinical Global Impressions - Improvement (CGI-I) requires the clinician to assess how much the patient's illness has changed relative to pre-dose, from 1 (very much improved) to 7 (very much worse).</description>
          <population>CGI-I was not collected for one participant on their minocycline day and another participant on their baclofen day.</population>
          <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="27"/>
                <count group_id="O2" value="16"/>
                <count group_id="O3" value="29"/>
                <count group_id="O4" value="26"/>
                <count group_id="O5" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.70" spread=".61"/>
                    <measurement group_id="O2" value="3.88" spread=".62"/>
                    <measurement group_id="O3" value="3.97" spread=".50"/>
                    <measurement group_id="O4" value="3.81" spread=".49"/>
                    <measurement group_id="O5" value="3.94" spread=".43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task</title>
        <description>Woodcock Johnson Test of Cognitive Abilities III Auditory Attention subscale. Participants must identify orally presented words amid increasingly intense background noise. The scores for this subtask range from 0-50, with higher scores indicating a better outcome. Raw scores for this subscale are reported (rather than standard scores, or age- or grade-equivalents).</description>
        <time_frame>4-hour post-dose</time_frame>
        <population>Data is missing from 2 placebo, 1 acamprosate, 1 lovastatin, 2 minocycline, and 1 baclofen.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo: placebo pill</description>
          </group>
          <group group_id="O2">
            <title>Acamprosate</title>
            <description>Acamprosate: two 666mg pills</description>
          </group>
          <group group_id="O3">
            <title>Lovastatin</title>
            <description>Lovastatin: two 20mg pills</description>
          </group>
          <group group_id="O4">
            <title>Minocycline</title>
            <description>Minocycline: two 135mg pills</description>
          </group>
          <group group_id="O5">
            <title>Baclofen</title>
            <description>Baclofen: one 30mg pill</description>
          </group>
        </group_list>
        <measure>
          <title>Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task</title>
          <description>Woodcock Johnson Test of Cognitive Abilities III Auditory Attention subscale. Participants must identify orally presented words amid increasingly intense background noise. The scores for this subtask range from 0-50, with higher scores indicating a better outcome. Raw scores for this subscale are reported (rather than standard scores, or age- or grade-equivalents).</description>
          <population>Data is missing from 2 placebo, 1 acamprosate, 1 lovastatin, 2 minocycline, and 1 baclofen.</population>
          <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="25"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="28"/>
                <count group_id="O4" value="25"/>
                <count group_id="O5" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.84" spread="5.77"/>
                    <measurement group_id="O2" value="33.07" spread="5.48"/>
                    <measurement group_id="O3" value="32.93" spread="5.31"/>
                    <measurement group_id="O4" value="33.24" spread="6.04"/>
                    <measurement group_id="O5" value="33" spread="5.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours Post Dose</title>
        <description>Four 10-item lists of unrelated words were presented orally to the examinee who was then required to immediately recall words presented, at both pre-dose and post-dose timepoints. The impact of drug was assessed by subtracting the number of words remembered post-dose from the number of words remembered pre-dose. Lower numbers indicate more words remembered post-dose; higher numbers indicate more words remembered pre-dose.</description>
        <time_frame>Pre-dose, 4-hour post dose</time_frame>
        <population>One participant is missing from placebo, acamprosate, lovastatin, and minocycline conditions due to being unable to repeat list words back to experimenter (nonverbal). Baclofen and placebo are each additionally missing one participant who did not complete the pre-dose or post-dose task.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo: placebo pill</description>
          </group>
          <group group_id="O2">
            <title>Acamprosate</title>
            <description>Acamprosate: two 666mg pills</description>
          </group>
          <group group_id="O3">
            <title>Lovastatin</title>
            <description>Lovastatin: two 20mg pills</description>
          </group>
          <group group_id="O4">
            <title>Minocycline</title>
            <description>Minocycline: two 135mg pills</description>
          </group>
          <group group_id="O5">
            <title>Baclofen</title>
            <description>Baclofen: one 30mg pill</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours Post Dose</title>
          <description>Four 10-item lists of unrelated words were presented orally to the examinee who was then required to immediately recall words presented, at both pre-dose and post-dose timepoints. The impact of drug was assessed by subtracting the number of words remembered post-dose from the number of words remembered pre-dose. Lower numbers indicate more words remembered post-dose; higher numbers indicate more words remembered pre-dose.</description>
          <population>One participant is missing from placebo, acamprosate, lovastatin, and minocycline conditions due to being unable to repeat list words back to experimenter (nonverbal). Baclofen and placebo are each additionally missing one participant who did not complete the pre-dose or post-dose task.</population>
          <units>number of words remembered</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="15"/>
                <count group_id="O3" value="28"/>
                <count group_id="O4" value="26"/>
                <count group_id="O5" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-.20" spread="4.23"/>
                    <measurement group_id="O2" value="-1.47" spread="5.17"/>
                    <measurement group_id="O3" value="-1.25" spread="3.85"/>
                    <measurement group_id="O4" value="-.69" spread="5.58"/>
                    <measurement group_id="O5" value="-.88" spread="3.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Test of Attentional Performance for Children (KiTAP) Test of Alertness</title>
        <description>Computerized task where an examinee is required to push a key when a target stimulus is presented on the screen. Scores are presented as change in median reaction time (RT), in milliseconds.</description>
        <time_frame>Predose, 4-hour post-dose</time_frame>
        <population>One participant is missing from the placebo, acamprosate, lovastatin, and minocycline conditions due to being unable to participate in the task. An additional one participant each is missing from placebo, acamprosate, and lovastatin conditions due to uncollected data at either the pre-dose or post-dose timepoint.</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Placebo: placebo pill</description>
          </group>
          <group group_id="O2">
            <title>Acamprosate</title>
            <description>Acamprosate: two 666mg pills</description>
          </group>
          <group group_id="O3">
            <title>Lovastatin</title>
            <description>Lovastatin: two 20mg pills</description>
          </group>
          <group group_id="O4">
            <title>Minocycline</title>
            <description>Minocycline: two 135mg pills</description>
          </group>
          <group group_id="O5">
            <title>Baclofen</title>
            <description>Baclofen: one 30mg pill</description>
          </group>
        </group_list>
        <measure>
          <title>Test of Attentional Performance for Children (KiTAP) Test of Alertness</title>
          <description>Computerized task where an examinee is required to push a key when a target stimulus is presented on the screen. Scores are presented as change in median reaction time (RT), in milliseconds.</description>
          <population>One participant is missing from the placebo, acamprosate, lovastatin, and minocycline conditions due to being unable to participate in the task. An additional one participant each is missing from placebo, acamprosate, and lovastatin conditions due to uncollected data at either the pre-dose or post-dose timepoint.</population>
          <units>change in median RT in milliseconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="25"/>
                <count group_id="O2" value="14"/>
                <count group_id="O3" value="27"/>
                <count group_id="O4" value="26"/>
                <count group_id="O5" value="18"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.76" spread="188.37"/>
                    <measurement group_id="O2" value="-28.64" spread="137.21"/>
                    <measurement group_id="O3" value="18.59" spread="169.39"/>
                    <measurement group_id="O4" value="26.85" spread="226.69"/>
                    <measurement group_id="O5" value="-31.44" spread="171.91"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse events were collected up to four weeks after the final dosing visit.</time_frame>
      <desc>Participants were asked about adverse events in person 4 hours after each dose and at the end of each dosing visit, and via phone calls conducted one day after and 8 days after each dosing visit. Additionally, participants were contacted by phone 4 weeks after the final dosing visit.</desc>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Placebo: placebo pill</description>
        </group>
        <group group_id="E2">
          <title>Acamprosate</title>
          <description>Acamprosate: two 666mg pills</description>
        </group>
        <group group_id="E3">
          <title>Lovastatin</title>
          <description>Lovastatin: two 20mg pills</description>
        </group>
        <group group_id="E4">
          <title>Minocycline</title>
          <description>Minocycline: two 135mg pills</description>
        </group>
        <group group_id="E5">
          <title>Baclofen</title>
          <description>Baclofen: one 30mg pill</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="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E5" 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="27"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E5" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>CTCAE v5.0</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="27"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="16"/>
                <counts group_id="E3" subjects_affected="4" subjects_at_risk="29"/>
                <counts group_id="E4" subjects_affected="4" subjects_at_risk="27"/>
                <counts group_id="E5" subjects_affected="4" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Blurred vision</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="18"/>
              </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="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Stomach pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="3" subjects_affected="3" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="3" subjects_affected="3" subjects_at_risk="27"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Somnolence</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Irritability</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E5" events="2" subjects_affected="2" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Confusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Mania</sub_title>
                <description>excessive talking or hyperactivity</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Allergic rhinitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="18"/>
              </event>
              <event>
                <sub_title>Sore throat</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="18"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Rash maculo-papular</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="16"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="29"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="27"/>
                <counts group_id="E5" events="1" subjects_affected="1" 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>
    <point_of_contact>
      <name_or_title>Dr. Craig Erickson</name_or_title>
      <organization>Cincinnati Children's Hospital Medical Center</organization>
      <phone>513-636-0523</phone>
      <email>craig.erickson@cchmc.org</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/NCT02998151
org study id: CIN001 - {LAM}
secondary id: U54HD082008
nct id: NCT02998151
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated device: No
The aim of this study is to utilize neurophysiologic assessments, behavioral measures and
      clinical measures to assess how much deficits associated with Fragile X Syndrome from
      pre-dose to post-dose using pharmacology.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This study was designed as a 4-intervention crossover, with all study participants receiving all possible interventions. These were originally placebo, acamprosate, minocycline, and lovastatin. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed.
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in EEG Relative Gamma Power
time frame: Pre-dose, 4-hour post-dose
description: EEG relative gamma power at rest was calculated as the percent of power in the gamma frequencies relative to the sum of power in all frequency bands, averaged across electrodes, and calculated separately at pre-dose and post-dose timepoints. To assess the impact of drug, the pre-dose relative gamma power was subtracted from post-dose relative gamma power. Higher numbers indicate more relative gamma power post-dose; lower numbers indicate more relative gamma power pre-dose.
measure: Clinical Global Impressions-Improvement
time frame: 4-hour post-dose
description: The Clinical Global Impressions - Improvement (CGI-I) requires the clinician to assess how much the patient's illness has changed relative to pre-dose, from 1 (very much improved) to 7 (very much worse).
measure: Woodcock Johnson Test of Cognitive Abilities - Auditory Attention Task
time frame: 4-hour post-dose
description: Woodcock Johnson Test of Cognitive Abilities III Auditory Attention subscale. Participants must identify orally presented words amid increasingly intense background noise. The scores for this subtask range from 0-50, with higher scores indicating a better outcome. Raw scores for this subscale are reported (rather than standard scores, or age- or grade-equivalents).
measure: Change From Pre-dose in the Repeatable Battery for the Assessment of Neuropsychological Status at 4 Hours Post Dose
time frame: Pre-dose, 4-hour post dose
description: Four 10-item lists of unrelated words were presented orally to the examinee who was then required to immediately recall words presented, at both pre-dose and post-dose timepoints. The impact of drug was assessed by subtracting the number of words remembered post-dose from the number of words remembered pre-dose. Lower numbers indicate more words remembered post-dose; higher numbers indicate more words remembered pre-dose.
measure: Test of Attentional Performance for Children (KiTAP) Test of Alertness
time frame: Predose, 4-hour post-dose
description: Computerized task where an examinee is required to push a key when a target stimulus is presented on the screen. Scores are presented as change in median reaction time (RT), in milliseconds.
arm group label: All Study Participants
arm group type: Experimental
description: Participants received, in random order, a single dose of placebo, acamprosate, lovastatin, minocycline, or baclofen, with a two-week washout period between doses. Midway through the study (n=16) it was determined that acamprosate was undetectable in serum and this intervention was replaced by baclofen. Remaining participants (n=13) received baclofen and 5 participants were re-enrolled to receive baclofen or a second round of placebo, so investigators and participants would remain blinded to drug status during the baclofen visit. The second round of placebo was not analyzed.
intervention type: Drug
intervention name: Acamprosate
description: two 666mg pills
arm group label: All Study Participants
intervention type: Drug
intervention name: Lovastatin
description: two 20mg pills
arm group label: All Study Participants
intervention type: Drug
intervention name: Minocycline
description: two 135mg pills
arm group label: All Study Participants
intervention type: Drug
intervention name: Placebo
description: placebo pill
arm group label: All Study Participants
intervention type: Drug
intervention name: Baclofen
description: one 30mg pill
arm group label: All Study Participants
criteria: 
gender: All
minimum age: 15 Years
maximum age: 55 Years
healthy volunteers: No
last name: Craig A Erickson, M.D.
role: Principal Investigator
affiliation: Children's Hospital Medical Center, Cincinnati
facility: 
country: United States
responsible party type: Sponsor
mesh term: Fragile X Syndrome
mesh term: Minocycline
mesh term: Acamprosate
mesh term: Baclofen
mesh term: Lovastatin
mesh term: L 647318
mesh term: Dihydromevinolin
provided document: 
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 