<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/NCT02984137</url>
  </required_header>
  <id_info>
    <org_study_id>16-2013-101</org_study_id>
    <nct_id>NCT02984137</nct_id>
  </id_info>
  <brief_title>Prospective Neuroimaging Investigation of Idiopathic REM Sleep Behavior Disorder</brief_title>
  <official_title>A Prospective Longitudinal Neuroimaging and Biomarker Cohort Study in Idiopathic Rapid Eye Movement(REM) Sleep Behavior Disorder</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Seoul National University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>SMG-SNU Boramae Medical Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Seoul National University Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a prospective cohort study to evaluate degenerative changes in the brain by&#xD;
      performing functional imaging analysis in patients with RBD and its correlations with&#xD;
      clinical symptoms and dopaminergic degeneration. This study also evaluates cognitive changes&#xD;
      with functional imaging measures and olfactory and other premotor symptoms of Lewy body&#xD;
      disease. This study also collects gene extracts and sera to develop a biomarker for early&#xD;
      detection of neurodegeneration.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will include 3 groups in relation with RBD: idiopathic RBD (iRBD), PD- RBD, normal&#xD;
      controls without RBD. In all groups, neurological examinations, olfactory testings, nonmotor&#xD;
      symptoms evaluations, neuropsychological evaluations (detailed outcomes are in the outcome&#xD;
      section) will be performed at baseline evaluation after enrollment. Image data will be&#xD;
      obtained on following modalities: brain magnetic resonance imaging (MRI),&#xD;
      18F-N-ω-fluoropropyl- 2β-carbomethoxy- 3β-(4-iodophenyl) nortropane ([18F]FP-CIT) positron&#xD;
      emission tomography (PET), and 18F-fludeoxyglucose([18F]FDG) PET.&#xD;
&#xD;
      To assess progression toward Lewy body disorders, patients in iRBD group will be evaluated at&#xD;
      2, and 4 years of follow-up visit. Clinical, neuropsychological tests, brain MRI, and two PET&#xD;
      scans will be administered. After 4 years, patients who are willing to participate will be&#xD;
      additionally followed-up yearly as a routine clinical visit with clinical and neurological&#xD;
      examinations until obvious signs of Lewy body diseases will develop.&#xD;
&#xD;
      In PD-RBD group, patients will be evaluated at 3-year follow-up period amongst days of&#xD;
      routine clinic visits with administering clinical and neuropsychological tests.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 2013</start_date>
  <completion_date type="Actual">August 2018</completion_date>
  <primary_completion_date type="Actual">August 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Diagnostic</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Frequency of development of Lewy body diseases</measure>
    <time_frame>up to 4-years follow-up</time_frame>
    <description>idiopathic RBD group only</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Parkinsonian motor symptoms score change measured by the unified Parkinson's disease rating scale (MDS-UPDRS)</measure>
    <time_frame>from baseline to 2-years and 4-years follow-up (iRBD group), to 3-years follow-up (PD-RBD group)</time_frame>
    <description>descriptive, intragroup analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nonmotor symptoms profile change assessed by a combined evaluatin using the non-motor symptom scale and part I of the MDS-UPDRS</measure>
    <time_frame>from baseline to 2-years and 4-years follow-up (iRBD group), to 3-years follow-up (PD-RBD group)</time_frame>
    <description>descriptive, intragroup analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Cognitive change measured by the neuropsychological test battery</measure>
    <time_frame>from baseline to 2-years ad 4-years follow-up (iRBD group), to 3-years follow-up (PD-RBD group)</time_frame>
    <description>descriptive, intragroup analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degenerative brain changes predicted by MRI (diffusion tensor analysis and volumetry)</measure>
    <time_frame>from baseline to 2-years and 4-years follow-up (iRBD group only)</time_frame>
    <description>descriptive, intragroup analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional network changes predicted by the resting-state functional MRI</measure>
    <time_frame>from baseline to 2-years and 4-years follow-up (iRBD group only)</time_frame>
    <description>descriptive, intragroup analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Degenerative brain changes predicted by [18F]FP-CIT PET</measure>
    <time_frame>from baseline to 2-years and 4-years follow-up (iRBD group only)</time_frame>
    <description>descriptive, intragroup analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Functional network changes predicted by [18F]FDG PET</measure>
    <time_frame>from baseline to 2-years and 4-years follow-up (iRBD group only)</time_frame>
    <description>descriptive, intragroup analysis</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">80</enrollment>
  <condition>Parkinson Disease</condition>
  <condition>REM Sleep Behavior Disorder</condition>
  <arm_group>
    <arm_group_label>idiopathic RBD group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>A group of patients diagnosed as idiopathic RBD that is confirmed by polysomnography. Interventions as testing, evaluation, samplings at baseline, then repeat at 2 years and 4 years of prospective follow-up. thereafter only clinical observations until Lewy body disease is diagnosed.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>incident PD group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>A group of patients who are newly diagnosed as Parkinson's disease, and never been treated with prolonged history of probable RBD. Interventions as testing, evaluation, sampling at baseline and then evaluations only at 3 year follow-up after anti-parkinsonian treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Control group includes elderly controls without neurodegerative diseases examined by neurologists. Interventions as testing, evaluation, sampling at baseline only.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>testing, evaluation, sampling</intervention_name>
    <description>neuroimaging biomarkers using positron emission tomography and magnetic resonance imaging, and evaluation of neurological &amp; neurocognitive status by using a predefined neuropsychological assessment battery.</description>
    <arm_group_label>Control</arm_group_label>
    <arm_group_label>idiopathic RBD group</arm_group_label>
    <arm_group_label>incident PD group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        iRBD group:&#xD;
&#xD;
          -  A diagnosis of RBD according to the international classification of sleep disorders-2&#xD;
             (ICSD-2) criteria&#xD;
&#xD;
          -  No current neurological diseases related with RBD&#xD;
&#xD;
          -  Male or female aged from 30 to 80 years old at screening&#xD;
&#xD;
          -  Subject enrolled voluntarily and understood the contents of the study&#xD;
&#xD;
        PD group:&#xD;
&#xD;
          -  A diagnosis of PD according to the UK Brain Bank Diagnostic Criteria&#xD;
&#xD;
          -  A diagnosis of RBD according to the international classification of sleep disorders-2&#xD;
             (ICSD-2) criteria&#xD;
&#xD;
          -  Male or female aged from 30 to 80 years old at screening&#xD;
&#xD;
          -  Subject enrolled voluntarily and understood the contents of the study&#xD;
&#xD;
        Control group:&#xD;
&#xD;
          -  No current neurological or psychiatric diseases related with RBD&#xD;
&#xD;
          -  Male or female aged from 30 to 80 years old at screening&#xD;
&#xD;
          -  Age and sex matched with those of subjects in iRBD group&#xD;
&#xD;
          -  Subject enrolled voluntarily and understood the contents of the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically significant cognitive decline unable to follow the study (Mini-mental state&#xD;
             examination [MMSE] score less than 20)&#xD;
&#xD;
          -  History of psychiatric illnesses (ex. depression)&#xD;
&#xD;
          -  Unable to walk and cooperate to the examination&#xD;
&#xD;
          -  Unable to take magnetic resonance imaging or positron emission tomography&#xD;
&#xD;
          -  Existence of illness or problems which makes difficult to be enrolled to the study&#xD;
             judged by clinicians&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jee-Young Lee, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>SMG-SNU Boramae Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>SMG-SNU Boramae Medical Center</name>
      <address>
        <city>Seoul</city>
        <country>Korea, Republic of</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Korea, Republic of</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>November 30, 2016</study_first_submitted>
  <study_first_submitted_qc>December 5, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">December 6, 2016</study_first_posted>
  <last_update_submitted>March 17, 2020</last_update_submitted>
  <last_update_submitted_qc>March 17, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Seoul National University Hospital</investigator_affiliation>
    <investigator_full_name>Jee-Young Lee</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Lewy body disease</keyword>
  <keyword>REM Sleep Behavior Disorder</keyword>
  <keyword>Parkinson disease</keyword>
  <keyword>Imaging</keyword>
  <keyword>Bio-markers</keyword>
  <keyword>Prospective cohort</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>REM Sleep Behavior Disorder</mesh_term>
    <mesh_term>Mental Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT02984137
org study id: 16-2013-101
nct id: NCT02984137
lead sponsor: 
collaborator: 
has dmc: Yes
This is a prospective cohort study to evaluate degenerative changes in the brain by
      performing functional imaging analysis in patients with RBD and its correlations with
      clinical symptoms and dopaminergic degeneration. This study also evaluates cognitive changes
      with functional imaging measures and olfactory and other premotor symptoms of Lewy body
      disease. This study also collects gene extracts and sera to develop a biomarker for early
      detection of neurodegeneration.
This study will include 3 groups in relation with RBD: idiopathic RBD (iRBD), PD- RBD, normal
      controls without RBD. In all groups, neurological examinations, olfactory testings, nonmotor
      symptoms evaluations, neuropsychological evaluations (detailed outcomes are in the outcome
      section) will be performed at baseline evaluation after enrollment. Image data will be
      obtained on following modalities: brain magnetic resonance imaging (MRI),
      18F-N-ω-fluoropropyl- 2β-carbomethoxy- 3β-(4-iodophenyl) nortropane ([18F]FP-CIT) positron
      emission tomography (PET), and 18F-fludeoxyglucose([18F]FDG) PET.

      To assess progression toward Lewy body disorders, patients in iRBD group will be evaluated at
      2, and 4 years of follow-up visit. Clinical, neuropsychological tests, brain MRI, and two PET
      scans will be administered. After 4 years, patients who are willing to participate will be
      additionally followed-up yearly as a routine clinical visit with clinical and neurological
      examinations until obvious signs of Lewy body diseases will develop.

      In PD-RBD group, patients will be evaluated at 3-year follow-up period amongst days of
      routine clinic visits with administering clinical and neuropsychological tests.
allocation: Non-Randomized
intervention model: Single Group Assignment
primary purpose: Diagnostic
masking: Single (Outcomes Assessor)
measure: Frequency of development of Lewy body diseases
time frame: up to 4-years follow-up
description: idiopathic RBD group only
measure: Parkinsonian motor symptoms score change measured by the unified Parkinson's disease rating scale (MDS-UPDRS)
time frame: from baseline to 2-years and 4-years follow-up (iRBD group), to 3-years follow-up (PD-RBD group)
description: descriptive, intragroup analysis
measure: Nonmotor symptoms profile change assessed by a combined evaluatin using the non-motor symptom scale and part I of the MDS-UPDRS
time frame: from baseline to 2-years and 4-years follow-up (iRBD group), to 3-years follow-up (PD-RBD group)
description: descriptive, intragroup analysis
measure: Cognitive change measured by the neuropsychological test battery
time frame: from baseline to 2-years ad 4-years follow-up (iRBD group), to 3-years follow-up (PD-RBD group)
description: descriptive, intragroup analysis
measure: Degenerative brain changes predicted by MRI (diffusion tensor analysis and volumetry)
time frame: from baseline to 2-years and 4-years follow-up (iRBD group only)
description: descriptive, intragroup analysis
measure: Functional network changes predicted by the resting-state functional MRI
time frame: from baseline to 2-years and 4-years follow-up (iRBD group only)
description: descriptive, intragroup analysis
measure: Degenerative brain changes predicted by [18F]FP-CIT PET
time frame: from baseline to 2-years and 4-years follow-up (iRBD group only)
description: descriptive, intragroup analysis
measure: Functional network changes predicted by [18F]FDG PET
time frame: from baseline to 2-years and 4-years follow-up (iRBD group only)
description: descriptive, intragroup analysis
arm group label: idiopathic RBD group
arm group type: Experimental
description: A group of patients diagnosed as idiopathic RBD that is confirmed by polysomnography. Interventions as testing, evaluation, samplings at baseline, then repeat at 2 years and 4 years of prospective follow-up. thereafter only clinical observations until Lewy body disease is diagnosed.
arm group label: incident PD group
arm group type: Active Comparator
description: A group of patients who are newly diagnosed as Parkinson's disease, and never been treated with prolonged history of probable RBD. Interventions as testing, evaluation, sampling at baseline and then evaluations only at 3 year follow-up after anti-parkinsonian treatment.
arm group label: Control
arm group type: Placebo Comparator
description: Control group includes elderly controls without neurodegerative diseases examined by neurologists. Interventions as testing, evaluation, sampling at baseline only.
intervention type: Other
intervention name: testing, evaluation, sampling
description: neuroimaging biomarkers using positron emission tomography and magnetic resonance imaging, and evaluation of neurological & neurocognitive status by using a predefined neuropsychological assessment battery.
arm group label: Control
arm group label: idiopathic RBD group
arm group label: incident PD group
criteria: 
gender: All
minimum age: 30 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jee-Young Lee, MD, PhD
role: Principal Investigator
affiliation: SMG-SNU Boramae Medical Center
facility: 
country: Korea, Republic of
responsible party type: Principal Investigator
investigator affiliation: Seoul National University Hospital
investigator full name: Jee-Young Lee
investigator title: Associate Professor
mesh term: Parkinson Disease
mesh term: REM Sleep Behavior Disorder
mesh term: Mental Disorders
sharing ipd: Undecided