<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/NCT02234752</url>
  </required_header>
  <id_info>
    <org_study_id>SPHS IRB # 604148-4</org_study_id>
    <nct_id>NCT02234752</nct_id>
  </id_info>
  <brief_title>Galantamine and Memantine Combination for Cognitive Impairments in Schizophrenia</brief_title>
  <official_title>A Proof-of Concept Trial of Galantamine and Memantine for Cognitive Impairments in Schizophrenia: Is the Combination Effective?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Sheppard Pratt Health System</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Sheppard Pratt Health System</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Aim: To examine the efficacy of the combination of galantamine and memantine for the&#xD;
      treatment of cognitive deficits in outpatients with schizophrenia.&#xD;
&#xD;
      Hypothesis: A combination of galantamine and memantine will improve cognitive impairments in&#xD;
      patients with schizophrenia.&#xD;
&#xD;
      This is an open-label study to evaluate whether a six week course of galantamine ER and&#xD;
      memantine XR is effective in improving the cognitive performance of patients with&#xD;
      schizophrenia or schizoaffective disorder. The primary outcome measure will be the change in&#xD;
      level of cognition as measured by the MATRICS Consensus Cognitive Battery (MCCB). The results&#xD;
      of the MATRICS collaborative project recommended the need for standardized cognitive tests&#xD;
      that better distinguish the different facets of cognitive dysfunction in schizophrenia. The&#xD;
      MCCB will assess the following seven domains: attention/vigilance, reasoning and problem&#xD;
      solving, processing speed, social cognition, verbal learning and memory, visual learning and&#xD;
      memory, and working memory. The MCCB will be administered at baseline and at the end of the&#xD;
      study. We will report total score and each domain score in the MCCB at baseline and six&#xD;
      weeks.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Funding no longer available and PI no longer working at the institution&#xD;
  </why_stopped>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">July 2016</completion_date>
  <primary_completion_date type="Actual">July 2016</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Level of Cognition</measure>
    <time_frame>Baseline and 6-Weeks</time_frame>
    <description>The primary outcome measure will be the change in level of cognition as measured by the MATRICS Consensus Cognitive Battery (MCCB). In schizophrenia, usual composite scores are 20-39. In healthy controls, usual composite scores are normalized to 40-60. Higher values of composite scores mean better cognition. Test scores are normalized to healthy controls, therefore no min-max range is available. Final scores calculated by MATRICS Consensus Cognitive Battery software. Exact minimum/maximum are not known to provider. Overall composite scores are reported.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Free Tryptophan (TRP)</measure>
    <time_frame>Baseline and 6-Weeks</time_frame>
    <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kynurenic Acid (KYNA)</measure>
    <time_frame>Baseline and 6-Weeks</time_frame>
    <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. MS* AUC is mass spectrometry times area under the curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Kynurenine (KYN)</measure>
    <time_frame>Baseline and 6-Weeks</time_frame>
    <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Picolinic Acid (PIC)</measure>
    <time_frame>Baseline and 6-Weeks</time_frame>
    <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. MS* AUC is mass spectrometry times area under the curve.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>KYN/TRP</measure>
    <time_frame>Baseline and 6-Weeks</time_frame>
    <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>KYNA/KYN</measure>
    <time_frame>Baseline and 6-Weeks</time_frame>
    <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PIC/KYN</measure>
    <time_frame>Baseline and 6-Weeks</time_frame>
    <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">3</enrollment>
  <condition>Schizophrenia</condition>
  <condition>Schizoaffective Disorder</condition>
  <arm_group>
    <arm_group_label>Galantamine ER, Memantine XR</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Week 1, Galantamine ER 8 mg HS &amp; Memantine XR 7 mg HS Week 2, Galantamine ER 16 mg HS &amp; Memantine XR 14 mg HS Weeks 3-6, Galantamine ER 24 mg HS &amp; Memantine XR 21 mg HS</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Galantamine ER</intervention_name>
    <arm_group_label>Galantamine ER, Memantine XR</arm_group_label>
    <other_name>Razadyne</other_name>
    <other_name>Razadyne ER</other_name>
    <other_name>Formerly known as Reminyl</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Memantine XR</intervention_name>
    <arm_group_label>Galantamine ER, Memantine XR</arm_group_label>
    <other_name>Namenda</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Be male or female aged 18 to 55 years (inclusive).&#xD;
&#xD;
          -  Have a DSM-5 diagnosis of schizophrenia or schizoaffective disorder confirmed by&#xD;
             medical records. Duration of illness must be ≥ 1year.&#xD;
&#xD;
          -  Be clinically stable for at least two months (i.e., has no more than a &quot;moderately&#xD;
             severe&quot; severity rating on the following BPRS items: hallucination, unusual thought&#xD;
             content and conceptual disorganization.&#xD;
&#xD;
          -  Have not had a psychiatric hospitalization in the two months prior to screening.&#xD;
&#xD;
          -  Be taking any 1st generation antipsychotic prescribed in the absence of a concomitant&#xD;
             anticholinergic or 2nd generation antipsychotic and minimal extrapyramidal symptoms&#xD;
&#xD;
          -  Have a Simpson-Angus Score (SAS) &lt; 6&#xD;
&#xD;
          -  Be on current medication regimen for at least six weeks before screening at stable&#xD;
             dose and frequency for at least 30 days before screening.&#xD;
&#xD;
          -  Be in good general health and expected to complete the clinical study as designed.&#xD;
&#xD;
          -  Subjects of childbearing potential must agree to use two forms of non-hormonal&#xD;
             contraception (dual contraception) consistently during the screening and treatment&#xD;
             periods of the trial, and for 30 days after the final dose of the study medications.&#xD;
&#xD;
          -  Females of child-bearing potential must have a negative urine pregnancy test at&#xD;
             baseline. This may also be done at subsequent visits if subject reports possibility of&#xD;
             pregnancy.&#xD;
&#xD;
          -  Have a negative urine drug screen at screening. This may be repeated at the discretion&#xD;
             of the primary investigator.&#xD;
&#xD;
          -  Have adequate hearing, vision, and language skills to perform the procedures specified&#xD;
             in the protocol.&#xD;
&#xD;
          -  Be capable of providing informed consent and have voluntarily provided informed&#xD;
             consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Have an active, clinically significant unstable medical condition with 30 days prior&#xD;
             to screening.&#xD;
&#xD;
          -  Have dementia.&#xD;
&#xD;
          -  Are pregnant, breastfeeding, or planning to become pregnant&#xD;
&#xD;
          -  Are taking or thinking about taking oral contraceptives or an injectable&#xD;
             contraceptive.&#xD;
&#xD;
          -  Are taking benztropine at a dose greater than 2 mg daily.&#xD;
&#xD;
          -  Have a history of Pervasive Development Disorder.&#xD;
&#xD;
          -  Have a history of significant head injury/trauma (defined by one of more of the&#xD;
             following: loss of consciousness for more than one hour; recurring seizures resulting&#xD;
             from the head injury; and/or clear cognitive sequelae of the injury requiring&#xD;
             cognitive rehabilitation.)&#xD;
&#xD;
          -  Have an allergy to anticholinesterase medications (galantamine, rivastigimine,&#xD;
             donepezil) and memantine&#xD;
&#xD;
          -  Have a DSM-5 diagnosis of alcohol and/or substance use disorder (other than caffeine&#xD;
             and tobacco) within the last 6 months.&#xD;
&#xD;
          -  Are taking a restricted medication: Amitriptyline, Doxepin, Imipramine, Flexeril,&#xD;
             Clozapine, and/or cortisol (any oral, injectable, or topical steroid medication)&#xD;
&#xD;
          -  Have a history of seizures excluding a childhood febrile seizure&#xD;
&#xD;
          -  Have received ECT within the last three months prior to screening.&#xD;
&#xD;
          -  Have participated in a clinical trial of any other psychotropic medication within last&#xD;
             two months prior to screening.&#xD;
&#xD;
          -  Have a &quot;severe&quot; or &quot;extremely severe&quot; severity rating on the BPRS items: hallucination&#xD;
             or unusual thought content.&#xD;
&#xD;
          -  Have more than a &quot;moderate&quot; severity rating on the BPRS item conceptual&#xD;
             disorganization .&#xD;
&#xD;
          -  Are currently taking 3 or more antipsychotic medications.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>55 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Maju M. Koola, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Sheppard Pratt Health System</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Sheppard Pratt Health System</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21204</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Koola MM, Buchanan RW, Pillai A, Aitchison KJ, Weinberger DR, Aaronson ST, Dickerson FB. Potential role of the combination of galantamine and memantine to improve cognition in schizophrenia. Schizophr Res. 2014 Aug;157(1-3):84-9. doi: 10.1016/j.schres.2014.04.037. Epub 2014 May 28.</citation>
    <PMID>24878431</PMID>
  </reference>
  <reference>
    <citation>Koola MM. Kynurenine pathway and cognitive impairments in schizophrenia: Pharmacogenetics of galantamine and memantine. Schizophr Res Cogn. 2016 Jun;4:4-9. doi: 10.1016/j.scog.2016.02.001.</citation>
    <PMID>27069875</PMID>
  </reference>
  <results_reference>
    <citation>Koola MM, Sklar J, Davis W, Nikiforuk A, Meissen JK, Sawant-Basak A, Aaronson ST, Kozak R. Kynurenine pathway in schizophrenia: Galantamine-memantine combination for cognitive impairments. Schizophr Res. 2018 Mar;193:459-460. doi: 10.1016/j.schres.2017.07.005. Epub 2017 Jul 11. No abstract available.</citation>
    <PMID>28705532</PMID>
  </results_reference>
  <verification_date>October 2016</verification_date>
  <study_first_submitted>September 4, 2014</study_first_submitted>
  <study_first_submitted_qc>September 5, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 9, 2014</study_first_posted>
  <results_first_submitted>October 5, 2017</results_first_submitted>
  <results_first_submitted_qc>November 6, 2017</results_first_submitted_qc>
  <results_first_posted type="Actual">November 9, 2017</results_first_posted>
  <last_update_submitted>November 6, 2017</last_update_submitted>
  <last_update_submitted_qc>November 6, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">November 9, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Sheppard Pratt Health System</investigator_affiliation>
    <investigator_full_name>Maju Koola</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Schizophrenia</keyword>
  <keyword>Schizoaffective Disorder</keyword>
  <keyword>Cognition</keyword>
  <keyword>Cognitive Impairment</keyword>
  <keyword>Galantamine</keyword>
  <keyword>Memantine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Schizophrenia</mesh_term>
    <mesh_term>Cognitive Dysfunction</mesh_term>
    <mesh_term>Psychotic Disorders</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Memantine</mesh_term>
    <mesh_term>Galantamine</mesh_term>
  </intervention_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Galantamine ER, Memantine XR</title>
          <description>Week 1, Galantamine ER 8 mg HS &amp; Memantine XR 7 mg HS Week 2, Galantamine ER 16 mg HS &amp; Memantine XR 14 mg HS Weeks 3-6, Galantamine ER 24 mg HS &amp; Memantine XR 21 mg HS&#xD;
Galantamine ER&#xD;
Memantine XR</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Galantamine ER, Memantine XR</title>
          <description>Week 1, Galantamine ER 8 mg HS &amp; Memantine XR 7 mg HS Week 2, Galantamine ER 16 mg HS &amp; Memantine XR 14 mg HS Weeks 3-6, Galantamine ER 24 mg HS &amp; Memantine XR 21 mg HS&#xD;
Galantamine ER&#xD;
Memantine XR</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="3"/>
          </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </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>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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>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="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Level of Cognition</title>
        <description>The primary outcome measure will be the change in level of cognition as measured by the MATRICS Consensus Cognitive Battery (MCCB). In schizophrenia, usual composite scores are 20-39. In healthy controls, usual composite scores are normalized to 40-60. Higher values of composite scores mean better cognition. Test scores are normalized to healthy controls, therefore no min-max range is available. Final scores calculated by MATRICS Consensus Cognitive Battery software. Exact minimum/maximum are not known to provider. Overall composite scores are reported.</description>
        <time_frame>Baseline and 6-Weeks</time_frame>
        <population>Participant 3 only provided baseline data</population>
        <group_list>
          <group group_id="O1">
            <title>Galantamine ER, Memantine XR</title>
            <description>Week 1, Galantamine ER 8 mg HS &amp; Memantine XR 7 mg HS Week 2, Galantamine ER 16 mg HS &amp; Memantine XR 14 mg HS Weeks 3-6, Galantamine ER 24 mg HS &amp; Memantine XR 21 mg HS&#xD;
Galantamine ER&#xD;
Memantine XR</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Level of Cognition</title>
          <description>The primary outcome measure will be the change in level of cognition as measured by the MATRICS Consensus Cognitive Battery (MCCB). In schizophrenia, usual composite scores are 20-39. In healthy controls, usual composite scores are normalized to 40-60. Higher values of composite scores mean better cognition. Test scores are normalized to healthy controls, therefore no min-max range is available. Final scores calculated by MATRICS Consensus Cognitive Battery software. Exact minimum/maximum are not known to provider. Overall composite scores are reported.</description>
          <population>Participant 3 only provided baseline data</population>
          <units>units on a scale</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6 Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="48"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week 6 Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline Participant 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Free Tryptophan (TRP)</title>
        <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate.</description>
        <time_frame>Baseline and 6-Weeks</time_frame>
        <population>Participant 3 only provided baseline data</population>
        <group_list>
          <group group_id="O1">
            <title>KP Metabolites Values</title>
          </group>
        </group_list>
        <measure>
          <title>Free Tryptophan (TRP)</title>
          <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate.</description>
          <population>Participant 3 only provided baseline data</population>
          <units>µM</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline tryptophan Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="51.94" spread="2.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week-6 tryptophan Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="55.72" spread="2.83"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline tryptophan Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="32.17" spread="1.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week-6 tryptophan Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.96" spread="1.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline tryptophan Participant 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="35.07" spread="1.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kynurenic Acid (KYNA)</title>
        <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. MS* AUC is mass spectrometry times area under the curve.</description>
        <time_frame>Baseline and 6-Weeks</time_frame>
        <population>Participant 3 only provided baseline data</population>
        <group_list>
          <group group_id="O1">
            <title>KP Metabolites Values</title>
          </group>
        </group_list>
        <measure>
          <title>Kynurenic Acid (KYNA)</title>
          <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. MS* AUC is mass spectrometry times area under the curve.</description>
          <population>Participant 3 only provided baseline data</population>
          <units>MS* AUC</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline KYNA Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="103911" spread="20870"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week-6 KYNA Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="83737" spread="25309"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline KYNA Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="95139" spread="36663"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week-6 KYNA Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="73280" spread="15567"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline KYNA Participant 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="93163" spread="41519"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Kynurenine (KYN)</title>
        <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate.</description>
        <time_frame>Baseline and 6-Weeks</time_frame>
        <population>Participant 3 only provided baseline data</population>
        <group_list>
          <group group_id="O1">
            <title>KP Metabolites Values</title>
          </group>
        </group_list>
        <measure>
          <title>Kynurenine (KYN)</title>
          <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate.</description>
          <population>Participant 3 only provided baseline data</population>
          <units>µM</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline KYN Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.62" spread="0.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week-6 KYN Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.85" spread="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline KYN Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.86" spread="0.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week-6 KYN Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.71" spread="0.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline KYN Participant 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.76" spread="0.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Picolinic Acid (PIC)</title>
        <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. MS* AUC is mass spectrometry times area under the curve.</description>
        <time_frame>Baseline and 6-Weeks</time_frame>
        <population>Participant 3 only provided baseline data</population>
        <group_list>
          <group group_id="O1">
            <title>KP Metabolites Values</title>
          </group>
        </group_list>
        <measure>
          <title>Picolinic Acid (PIC)</title>
          <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. MS* AUC is mass spectrometry times area under the curve.</description>
          <population>Participant 3 only provided baseline data</population>
          <units>MS* AUC</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline PIC Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="44021" spread="4470"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week-6 PIC Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29542" spread="383"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline PIC Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="81883" spread="7344"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week-6 PIC Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="63745" spread="1535"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline PIC Participant 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="40189" spread="4342"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>KYN/TRP</title>
        <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.</description>
        <time_frame>Baseline and 6-Weeks</time_frame>
        <population>Participant 3 only provided baseline data</population>
        <group_list>
          <group group_id="O1">
            <title>KP Metabolites Values</title>
          </group>
        </group_list>
        <measure>
          <title>KYN/TRP</title>
          <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.</description>
          <population>Participant 3 only provided baseline data</population>
          <units>AUC Ratio</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline KYN/TRP Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week-6 KYN/TRP Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.31"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline KYN/TRP Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week-6 KYN/TRP Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline KYN/TRP Participant 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.79"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>KYNA/KYN</title>
        <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.</description>
        <time_frame>Baseline and 6-Weeks</time_frame>
        <population>Participant 3 only provided baseline data</population>
        <group_list>
          <group group_id="O1">
            <title>KP Metabolites Values</title>
          </group>
        </group_list>
        <measure>
          <title>KYNA/KYN</title>
          <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.</description>
          <population>Participant 3 only provided baseline data</population>
          <units>AUC Ratio</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline KYNA/KYN Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.075"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week-6 KYNA/KYN Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.050"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline KYNA/KYN Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.121"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week-6 KYNA/KYN Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.114"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline KYNA/KYN Participant 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.152"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>PIC/KYN</title>
        <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.</description>
        <time_frame>Baseline and 6-Weeks</time_frame>
        <population>Participant 3 only provided baseline data</population>
        <group_list>
          <group group_id="O1">
            <title>KP Metabolites Values</title>
          </group>
        </group_list>
        <measure>
          <title>PIC/KYN</title>
          <description>The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.</description>
          <population>Participant 3 only provided baseline data</population>
          <units>AUC Ratio</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="3"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline PIC/KYN Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0317"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week-6 PIC/KYN Participant 1</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0175"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline PIC/KYN Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.1039"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Week-6 PIC/KYN Participant 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0989"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline PIC/KYN Participant 3</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.0655"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Galantamine ER, Memantine XR</title>
          <description>Week 1, Galantamine ER 8 mg HS &amp; Memantine XR 7 mg HS Week 2, Galantamine ER 16 mg HS &amp; Memantine XR 14 mg HS Weeks 3-6, Galantamine ER 24 mg HS &amp; Memantine XR 21 mg HS&#xD;
Galantamine ER&#xD;
Memantine XR</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="3"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</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="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Constipation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Diarrhea</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Increased tiredness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Lightheadedness</sub_title>
                <counts group_id="E1" events="3" subjects_affected="1" subjects_at_risk="3"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="3"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Maju Koola</name_or_title>
      <organization>George Washington University, Washington, DC</organization>
      <phone>678-200-8613</phone>
      <email>majumkoola@gmail.com</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/NCT02234752
org study id: SPHS IRB # 604148-4
nct id: NCT02234752
lead sponsor: 
has dmc: Yes
Aim: To examine the efficacy of the combination of galantamine and memantine for the
      treatment of cognitive deficits in outpatients with schizophrenia.

      Hypothesis: A combination of galantamine and memantine will improve cognitive impairments in
      patients with schizophrenia.

      This is an open-label study to evaluate whether a six week course of galantamine ER and
      memantine XR is effective in improving the cognitive performance of patients with
      schizophrenia or schizoaffective disorder. The primary outcome measure will be the change in
      level of cognition as measured by the MATRICS Consensus Cognitive Battery (MCCB). The results
      of the MATRICS collaborative project recommended the need for standardized cognitive tests
      that better distinguish the different facets of cognitive dysfunction in schizophrenia. The
      MCCB will assess the following seven domains: attention/vigilance, reasoning and problem
      solving, processing speed, social cognition, verbal learning and memory, visual learning and
      memory, and working memory. The MCCB will be administered at baseline and at the end of the
      study. We will report total score and each domain score in the MCCB at baseline and six
      weeks.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in Level of Cognition
time frame: Baseline and 6-Weeks
description: The primary outcome measure will be the change in level of cognition as measured by the MATRICS Consensus Cognitive Battery (MCCB). In schizophrenia, usual composite scores are 20-39. In healthy controls, usual composite scores are normalized to 40-60. Higher values of composite scores mean better cognition. Test scores are normalized to healthy controls, therefore no min-max range is available. Final scores calculated by MATRICS Consensus Cognitive Battery software. Exact minimum/maximum are not known to provider. Overall composite scores are reported.
measure: Free Tryptophan (TRP)
time frame: Baseline and 6-Weeks
description: The secondary outcome measure will be change in metabolite values. Values were collected in triplicate.
measure: Kynurenic Acid (KYNA)
time frame: Baseline and 6-Weeks
description: The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. MS* AUC is mass spectrometry times area under the curve.
measure: Kynurenine (KYN)
time frame: Baseline and 6-Weeks
description: The secondary outcome measure will be change in metabolite values. Values were collected in triplicate.
measure: Picolinic Acid (PIC)
time frame: Baseline and 6-Weeks
description: The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. MS* AUC is mass spectrometry times area under the curve.
measure: KYN/TRP
time frame: Baseline and 6-Weeks
description: The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.
measure: KYNA/KYN
time frame: Baseline and 6-Weeks
description: The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.
measure: PIC/KYN
time frame: Baseline and 6-Weeks
description: The secondary outcome measure will be change in metabolite values. Values were collected in triplicate. AUC ratio reported.
arm group label: Galantamine ER, Memantine XR
arm group type: Experimental
description: Week 1, Galantamine ER 8 mg HS & Memantine XR 7 mg HS Week 2, Galantamine ER 16 mg HS & Memantine XR 14 mg HS Weeks 3-6, Galantamine ER 24 mg HS & Memantine XR 21 mg HS
intervention type: Drug
intervention name: Galantamine ER
arm group label: Galantamine ER, Memantine XR
other name: Razadyne
other name: Razadyne ER
other name: Formerly known as Reminyl
intervention type: Drug
intervention name: Memantine XR
arm group label: Galantamine ER, Memantine XR
other name: Namenda
criteria: 
gender: All
minimum age: 18 Years
maximum age: 55 Years
healthy volunteers: No
last name: Maju M. Koola, MD
role: Principal Investigator
affiliation: Sheppard Pratt Health System
facility: 
country: United States
citation: Koola MM, Buchanan RW, Pillai A, Aitchison KJ, Weinberger DR, Aaronson ST, Dickerson FB. Potential role of the combination of galantamine and memantine to improve cognition in schizophrenia. Schizophr Res. 2014 Aug;157(1-3):84-9. doi: 10.1016/j.schres.2014.04.037. Epub 2014 May 28.
PMID: 24878431
citation: Koola MM. Kynurenine pathway and cognitive impairments in schizophrenia: Pharmacogenetics of galantamine and memantine. Schizophr Res Cogn. 2016 Jun;4:4-9. doi: 10.1016/j.scog.2016.02.001.
PMID: 27069875
citation: Koola MM, Sklar J, Davis W, Nikiforuk A, Meissen JK, Sawant-Basak A, Aaronson ST, Kozak R. Kynurenine pathway in schizophrenia: Galantamine-memantine combination for cognitive impairments. Schizophr Res. 2018 Mar;193:459-460. doi: 10.1016/j.schres.2017.07.005. Epub 2017 Jul 11. No abstract available.
PMID: 28705532
responsible party type: Principal Investigator
investigator affiliation: Sheppard Pratt Health System
investigator full name: Maju Koola
investigator title: Principal Investigator
mesh term: Schizophrenia
mesh term: Cognitive Dysfunction
mesh term: Psychotic Disorders
mesh term: Memantine
mesh term: Galantamine
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 