xml: <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/NCT06029894</url>
    </required_header>
    <id_info>
      <org_study_id>STUDY00006047</org_study_id>
      <secondary_id>1R61AG080606-01</secondary_id>
      <nct_id>NCT06029894</nct_id>
    </id_info>
    <brief_title>Improving Sleep and AD Biomarkers</brief_title>
    <official_title>Improving Sleep and Alzheimer's Disease (AD) Biomarkers: A Pilot Randomized Clinical Trial (RCT) of Citicoline</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Emory University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>National Institute on Aging (NIA)</agency>
        <agency_class>NIH</agency_class>
      </collaborator>
    </sponsors>
    <source>Emory University</source>
    <oversight_info>
      <has_dmc>Yes</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of this research is to learn whether a dietary citicoline supplement will impact&#xD;
        sleep and cognition. Cognitive disorders include such things as memory disorders and mild&#xD;
        cognitive impairment. The investigators are studying persons with mild cognitive impairment&#xD;
        (MCI). For this population, the team will assess whether citicoline also impacts biomarkers,&#xD;
        a marker of the patient's biological state, in their body.&#xD;
  &#xD;
        The investigators are interested in learning more about a dietary supplement called&#xD;
        citicoline and how it helps sleep, cognition, and markers of Alzheimer's. Previous studies&#xD;
        have evaluated this dietary supplement and shown that citicoline may impact cognitive&#xD;
        decline. The investigator would like to evaluate if citicoline will also impact sleep and&#xD;
        markers of Alzheimer's. This dietary supplement has been assessed in older adults and found&#xD;
        to be well tolerated. Citicoline has been used safely in cognitive impairment populations at&#xD;
        the same dosage.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is a randomized double-blind placebo-controlled pilot trial. To assess the hypothesis in&#xD;
        this proposed study, the investigator will leverage infrastructure from the Emory Alzheimer's&#xD;
        disease research center (ADRC), ADRC-affiliated centers, mild cognitive impairment, related&#xD;
        research cohorts with potential eligible participants interested in participating in future&#xD;
        studies, the Emory Sleep Center, and also recruit from the community. The research team will&#xD;
        be actively recruiting individuals with MCI with confirmed medical diagnoses. The&#xD;
        investigator will also collect data from personal interviews on prior medical diagnoses from&#xD;
        the medical record along with current medication usage. Researchers will also obtain&#xD;
        available baseline AD biomarker data from participants at baseline if they have cerebrospinal&#xD;
        fluid (CSF) and/or blood data available on AD biomarkers within the past year from prior&#xD;
        research studies, the investigators will use this data for the study records which will serve&#xD;
        as their 'baseline' AD biomarker level). AD biomarkers of interest include Amyloid-Beta 1-42&#xD;
        (Aβ42), t-tau, and P-tau181. Should participants not have this data available at baseline,&#xD;
        the research team will conduct a blood draw for AD biomarker levels at baseline and at&#xD;
        follow-up.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 2023</start_date>
    <completion_date type="Anticipated">December 2024</completion_date>
    <primary_completion_date type="Anticipated">December 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
      <masking_description>Citicoline and placebo treatment will be blinded. The study treatment will be labeled using a unique Kit ID number that is linked to a randomization scheme. The active and placebo tablets will be identical and presented in the same packaging to ensure the blinding of the study medication.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Change in the Pittsburgh Sleep Quality Index (PSQI)</measure>
      <time_frame>Baseline and 3 months</time_frame>
      <description>This questionnaire is used to measure subjective sleep quality. It has strong validity and reliability in clinical populations and consists of 19 items asking about sleep disturbances over the past month with 7 dimensions. Each dimension scores 0 (no difficulty) to 3 (severe difficulty) and the sum of these scores yields a global sleep quality score that ranges from 0-21. Higher scores indicate greater difficulty sleeping. This questionnaire can be filled out by the participant, caregiver, or both as appropriate.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in the Epworth Sleepiness Scale (ESS)</measure>
      <time_frame>Baseline and 3 months</time_frame>
      <description>The ESS is a clinical and research standard used to assess perceived daytime sleepiness over the past month. It is a self-administered validated questionnaire and takes 2-3 minutes to fill out. Respondents are asked to rate how likely they are to doze off in 8 situations, from 0 (would never dose) to 3 (high chance of dozing). Any score of 10 or above is considered an indicator of pathologic sleepiness. This questionnaire can be filled out by the participant, caregiver, or both as appropriate.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in percentage of the rapid eye movement (REM) sleep</measure>
      <time_frame>Baseline and 3 months</time_frame>
      <description>The change in % REM sleep will be measured using The Sleep Profiler using the polysomnography 2 (PSG2), which is an Electroencephalogram (EEG) Sleep Monitor that is an FDA-cleared, easily applied, wireless EEG device developed and validated to measure sleep architecture for in-home sleep studies. This will be worn for 2 nights at baseline and again for 2 nights at follow-up.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in sleep duration</measure>
      <time_frame>Baseline and 3 months</time_frame>
      <description>Average sleep duration (hours) will be measured via a subjective 7-day sleep diary that collects subjective sleep/wake patterns and naps. It is the &quot;gold standard&quot; for subjective sleep assessment of sleep duration. It will be filled out by the participant in conjunction with the caregiver.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in plasma choline levels</measure>
      <time_frame>Baseline and 3 months</time_frame>
      <description>Blood draws will be made at baseline and follow-up.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in beta-amyloid 42 levels</measure>
      <time_frame>Baseline and 3 months</time_frame>
      <description>Levels of beta-amyloid 42. A lumbar puncture (LP) will be performed at 3 months in participants who have already had a previous LP. For those who don't have a previous LP performed, blood samples will be drawn before starting the study medication and at follow-up.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change in tau and phospho-tau levels</measure>
      <time_frame>Baseline and 3 months</time_frame>
      <description>Levels of tau, and phospho-tau will be measured. A lumbar puncture (LP) will be performed at 3 months in participants who have already had a previous LP. For those who don't have a previous LP performed, blood samples will be drawn before starting the study medication and at follow-up.</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">100</enrollment>
    <condition>Mild Cognitive Impairment</condition>
    <condition>Alzheimer Disease</condition>
    <arm_group>
      <arm_group_label>Treatment Group</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Participants with MCI will receive dietary citicoline supplements.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Placebo</arm_group_label>
      <arm_group_type>Placebo Comparator</arm_group_type>
      <description>Participants with MCI will receive a placebo supplement.</description>
    </arm_group>
    <intervention>
      <intervention_type>Dietary Supplement</intervention_type>
      <intervention_name>Citicoline Supplement</intervention_name>
      <description>Participants with MCI will receive dietary citicoline supplements. Subjective sleep measures will be measured via the Pittsburgh Sleep Quality Index (for measurement of sleep quality) and Epworth Sleepiness Scale (for measurement of sleepiness). Cognition will be measured by Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT) Parts A &amp; B, and the Montreal Cognitive Assessment (MOCA). Participants will complete all questionnaires at baseline and at follow-up at 3 months. Participants will undergo a blood draw of approximately 20 ml at baseline and at follow-up.</description>
      <arm_group_label>Treatment Group</arm_group_label>
      <other_name>Citicoline 1000mg</other_name>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Placebo</intervention_name>
      <description>Participants with MCI will receive a placebo supplement. Subjective sleep measures will be measured via the Pittsburgh Sleep Quality Index (for measurement of sleep quality) and Epworth Sleepiness Scale (for measurement of sleepiness). Cognition will be measured by Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT) Parts A &amp; B, and the Montreal Cognitive Assessment (MOCA). Participants will complete all questionnaires at baseline and at follow-up at 3 months. Participants will undergo a blood draw of approximately 20 ml at baseline and at follow-up.</description>
      <arm_group_label>Placebo</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  Age: 60 years or older&#xD;
  &#xD;
            -  Diagnosis of Mild Cognitive Impairment (MCI)&#xD;
  &#xD;
            -  Pittsburgh Sleep Quality Index total score &gt;5 or Epworth Sleepiness Scale score of ≥&#xD;
               10&#xD;
  &#xD;
            -  Read and understand English&#xD;
  &#xD;
            -  Have Internet and email access&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  No telephone access&#xD;
  &#xD;
            -  Must not be taking any medication known to affect rapid eye movement (REM) sleep (or&#xD;
               sleep architecture in general)&#xD;
  &#xD;
            -  Use of choline supplements.&#xD;
  &#xD;
            -  Epilepsy or head trauma resulting in unconsciousness in the past two years&#xD;
  &#xD;
            -  Known allergic reactions to components of Citicoline&#xD;
  &#xD;
            -  Presence of chronic obstructive pulmonary disease, asthma, severe cardiac&#xD;
               insufficiency (congestive heart failure, myocardial infarction), type I diabetes,&#xD;
               vitamin B12 or folic acid deficiency, liver cirrhosis, thyroid dysfunction, rheumatoid&#xD;
               arthritis, chronic renal failure, severe/unstable psychiatric disorders, moderate to&#xD;
               severe obstructive sleep apnea, restless legs syndrome or periodic limb movement&#xD;
               disorder&#xD;
  &#xD;
            -  History of alcohol dependence and drug abuse&#xD;
  &#xD;
            -  Night shift workers or those in situations where they regularly experience jet lag or&#xD;
               have irregular work schedules&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>60 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Victoria Pak, PhD, MS, MTR</last_name>
      <role>Principal Investigator</role>
      <affiliation>Emory University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Victoria Pak, PhD, MS, MTR</last_name>
      <phone>470-296-0081</phone>
      <email>victoria.m.pak@emory.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>Emory University School of Nursing</name>
        <address>
          <city>Atlanta</city>
          <state>Georgia</state>
          <zip>30322</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location>
      <facility>
        <name>Goizueta Alzheimer's Disease Research Center</name>
        <address>
          <city>Atlanta</city>
          <state>Georgia</state>
          <zip>30329</zip>
          <country>United States</country>
        </address>
      </facility>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 10, 2023</study_first_submitted>
    <study_first_submitted_qc>September 1, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 8, 2023</study_first_posted>
    <last_update_submitted>September 1, 2023</last_update_submitted>
    <last_update_submitted_qc>September 1, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 8, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>Emory University</investigator_affiliation>
      <investigator_full_name>Victoria Pak</investigator_full_name>
      <investigator_title>Assistant Professor</investigator_title>
    </responsible_party>
    <keyword>Dementia</keyword>
    <keyword>Citicoline supplement</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Alzheimer Disease</mesh_term>
      <mesh_term>Cognitive Dysfunction</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Cytidine Diphosphate Choline</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>Yes</sharing_ipd>
      <ipd_description>The research team will share deidentified data in accordance with the NIH Data Sharing Policy to share research resources (biological samples and finalized data). Deidentified data and deidentified biological samples will be stored and shared with other institutions or companies as approved by a Scientific Review Committee and in accordance with all applicable regulations.</ipd_description>
      <ipd_time_frame>Anticipated data availability will be at the conclusion of this study on 7/1/25.</ipd_time_frame>
      <ipd_access_criteria>Data will be shared with the Aging Research Biobank. The data generated in this study will be housed in the Aging Research Biobank. The database can be found at the following link: agingresearchbiobank.nia.nih.gov</ipd_access_criteria>
      <ipd_url>https://agingresearchbiobank.nia.nih.gov</ipd_url>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06029894
  org study id: STUDY00006047
  secondary id: 1R61AG080606-01
  nct id: NCT06029894
  lead sponsor: 
  collaborator: 
  has dmc: Yes
  is fda regulated drug: No
  is fda regulated device: No
  The purpose of this research is to learn whether a dietary citicoline supplement will impact
        sleep and cognition. Cognitive disorders include such things as memory disorders and mild
        cognitive impairment. The investigators are studying persons with mild cognitive impairment
        (MCI). For this population, the team will assess whether citicoline also impacts biomarkers,
        a marker of the patient's biological state, in their body.
  
        The investigators are interested in learning more about a dietary supplement called
        citicoline and how it helps sleep, cognition, and markers of Alzheimer's. Previous studies
        have evaluated this dietary supplement and shown that citicoline may impact cognitive
        decline. The investigator would like to evaluate if citicoline will also impact sleep and
        markers of Alzheimer's. This dietary supplement has been assessed in older adults and found
        to be well tolerated. Citicoline has been used safely in cognitive impairment populations at
        the same dosage.
  This is a randomized double-blind placebo-controlled pilot trial. To assess the hypothesis in
        this proposed study, the investigator will leverage infrastructure from the Emory Alzheimer's
        disease research center (ADRC), ADRC-affiliated centers, mild cognitive impairment, related
        research cohorts with potential eligible participants interested in participating in future
        studies, the Emory Sleep Center, and also recruit from the community. The research team will
        be actively recruiting individuals with MCI with confirmed medical diagnoses. The
        investigator will also collect data from personal interviews on prior medical diagnoses from
        the medical record along with current medication usage. Researchers will also obtain
        available baseline AD biomarker data from participants at baseline if they have cerebrospinal
        fluid (CSF) and/or blood data available on AD biomarkers within the past year from prior
        research studies, the investigators will use this data for the study records which will serve
        as their 'baseline' AD biomarker level). AD biomarkers of interest include Amyloid-Beta 1-42
        (Aβ42), t-tau, and P-tau181. Should participants not have this data available at baseline,
        the research team will conduct a blood draw for AD biomarker levels at baseline and at
        follow-up.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: Double (Participant, Investigator)
  masking description: Citicoline and placebo treatment will be blinded. The study treatment will be labeled using a unique Kit ID number that is linked to a randomization scheme. The active and placebo tablets will be identical and presented in the same packaging to ensure the blinding of the study medication.
  measure: Change in the Pittsburgh Sleep Quality Index (PSQI)
  time frame: Baseline and 3 months
  description: This questionnaire is used to measure subjective sleep quality. It has strong validity and reliability in clinical populations and consists of 19 items asking about sleep disturbances over the past month with 7 dimensions. Each dimension scores 0 (no difficulty) to 3 (severe difficulty) and the sum of these scores yields a global sleep quality score that ranges from 0-21. Higher scores indicate greater difficulty sleeping. This questionnaire can be filled out by the participant, caregiver, or both as appropriate.
  measure: Change in the Epworth Sleepiness Scale (ESS)
  time frame: Baseline and 3 months
  description: The ESS is a clinical and research standard used to assess perceived daytime sleepiness over the past month. It is a self-administered validated questionnaire and takes 2-3 minutes to fill out. Respondents are asked to rate how likely they are to doze off in 8 situations, from 0 (would never dose) to 3 (high chance of dozing). Any score of 10 or above is considered an indicator of pathologic sleepiness. This questionnaire can be filled out by the participant, caregiver, or both as appropriate.
  measure: Change in percentage of the rapid eye movement (REM) sleep
  time frame: Baseline and 3 months
  description: The change in % REM sleep will be measured using The Sleep Profiler using the polysomnography 2 (PSG2), which is an Electroencephalogram (EEG) Sleep Monitor that is an FDA-cleared, easily applied, wireless EEG device developed and validated to measure sleep architecture for in-home sleep studies. This will be worn for 2 nights at baseline and again for 2 nights at follow-up.
  measure: Change in sleep duration
  time frame: Baseline and 3 months
  description: Average sleep duration (hours) will be measured via a subjective 7-day sleep diary that collects subjective sleep/wake patterns and naps. It is the "gold standard" for subjective sleep assessment of sleep duration. It will be filled out by the participant in conjunction with the caregiver.
  measure: Change in plasma choline levels
  time frame: Baseline and 3 months
  description: Blood draws will be made at baseline and follow-up.
  measure: Change in beta-amyloid 42 levels
  time frame: Baseline and 3 months
  description: Levels of beta-amyloid 42. A lumbar puncture (LP) will be performed at 3 months in participants who have already had a previous LP. For those who don't have a previous LP performed, blood samples will be drawn before starting the study medication and at follow-up.
  measure: Change in tau and phospho-tau levels
  time frame: Baseline and 3 months
  description: Levels of tau, and phospho-tau will be measured. A lumbar puncture (LP) will be performed at 3 months in participants who have already had a previous LP. For those who don't have a previous LP performed, blood samples will be drawn before starting the study medication and at follow-up.
  arm group label: Treatment Group
  arm group type: Experimental
  description: Participants with MCI will receive dietary citicoline supplements.
  arm group label: Placebo
  arm group type: Placebo Comparator
  description: Participants with MCI will receive a placebo supplement.
  intervention type: Dietary Supplement
  intervention name: Citicoline Supplement
  description: Participants with MCI will receive dietary citicoline supplements. Subjective sleep measures will be measured via the Pittsburgh Sleep Quality Index (for measurement of sleep quality) and Epworth Sleepiness Scale (for measurement of sleepiness). Cognition will be measured by Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT) Parts A & B, and the Montreal Cognitive Assessment (MOCA). Participants will complete all questionnaires at baseline and at follow-up at 3 months. Participants will undergo a blood draw of approximately 20 ml at baseline and at follow-up.
  arm group label: Treatment Group
  other name: Citicoline 1000mg
  intervention type: Other
  intervention name: Placebo
  description: Participants with MCI will receive a placebo supplement. Subjective sleep measures will be measured via the Pittsburgh Sleep Quality Index (for measurement of sleep quality) and Epworth Sleepiness Scale (for measurement of sleepiness). Cognition will be measured by Rey Auditory Verbal Learning Test (RAVLT), Trail Making Test (TMT) Parts A & B, and the Montreal Cognitive Assessment (MOCA). Participants will complete all questionnaires at baseline and at follow-up at 3 months. Participants will undergo a blood draw of approximately 20 ml at baseline and at follow-up.
  arm group label: Placebo
  criteria: 
  gender: All
  minimum age: 60 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Victoria Pak, PhD, MS, MTR
  role: Principal Investigator
  affiliation: Emory University
  last name: Victoria Pak, PhD, MS, MTR
  phone: 470-296-0081
  email: victoria.m.pak@emory.edu
  facility: 
  facility: 
  country: United States
  responsible party type: Principal Investigator
  investigator affiliation: Emory University
  investigator full name: Victoria Pak
  investigator title: Assistant Professor
  mesh term: Alzheimer Disease
  mesh term: Cognitive Dysfunction
  mesh term: Cytidine Diphosphate Choline
  sharing ipd: Yes
  ipd description: The research team will share deidentified data in accordance with the NIH Data Sharing Policy to share research resources (biological samples and finalized data). Deidentified data and deidentified biological samples will be stored and shared with other institutions or companies as approved by a Scientific Review Committee and in accordance with all applicable regulations.
  ipd time frame: Anticipated data availability will be at the conclusion of this study on 7/1/25.
  ipd access criteria: Data will be shared with the Aging Research Biobank. The data generated in this study will be housed in the Aging Research Biobank. The database can be found at the following link: agingresearchbiobank.nia.nih.gov
  ipd url: https://agingresearchbiobank.nia.nih.gov