<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/NCT01695291</url>
  </required_header>
  <id_info>
    <org_study_id>6574</org_study_id>
    <secondary_id>R34MH095502-03</secondary_id>
    <nct_id>NCT01695291</nct_id>
  </id_info>
  <brief_title>Novel Medication Strategies Targeting Brain Mechanisms in Pediatric OCD</brief_title>
  <official_title>A Randomized, Placebo-controlled Trial of Minocycline Added to Serotonin Reuptake Inhibitors in Pediatric OCD: Examining the Effects on Clinical Symptoms and on Brain Glutamate Levels Using MRS Imaging</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>New York State Psychiatric Institute</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institute of Mental Health (NIMH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>New York State Psychiatric Institute</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will examine the feasibility and potential efficacy of augmenting SRIs with&#xD;
      minocycline. The study will assess whether the addition of minocycline leads to measurable&#xD;
      changes in striatal glutamate (Glu) levels. This study will recruit up to 45 youth ages 8-20&#xD;
      diagnosed with clinically significant OCD who have demonstrated no more than minimal response&#xD;
      to SRI treatment and are currently on a stable dose of SRI medication for at least 12 weeks.&#xD;
      Participants will be randomized to receive either 12 weeks of minocycline treatment or pill&#xD;
      placebo. Randomization will be 2:1 so that 2 of 3 participants receive minocycline. Screening&#xD;
      for eligibility will take place for 1-4 weeks. Participants will undergo magnetic resonance&#xD;
      spectroscopy (MRS) scans to measure striatal Glu levels prior to randomization, and again&#xD;
      immediately following the treatment period. During the treatment period, participants will&#xD;
      meet initially weekly and then every other week with the study psychiatrist. All participants&#xD;
      will be offered three months of open medication treatment following participation. The&#xD;
      clinical trial will only be conducted at the New York State Psychiatric Institute (NYSPI) and&#xD;
      the MRS scans may be conducted at Weill Cornell Medical Center or NYSPI.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Please see the brief summary for study description.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 2012</start_date>
  <completion_date type="Actual">May 2018</completion_date>
  <primary_completion_date type="Actual">May 2017</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Yale-Brown Obsessive Compulsive Scale, Child Version (CYBOCS)</measure>
    <time_frame>Change from Baseline at 4, 8, and 12 weeks</time_frame>
    <description>The Yale-Brown Obsessive Compulsive Scale, Child Version (CYBOCS) is a semi-structured measure of Obsessive-Compulsive Disorder (OCD) severity with excellent inter-rater reliability, internal consistency, and test-retest reliability. It is validated in those starting at age 7 and used in studies up to age 20. The CYBOCS differs from the adult YBOCS only in its use of simpler language. The total CYBOCS score ranges from 0 to 40, with higher scores indicating more severe symptomatology.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Striatal Glutamate Level Measured by Magnetic Resonance Spectroscopy (MRS).</measure>
    <time_frame>Change from Baseline at 12 weeks</time_frame>
    <description>The change in striatal glutamate level will be assessed.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">31</enrollment>
  <condition>Obsessive Compulsive Disorder</condition>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Participants randomized to placebo will receive pills that are identical in appearance to the study drug but contain no active medication.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Minocycline Augmentation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Those randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline (minimum 50 mg/day and maximum 200 mg/day). After randomization, participants will receive child proofed bottles that contain enough study medication until the next visit with an additional 3 days coverage in case of scheduling issues. All participants will have a minocycline level drawn at week 12 to confirm treatment adherence. Minocycline is FDA-approved in those ages 8 and above for treatment of infections and acne and has a favorable risk-benefit profile.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Minocycline</intervention_name>
    <description>Participants randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline. Participants will take either minocycline or pill placebo for 12 weeks.</description>
    <arm_group_label>Minocycline Augmentation</arm_group_label>
    <other_name>Minomycin, Minocin, Arestin, Aknemin, Solodyn and Dynacin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>A placebo pill will be administered twice a day (BID) for 12 weeks.</description>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Participants must be ages of 8-20 at the time of consent&#xD;
&#xD;
          -  Participants must weigh at least 25kg&#xD;
&#xD;
          -  Participants and a parent/guardian must be able to read and understand English&#xD;
&#xD;
          -  Participants must meet diagnostic criteria for obsessive-compulsive disorder with&#xD;
             score ≥ 16 on the Children's Yale-Brown Obsessive Compulsive Scale (CYBOCS)&#xD;
&#xD;
          -  Participants must be on stable dose of serotonin reuptake inhibitor (SRI) medication,&#xD;
             and must have had a minimal adequate trial of SRI medication&#xD;
&#xD;
          -  Report of at least minimal, but not full, response to current SRI medication to&#xD;
             warrant ongoing SRI treatment&#xD;
&#xD;
          -  For participants younger than 18, written informed assent by the participant and&#xD;
             consent by the parent. For participants 18 and older, written consent by the&#xD;
             participant and permission for legal guardian/parent to provide information&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Lifetime diagnosis of: psychotic disorder, bipolar disorder, eating disorder,&#xD;
             pervasive developmental disorder, mental retardation, or substance/alcohol dependence&#xD;
&#xD;
          -  Current diagnosis of major depressive disorder, Tourette's/Tic Disorder, or&#xD;
             substance/alcohol abuse&#xD;
&#xD;
          -  Positive urine screen for illicit drugs&#xD;
&#xD;
          -  Medical or psychiatric conditions that would make participation in the study unsafe&#xD;
&#xD;
          -  Active suicidal ideation&#xD;
&#xD;
          -  Females who are using hormonal birth control&#xD;
&#xD;
          -  Presence of metallic device or dental braces incompatible with MRS&#xD;
&#xD;
          -  Intelligence quotient (IQ) &lt;80&#xD;
&#xD;
          -  OCD patients with primary symptoms of hoarding (determined by CYBOCS checklist)&#xD;
&#xD;
          -  Current or past diagnosis of pediatric autoimmune neuropsychiatric disorders&#xD;
             associated with streptococcus (PANDAS)&#xD;
&#xD;
          -  Individuals who are currently receiving Exposure and Response Prevention therapy and&#xD;
             are in the acute phase of treatment.&#xD;
&#xD;
          -  Documented history of hypersensitivity or intolerance to tetracycline antibiotics&#xD;
&#xD;
          -  Use of medications that are contra-indicated with minocycline (e.g., concomitant use&#xD;
             of antacids, iron, calcium, magnesium, aluminum, zinc salts as they impair minocycline&#xD;
             absorption; of anti-coagulant drugs as minocycline has been shown to depress plasma&#xD;
             prothrombin activity; of other antibiotics or Accutane due to the rare side effect of&#xD;
             pseudotumor cerebri)&#xD;
&#xD;
          -  Inability of participant or parent/guardian to read or understand English&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>8 Years</minimum_age>
    <maximum_age>20 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Moira A Rynn, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Columbia University/NYSPI</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Weill Cornell Medical Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>New York State Psychiatric Institute</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10032</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>September 21, 2012</study_first_submitted>
  <study_first_submitted_qc>September 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 27, 2012</study_first_posted>
  <results_first_submitted>February 7, 2019</results_first_submitted>
  <results_first_submitted_qc>March 12, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">March 13, 2019</results_first_posted>
  <last_update_submitted>October 30, 2019</last_update_submitted>
  <last_update_submitted_qc>October 30, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">November 13, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>New York State Psychiatric Institute</investigator_affiliation>
    <investigator_full_name>Helen Blair Simpson</investigator_full_name>
    <investigator_title>Research Chief</investigator_title>
  </responsible_party>
  <keyword>Obsessive compulsive disorder</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Compulsive Personality Disorder</mesh_term>
    <mesh_term>Obsessive-Compulsive Disorder</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Minocycline</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 23, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT01695291/Prot_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Statistical Analysis Plan</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 7, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/91/NCT01695291/SAP_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Placebo</title>
          <description>Participants randomized to placebo will receive pills that are identical in appearance to the study drug but contain no active medication.&#xD;
Placebo: A placebo pill will be administered twice a day (BID) for 12 weeks.</description>
        </group>
        <group group_id="P2">
          <title>Minocycline Augmentation</title>
          <description>Those randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline (minimum 50 mg/day and maximum 200 mg/day). After randomization, participants will receive child proofed bottles that contain enough study medication until the next visit with an additional 3 days coverage in case of scheduling issues. All participants will have a minocycline level drawn at week 12 to confirm treatment adherence. Minocycline is FDA-approved in those ages 8 and above for treatment of infections and acne and has a favorable risk-benefit profile.&#xD;
Minocycline: Participants randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline. Participants will take either minocycline or pill placebo for 12 weeks.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="14"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="7"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Placebo</title>
          <description>Participants randomized to placebo will receive pills that are identical in appearance to the study drug but contain no active medication.&#xD;
Placebo: A placebo pill will be administered BID for 12 weeks.</description>
        </group>
        <group group_id="B2">
          <title>Minocycline Augmentation</title>
          <description>Those randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline (minimum 50 mg/day and maximum 200 mg/day). After randomization, participants will receive child proofed bottles that contain enough study medication until the next visit with an additional 3 days coverage in case of scheduling issues. All participants will have a minocycline level drawn at week 12 to confirm treatment adherence. Minocycline is FDA-approved in those ages 8 and above for treatment of infections and acne and has a favorable risk-benefit profile.&#xD;
Minocycline: Participants randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline. Participants will take either minocycline or pill placebo for 12 weeks.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
            <count group_id="B2" value="21"/>
            <count group_id="B3" value="31"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="16"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</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>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="5"/>
                    <measurement group_id="B2" value="11"/>
                    <measurement group_id="B3" value="16"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="15"/>
                  </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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="28"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                  </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="0"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="2"/>
                  </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="10"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Yale-Brown Obsessive Compulsive Scale, Child Version (CYBOCS)</title>
        <description>The Yale-Brown Obsessive Compulsive Scale, Child Version (CYBOCS) is a semi-structured measure of Obsessive-Compulsive Disorder (OCD) severity with excellent inter-rater reliability, internal consistency, and test-retest reliability. It is validated in those starting at age 7 and used in studies up to age 20. The CYBOCS differs from the adult YBOCS only in its use of simpler language. The total CYBOCS score ranges from 0 to 40, with higher scores indicating more severe symptomatology.</description>
        <time_frame>Change from Baseline at 4, 8, and 12 weeks</time_frame>
        <population>Due to the early-termination of some participants, not all completed the CYBOCS at Week 12</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants randomized to placebo will receive pills that are identical in appearance to the study drug but contain no active medication.&#xD;
Placebo: A placebo pill will be administered BID for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Minocycline Augmentation</title>
            <description>Those randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline (minimum 50 mg/day and maximum 200 mg/day). After randomization, participants will receive child proofed bottles that contain enough study medication until the next visit with an additional 3 days coverage in case of scheduling issues. All participants will have a minocycline level drawn at week 12 to confirm treatment adherence. Minocycline is FDA-approved in those ages 8 and above for treatment of infections and acne and has a favorable risk-benefit profile.&#xD;
Minocycline: Participants randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline. Participants will take either minocycline or pill placebo for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Yale-Brown Obsessive Compulsive Scale, Child Version (CYBOCS)</title>
          <description>The Yale-Brown Obsessive Compulsive Scale, Child Version (CYBOCS) is a semi-structured measure of Obsessive-Compulsive Disorder (OCD) severity with excellent inter-rater reliability, internal consistency, and test-retest reliability. It is validated in those starting at age 7 and used in studies up to age 20. The CYBOCS differs from the adult YBOCS only in its use of simpler language. The total CYBOCS score ranges from 0 to 40, with higher scores indicating more severe symptomatology.</description>
          <population>Due to the early-termination of some participants, not all completed the CYBOCS at Week 12</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="10"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="10"/>
                    <count group_id="O2" value="21"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="28.20" spread="3.79"/>
                    <measurement group_id="O2" value="29.0" spread="3.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 4</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="18"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.67" spread="4.69"/>
                    <measurement group_id="O2" value="27.11" spread="5.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 8</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25.33" spread="5.22"/>
                    <measurement group_id="O2" value="25.47" spread="5.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="26.44" spread="5.10"/>
                    <measurement group_id="O2" value="25.59" spread="6.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Striatal Glutamate Level Measured by Magnetic Resonance Spectroscopy (MRS).</title>
        <description>The change in striatal glutamate level will be assessed.</description>
        <time_frame>Change from Baseline at 12 weeks</time_frame>
        <population>Due to the early-termination of some participants, not all completed MRS at Week 12</population>
        <group_list>
          <group group_id="O1">
            <title>Placebo</title>
            <description>Participants randomized to placebo will receive pills that are identical in appearance to the study drug but contain no active medication.&#xD;
Placebo: A placebo pill will be administered BID for 12 weeks.</description>
          </group>
          <group group_id="O2">
            <title>Minocycline Augmentation</title>
            <description>Those randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline (minimum 50 mg/day and maximum 200 mg/day). After randomization, participants will receive child proofed bottles that contain enough study medication until the next visit with an additional 3 days coverage in case of scheduling issues. All participants will have a minocycline level drawn at week 12 to confirm treatment adherence. Minocycline is FDA-approved in those ages 8 and above for treatment of infections and acne and has a favorable risk-benefit profile.&#xD;
Minocycline: Participants randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline. Participants will take either minocycline or pill placebo for 12 weeks.</description>
          </group>
        </group_list>
        <measure>
          <title>Striatal Glutamate Level Measured by Magnetic Resonance Spectroscopy (MRS).</title>
          <description>The change in striatal glutamate level will be assessed.</description>
          <population>Due to the early-termination of some participants, not all completed MRS at Week 12</population>
          <units>Arbitrary Units</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="17"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="9"/>
                    <count group_id="O2" value="17"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44.49" spread="6.76"/>
                    <measurement group_id="O2" value="43.96" spread="9.18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="8"/>
                    <count group_id="O2" value="14"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="42.97" spread="8.25"/>
                    <measurement group_id="O2" value="39.35" spread="6.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Placebo</title>
          <description>Participants randomized to placebo will receive pills that are identical in appearance to the study drug but contain no active medication.&#xD;
Placebo: A placebo pill will be administered BID for 12 weeks.</description>
        </group>
        <group group_id="E2">
          <title>Minocycline Augmentation</title>
          <description>Those randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline (minimum 50 mg/day and maximum 200 mg/day). After randomization, participants will receive child proofed bottles that contain enough study medication until the next visit with an additional 3 days coverage in case of scheduling issues. All participants will have a minocycline level drawn at week 12 to confirm treatment adherence. Minocycline is FDA-approved in those ages 8 and above for treatment of infections and acne and has a favorable risk-benefit profile.&#xD;
Minocycline: Participants randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline. Participants will take either minocycline or pill placebo for 12 weeks.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Hospitalization</sub_title>
                <description>For increased hostility and threatening behaviors (N=1) and for worsening OCD symptoms (N=1)</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Worsening of OCD symptoms and an interrupted suicide attempt</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Significant esophagitis</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Drug Rash</sub_title>
                <description>Drug rash requiring prednisone treatment</description>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <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="10" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="21" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Heart racing or skipping beats</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Stomach ache or cramps</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Dry mouth</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>More thirsty</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Dizzy or light-headed</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Lost weight</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Feeling hungry</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Gained weight</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Less hungry</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Muscles weak</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Irritable or bad mood</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Angry or hostile</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Sad or low mood</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Lack of interest</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Feeling shutdown</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Mood swings</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Anxious, tense, uptight</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="6" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Lack of self-control/impulsive</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Trouble paying attention</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Racing thoughts</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Can't sit or stand still</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Tired/fatigued</sub_title>
                <counts group_id="E1" subjects_affected="5" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Sleep too much</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="8" subjects_at_risk="21"/>
              </event>
              <event>
                <sub_title>Trouble falling or staying asleep</sub_title>
                <counts group_id="E1" subjects_affected="3" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="4" subjects_at_risk="21"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Pimples or acne</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="10"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="21"/>
              </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>Kelsey Hill, Research Coordinator</name_or_title>
      <organization>New York State Psychiatric Institute</organization>
      <phone>646-774-5793</phone>
      <email>Kelsey.Hill@nyspi.columbia.edu</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01695291
org study id: 6574
secondary id: R34MH095502-03
nct id: NCT01695291
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
This study will examine the feasibility and potential efficacy of augmenting SRIs with
      minocycline. The study will assess whether the addition of minocycline leads to measurable
      changes in striatal glutamate (Glu) levels. This study will recruit up to 45 youth ages 8-20
      diagnosed with clinically significant OCD who have demonstrated no more than minimal response
      to SRI treatment and are currently on a stable dose of SRI medication for at least 12 weeks.
      Participants will be randomized to receive either 12 weeks of minocycline treatment or pill
      placebo. Randomization will be 2:1 so that 2 of 3 participants receive minocycline. Screening
      for eligibility will take place for 1-4 weeks. Participants will undergo magnetic resonance
      spectroscopy (MRS) scans to measure striatal Glu levels prior to randomization, and again
      immediately following the treatment period. During the treatment period, participants will
      meet initially weekly and then every other week with the study psychiatrist. All participants
      will be offered three months of open medication treatment following participation. The
      clinical trial will only be conducted at the New York State Psychiatric Institute (NYSPI) and
      the MRS scans may be conducted at Weill Cornell Medical Center or NYSPI.
Please see the brief summary for study description.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Yale-Brown Obsessive Compulsive Scale, Child Version (CYBOCS)
time frame: Change from Baseline at 4, 8, and 12 weeks
description: The Yale-Brown Obsessive Compulsive Scale, Child Version (CYBOCS) is a semi-structured measure of Obsessive-Compulsive Disorder (OCD) severity with excellent inter-rater reliability, internal consistency, and test-retest reliability. It is validated in those starting at age 7 and used in studies up to age 20. The CYBOCS differs from the adult YBOCS only in its use of simpler language. The total CYBOCS score ranges from 0 to 40, with higher scores indicating more severe symptomatology.
measure: Striatal Glutamate Level Measured by Magnetic Resonance Spectroscopy (MRS).
time frame: Change from Baseline at 12 weeks
description: The change in striatal glutamate level will be assessed.
arm group label: Placebo
arm group type: Placebo Comparator
description: Participants randomized to placebo will receive pills that are identical in appearance to the study drug but contain no active medication.
arm group label: Minocycline Augmentation
arm group type: Experimental
description: Those randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline (minimum 50 mg/day and maximum 200 mg/day). After randomization, participants will receive child proofed bottles that contain enough study medication until the next visit with an additional 3 days coverage in case of scheduling issues. All participants will have a minocycline level drawn at week 12 to confirm treatment adherence. Minocycline is FDA-approved in those ages 8 and above for treatment of infections and acne and has a favorable risk-benefit profile.
intervention type: Drug
intervention name: Minocycline
description: Participants randomized to minocycline will receive approximately 2 mg/kg/day, the FDA-approved dose for minocycline. Participants will take either minocycline or pill placebo for 12 weeks.
arm group label: Minocycline Augmentation
other name: Minomycin, Minocin, Arestin, Aknemin, Solodyn and Dynacin
intervention type: Other
intervention name: Placebo
description: A placebo pill will be administered twice a day (BID) for 12 weeks.
arm group label: Placebo
criteria: 
gender: All
minimum age: 8 Years
maximum age: 20 Years
healthy volunteers: No
last name: Moira A Rynn, M.D.
role: Principal Investigator
affiliation: Columbia University/NYSPI
facility: 
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: New York State Psychiatric Institute
investigator full name: Helen Blair Simpson
investigator title: Research Chief
mesh term: Compulsive Personality Disorder
mesh term: Obsessive-Compulsive Disorder
mesh term: Minocycline
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 