<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/NCT02197104</url>
  </required_header>
  <id_info>
    <org_study_id>CITO-123</org_study_id>
    <nct_id>NCT02197104</nct_id>
  </id_info>
  <brief_title>Citocoline for Treatment in Fragile X-associated Tremor/Ataxia Syndrome</brief_title>
  <official_title>Phase 2 Study of Citocoline for Treatment in Fragile X-associated Tremor/Ataxia Syndrome</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rush University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rush University Medical Center</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to determine if citocoline is effective for balance&#xD;
      abnormalities and to stabilize cognitive decline in patients with fragile X-associated tremor&#xD;
      ataxia syndrome. The study will test 1000mg twice daily of citocoline for 12 months in an&#xD;
      open label pilot study, with study visits at baseline, 3, 6, and 12 months.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study was to determine if citicoline was safe for the treatment of tremor&#xD;
      and balance abnormalities and to stabilize cognitive decline in patients with fragile&#xD;
      X-associated tremor ataxia syndrome. Ten participants with diagnosed FXTAS were administered&#xD;
      1000 mg of citicoline once daily for 12 months. Outcome measures and neurological examination&#xD;
      were performed at baseline, 3 months, 6 months, and 12 months. The primary outcome was&#xD;
      safety. Secondary outcomes included change in FXTAS Rating Scale score, a battery of&#xD;
      neuropsychological tests, an instrumented Timed up and go test, computerized dynamic&#xD;
      posturography, 9-hole pegboard test, and balance confidence and psychiatric symptom&#xD;
      questionnaires.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>January 2015</start_date>
  <completion_date type="Actual">January 2017</completion_date>
  <primary_completion_date type="Actual">January 2017</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>FXTAS Rating Scale Score</measure>
    <time_frame>12 months</time_frame>
    <description>The FXTAS Rating Scale (FXTAS-RS), which was designed to measure the severity of motor signs in FXTAS patients, was administered to each participant. The FXTAS-RS was designed to measure the severity of motor signs of FXTAS, tremor, ataxia, and parkinsonism. The scale was developed from a combination of three separate measures: the Clinical Rating Scale for Tremor (CRST), the International Cooperative Ataxia Rating Scale (ICARS), and the Unified Parkinson's Disease Rating Scale (UPDRS). The resultant scale has 44 items and a possible total score of 0-226. A higher score indicates worse symptoms. For this study, improvement was defined as a 20% improvement on the FXTAS-RS.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Fragile X Tremor/Ataxia Syndrome</condition>
  <arm_group>
    <arm_group_label>Citocoline</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The intervention will be 1000mg of citicoline in capsule form once daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>citocoline</intervention_name>
    <description>Ten subjects will receive 1,000mg once daily of citicoline. Each subject will stay on the study drug for 12 months. The outcome measures will be assessed at baseline and then again at the end of month 3, month 6, and month 12. The subjects will continue taking the same study drug at the same dose throughout the entire trial.</description>
    <arm_group_label>Citocoline</arm_group_label>
    <other_name>CDP-choline</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Clinical diagnosis of FXTAS&#xD;
&#xD;
               -  Serum creatine kinase, complete metabolic panel, complete blood count, liver&#xD;
                  function tests, renal function tests, platelets and EKG are within normal limits&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Legal incapacity or limited legal capacity&#xD;
&#xD;
          -  Presence of severe renal disease (BUN 50% greater than normal or creatinine clearance&#xD;
             &lt;60 mL/min) or hepatic disease.&#xD;
&#xD;
          -  Abnormal creatine kinase and/or platelet count in the past 6 months (as determined by&#xD;
             lab reports obtained from primary care physicians or conducted at baseline).&#xD;
&#xD;
          -  Women of childbearing potential who are pregnant at the time of screening or who will&#xD;
             not use adequate protection during participation of the study.&#xD;
&#xD;
          -  Allergy/sensitivity to the drug of its formulations.&#xD;
&#xD;
          -  Concurrent participation in another clinical study.&#xD;
&#xD;
          -  Active substance use or dependence.&#xD;
&#xD;
          -  Serious illness (requiring systematic treatment/or hospitalization) until the subject&#xD;
             either completes therapy or is clinically stable on therapy, in the opinion of the&#xD;
             site investigator, for at least 60 days prior to study entry.&#xD;
&#xD;
          -  Inability or unwillingness of the subject or legal guardian/representative to give&#xD;
             written informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Deborah A Hall, MD PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rush University Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Rush University Medical Center</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60612</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>July 14, 2014</study_first_submitted>
  <study_first_submitted_qc>July 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 22, 2014</study_first_posted>
  <results_first_submitted>August 31, 2020</results_first_submitted>
  <results_first_submitted_qc>November 1, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">November 2, 2022</results_first_posted>
  <last_update_submitted>November 1, 2022</last_update_submitted>
  <last_update_submitted_qc>November 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">November 2, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rush University Medical Center</investigator_affiliation>
    <investigator_full_name>Deborah Hall, MD</investigator_full_name>
    <investigator_title>Associate Professor Neurological Sciences</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ataxia</mesh_term>
    <mesh_term>Cerebellar Ataxia</mesh_term>
    <mesh_term>Tremor</mesh_term>
    <mesh_term>Syndrome</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Choline</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>January 12, 2015</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/04/NCT02197104/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Citocoline</title>
          <description>All participants received 1,000mg once daily of citicoline. Each subject will stay on the study drug for 12 months. The outcome measures will be assessed at baseline and then again at the end of month 3, month 6, and month 12. The subjects will continue taking the same study drug at the same dose throughout the entire trial.</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_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
              </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>Citocoline</title>
          <description>All participants were white and non-Hispanic; there were nine men and one woman. This distribution is expected as there is a lower penetrance of FXTAS in women from X-inactivation. The subject with probable FXTAS was also the female subject. Nine participants completed the one-year follow-up and one participant with a low platelet count withdrew prior to the end of the study and outcome data was missing for this participant at 12 months, but all available data were used for analysis.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="10"/>
          </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="70" spread="7.33"/>
                  </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="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                  </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>
                  <title>Midwestern</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                  </measurement_list>
                </category>
                <category>
                  <title>East Coast</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>FXTAS Rating Scale Score</title>
        <description>The FXTAS Rating Scale (FXTAS-RS), which was designed to measure the severity of motor signs in FXTAS patients, was administered to each participant. The FXTAS-RS was designed to measure the severity of motor signs of FXTAS, tremor, ataxia, and parkinsonism. The scale was developed from a combination of three separate measures: the Clinical Rating Scale for Tremor (CRST), the International Cooperative Ataxia Rating Scale (ICARS), and the Unified Parkinson's Disease Rating Scale (UPDRS). The resultant scale has 44 items and a possible total score of 0-226. A higher score indicates worse symptoms. For this study, improvement was defined as a 20% improvement on the FXTAS-RS.</description>
        <time_frame>12 months</time_frame>
        <population>9 patients with FXTAS who participated in the study for 12 months were analyzed.</population>
        <group_list>
          <group group_id="O1">
            <title>Citocoline</title>
            <description>Experimental group given the study drug, citocoline</description>
          </group>
        </group_list>
        <measure>
          <title>FXTAS Rating Scale Score</title>
          <description>The FXTAS Rating Scale (FXTAS-RS), which was designed to measure the severity of motor signs in FXTAS patients, was administered to each participant. The FXTAS-RS was designed to measure the severity of motor signs of FXTAS, tremor, ataxia, and parkinsonism. The scale was developed from a combination of three separate measures: the Clinical Rating Scale for Tremor (CRST), the International Cooperative Ataxia Rating Scale (ICARS), and the Unified Parkinson's Disease Rating Scale (UPDRS). The resultant scale has 44 items and a possible total score of 0-226. A higher score indicates worse symptoms. For this study, improvement was defined as a 20% improvement on the FXTAS-RS.</description>
          <population>9 patients with FXTAS who participated in the study for 12 months were analyzed.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.8" spread="21.22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>12 months</time_frame>
      <desc>Adverse event information was collected at baseline and then again at the end of month 3, month 6, and month 12.</desc>
      <group_list>
        <group group_id="E1">
          <title>Citocoline</title>
          <description>All participants received citocoline.</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"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastrointestinal disorders</sub_title>
                <description>Diarrhea, vomiting, elevated liver enzymes</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Immune system disorders</title>
            <event_list>
              <event>
                <sub_title>Low platelet count</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Falls</sub_title>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="10"/>
              </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="5" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Blood and lymphatic system disorders</title>
            <event_list>
              <event>
                <sub_title>Bruising</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
              <event>
                <sub_title>Leg edema</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Weight gain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="10"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Deborah A Hall</name_or_title>
      <organization>Rush University Medical Center</organization>
      <phone>312-563-2900</phone>
      <email>Movementdisorder@rush.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/NCT02197104
org study id: CITO-123
nct id: NCT02197104
lead sponsor: 
has dmc: Yes
The objective of this study is to determine if citocoline is effective for balance
      abnormalities and to stabilize cognitive decline in patients with fragile X-associated tremor
      ataxia syndrome. The study will test 1000mg twice daily of citocoline for 12 months in an
      open label pilot study, with study visits at baseline, 3, 6, and 12 months.
The purpose of this study was to determine if citicoline was safe for the treatment of tremor
      and balance abnormalities and to stabilize cognitive decline in patients with fragile
      X-associated tremor ataxia syndrome. Ten participants with diagnosed FXTAS were administered
      1000 mg of citicoline once daily for 12 months. Outcome measures and neurological examination
      were performed at baseline, 3 months, 6 months, and 12 months. The primary outcome was
      safety. Secondary outcomes included change in FXTAS Rating Scale score, a battery of
      neuropsychological tests, an instrumented Timed up and go test, computerized dynamic
      posturography, 9-hole pegboard test, and balance confidence and psychiatric symptom
      questionnaires.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: FXTAS Rating Scale Score
time frame: 12 months
description: The FXTAS Rating Scale (FXTAS-RS), which was designed to measure the severity of motor signs in FXTAS patients, was administered to each participant. The FXTAS-RS was designed to measure the severity of motor signs of FXTAS, tremor, ataxia, and parkinsonism. The scale was developed from a combination of three separate measures: the Clinical Rating Scale for Tremor (CRST), the International Cooperative Ataxia Rating Scale (ICARS), and the Unified Parkinson's Disease Rating Scale (UPDRS). The resultant scale has 44 items and a possible total score of 0-226. A higher score indicates worse symptoms. For this study, improvement was defined as a 20% improvement on the FXTAS-RS.
arm group label: Citocoline
arm group type: Experimental
description: The intervention will be 1000mg of citicoline in capsule form once daily.
intervention type: Drug
intervention name: citocoline
description: Ten subjects will receive 1,000mg once daily of citicoline. Each subject will stay on the study drug for 12 months. The outcome measures will be assessed at baseline and then again at the end of month 3, month 6, and month 12. The subjects will continue taking the same study drug at the same dose throughout the entire trial.
arm group label: Citocoline
other name: CDP-choline
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Deborah A Hall, MD PhD
role: Principal Investigator
affiliation: Rush University Medical Center
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Rush University Medical Center
investigator full name: Deborah Hall, MD
investigator title: Associate Professor Neurological Sciences
mesh term: Ataxia
mesh term: Cerebellar Ataxia
mesh term: Tremor
mesh term: Syndrome
mesh term: Choline
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 