<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/NCT01715727</url>
  </required_header>
  <id_info>
    <org_study_id>100-3761A3</org_study_id>
    <nct_id>NCT01715727</nct_id>
  </id_info>
  <brief_title>Diagnosis of Parkinson's Disease Using Diffusion Magnetic Resonance Imaging</brief_title>
  <official_title>Diagnosis of Parkinson's Disease Using Diffusion Magnetic Resonance Imaging</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Wang . Jiun-Jie</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Science Council, Taiwan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Chang Gung Memorial Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The hypothesis of the study is that the dopaminergic cell death located in the basal ganglia&#xD;
      of the brain in patients with Parkinson's Disease can be detected by diffusion Magnetic&#xD;
      Resonance Imaging, specifically by diffusion kurtosis imaging. The preliminary result was&#xD;
      published in Radiology 2011. The current study proposed to investigate the following issues:&#xD;
&#xD;
        -  validation of diagnostic sensitivity and specificity&#xD;
&#xD;
        -  differential diagnosis capability between PD and PD+ syndrome&#xD;
&#xD;
        -  prognosis capability&#xD;
&#xD;
      In the first year, patients with Parkinson's disease will be recruited from the outpatient&#xD;
      clinics of movement disorders in ChangGung memorial hospital Linkou, Taiwan. The diffusion&#xD;
      parameters in basal ganglia will be compared with a group of healthy controls. In the second&#xD;
      year, patients with progressive supranuclear palsy and patients with multiple system atrophy&#xD;
      will be recruited for assessment of differential diagnosis. The patients with Parkinson's&#xD;
      Disease will return for assessment of disease severity and in the third year, for the outcome&#xD;
      evaluation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Currently there existed no specific diagnostic test of Parkinson's Disease. Accurate&#xD;
      diagnosis is of great interest because of the reduction in health cost and disease&#xD;
      co-morbidity, improvement in effective treatment course and avoidance of un-necessary&#xD;
      intervention. Our preliminary result showed superior performance from diffusion kurtosis&#xD;
      imaging, a new development in MRI since 2007, on the diagnosis of Parkinson's Disease when&#xD;
      compared to conventional diffusion MRI. The study proposes to validate the diagnostic value&#xD;
      of diffusion kurtosis in major basal ganglia regions using a cross-sectional study and to&#xD;
      assess the prognostic value through 3-year longitudinal follow-up. Furthermore, the iron&#xD;
      content as well as global white matter involvement in both PD and PD plus syndrome patients&#xD;
      will be assessed. The difference in MRI information between PD and PD plus syndrome patients&#xD;
      will then be addressed in a comprehensive manner.&#xD;
&#xD;
      One hundred and twelve patients with Parkinson's Disease will be recruited in the first year&#xD;
      and followed up for 3 years. Another 112 healthy controls will be included. This is to&#xD;
      validate the diagnosis and assess the prognosis. Another 30 patients with Parkinson's&#xD;
      Disease, 15 patients with progressive supranuclear palsy and 15 patients with multiple system&#xD;
      atrophy will be recruited in the 2nd year for differential diagnosis. The imaging protocol&#xD;
      will include both diffusion tensor and diffusion kurtosis imaging. Susceptibility weighted&#xD;
      imaging will be included for iron content estimation. The targeted anatomy will include&#xD;
      regional changes in basal ganglia, midbrain as well as thalamus, and global white matter&#xD;
      changes using tract based spatial statistics. The statistical analysis will use receiver&#xD;
      operative characteristics to assess the diagnostic performance, Spearman's ranked correlation&#xD;
      for correlation with disease severity and net reclassification improvement for differential&#xD;
      diagnosis. The prognostic value will be determined by the decline rate and the quality of&#xD;
      life.&#xD;
&#xD;
      The end points of the project are to differentiate patients of PD from PD plus syndrome, and&#xD;
      to predict the clinical outcomes using diffusion MRI. Patent application will be filed in the&#xD;
      first year. The analysis of medical device software and software life cycle processes and the&#xD;
      evaluation of risk management to medical devices will be filed at the end of the third year.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>July 2012</start_date>
  <completion_date type="Actual">September 2015</completion_date>
  <primary_completion_date type="Actual">September 2015</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Case-Control</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>differential diagnosis</measure>
    <time_frame>end of the second year</time_frame>
    <description>To differentiate patient of PD from PD + using diffusion MRI</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>prognosis</measure>
    <time_frame>end of the third year</time_frame>
    <description>To predict the outcome of patient with PD using the diffusion MRI at baseline</description>
  </secondary_outcome>
  <number_of_groups>5</number_of_groups>
  <enrollment type="Actual">284</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Parkinson's Disease for follow-up</arm_group_label>
    <description>Patients should fulfill the National Institute of Neurological Disorders and Stroke in USA ( NINDS ) Diagnostic Criteria for Parkinson Disease(37) for &quot;probable&quot; PD, except for the age of onset.&#xD;
Able to tolerate the disability during the &quot;drug-off&quot; state, at least for 12 hours.&#xD;
Able to understand and provide signed informed consent.&#xD;
Early to moderate stage defined as Hohen and Yahr stage 1-3,</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Parkinsons&quot;s Disease with severity match</arm_group_label>
    <description>Parkinsons&quot;s Disease with severity match: 30 subjects&#xD;
Patients should fulfill the National Institute of Neurological Disorders and Stroke in USA ( NINDS ) Diagnostic Criteria for Parkinson Disease(37) for &quot;probable&quot; PD, except for the age of onset.&#xD;
Able to tolerate the disability during the &quot;drug-off&quot; state, at least for 12 hours.&#xD;
Able to understand and provide signed informed consent.&#xD;
Severity matched with PSP (subjects = 15)/MSA (subjects= 15), the severity was judged by Hohen and Yahr stage</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy age matched controls</arm_group_label>
    <description>Healthy age matched controls: subjects = 112&#xD;
Healthy subjects without a clinically significant abnormal laboratory values, and/or clinically significant or unstable medical or psychiatric illness.&#xD;
Able to understand and provide signed informed consent.&#xD;
Age range and gender matched with Parkinsons&quot;s Disease for follow up.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Parkinson Plus Syndrome Group M</arm_group_label>
    <description>MSA Patients should fulfill the NINDS Consensus statement for the clinical diagnosis of probable MSA&#xD;
Able to tolerate the disability during the &quot;drug-off&quot; state, at least for 12 hours.&#xD;
Able to understand and provide signed informed consent</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Parkinson Plus Syndrome Group P</arm_group_label>
    <description>PSP Patients should fulfill the NINDS-SPSP and Litvan criteria(4) for probable PSP&#xD;
Able to tolerate the disability during the &quot;drug-off&quot; state, at least for 12 hours.&#xD;
Able to understand and provide signed informed consent.</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        Patients will be recruited from the movement disorder clinics in ChangGung memorial&#xD;
        hospital LinKou. The healthy control will be recruited from the local community in northern&#xD;
        Taiwan.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Parkinsons&quot;s Disease for follow up: 112 subjects&#xD;
&#xD;
          1. Patients should fulfill the National Institute of Neurological Disorders and Stroke in&#xD;
             USA ( NINDS ) Diagnostic Criteria for Parkinson Disease(37) for &quot;probable&quot; PD, except&#xD;
             for the age of onset.&#xD;
&#xD;
          2. Able to tolerate the disability during the &quot;drug-off&quot; state, at least for 12 hours.&#xD;
&#xD;
          3. Able to understand and provide signed informed consent. 4. Early to moderate stage&#xD;
             defined as Hohen and Yahr stage 1-3, subjects = 100&#xD;
&#xD;
        Parkinsons&quot;s Disease with severity match: 30 subjects&#xD;
&#xD;
          1. Patients should fulfill the National Institute of Neurological Disorders and Stroke in&#xD;
             USA ( NINDS ) Diagnostic Criteria for Parkinson Disease(37) for &quot;probable&quot; PD, except&#xD;
             for the age of onset.&#xD;
&#xD;
          2. Able to tolerate the disability during the &quot;drug-off&quot; state, at least for 12 hours.&#xD;
&#xD;
          3. Able to understand and provide signed informed consent. 4. Severity matched with PSP&#xD;
             (subjects = 15)/MSA (subjects= 15), the severity was judged by Hohen and Yahr stage&#xD;
&#xD;
        Healthy age matched controls: subjects = 112 1. Healthy subjects without a clinically&#xD;
        significant abnormal laboratory values, and/or clinically significant or unstable medical&#xD;
        or psychiatric illness. 2. Able to understand and provide signed informed consent. 3. Age&#xD;
        range and gender matched with Parkinsons&quot;s Disease for follow up.&#xD;
&#xD;
        Parkinson Plus Syndrome Group M ( Multi System Atrophy, subjects = 15 ):&#xD;
&#xD;
        1. MSA Patients should fulfill the NINDS Consensus statement for the clinical diagnosis of&#xD;
        probable MSA(38) 2. Able to tolerate the disability during the &quot;drug-off&quot; state, at least&#xD;
        for 12 hours. 3. Able to understand and provide signed informed consent 2012/04/20 第二版 14&#xD;
&#xD;
        Parkinson Plus Syndrome Group P (Progressive Supranuclear Palsy, subjects = 15):&#xD;
&#xD;
          1. PSP Patients should fulfill the NINDS-SPSP and Litvan criteria(4) for probable PSP&#xD;
&#xD;
          2. Able to tolerate the disability during the &quot;drug-off&quot; state, at least for 12 hours.&#xD;
&#xD;
          3. Able to understand and provide signed informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        The following exclusion criteria apply to all groups.&#xD;
&#xD;
          1. Cardiac pacemaker implantation.&#xD;
&#xD;
          2. Implantation of intracranial metal device.&#xD;
&#xD;
          3. Significant major systemic disease, such as renal failure, heart failure, stroke,&#xD;
             AMI/unstable angina, poor controlled diabetes mellitus, poor controlled hypertension.&#xD;
&#xD;
          4. Pregnant or breast feeding women.&#xD;
&#xD;
          5. Moderate to severer dementia.&#xD;
&#xD;
          6. Severe dyskinesia&#xD;
&#xD;
          7. Any documented abnormality of brain in the brain by MRI and 18FDG PET studies, which&#xD;
             might contribute to the cognitive function, such as hydrocephalus or encephalomalacia,&#xD;
             will be excluded. Mild cortical atrophy will be allowed.&#xD;
&#xD;
          8. History of intracranial operation, including thalamotomy, pallidotomy, and/or deep&#xD;
             brain stimulation.&#xD;
&#xD;
          9. Significant physical disorder or neuropsychiatric disorder.&#xD;
&#xD;
         10. Except the medication for parkinsonism and related symptoms, subjects who received any&#xD;
             medication that can pass the blood-brain barrier will be excluded.&#xD;
&#xD;
         11. Except the medication for parkinsonism and related symptoms, subjects who chronically&#xD;
             take any drug for more than 10 years will be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>40 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jiun-Jie Wang, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>ChangGung University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>ChangGung Memorial Hospital, Linkou</name>
      <address>
        <city>TaoYuan county</city>
        <zip>333</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <reference>
    <citation>Wang JJ, Lin WY, Lu CS, Weng YH, Ng SH, Wang CH, Liu HL, Hsieh RH, Wan YL, Wai YY. Parkinson disease: diagnostic utility of diffusion kurtosis imaging. Radiology. 2011 Oct;261(1):210-7. doi: 10.1148/radiol.11102277. Epub 2011 Jul 19.</citation>
    <PMID>21771952</PMID>
  </reference>
  <verification_date>August 2016</verification_date>
  <study_first_submitted>October 25, 2012</study_first_submitted>
  <study_first_submitted_qc>October 25, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 29, 2012</study_first_posted>
  <last_update_submitted>August 3, 2016</last_update_submitted>
  <last_update_submitted_qc>August 3, 2016</last_update_submitted_qc>
  <last_update_posted type="Estimate">August 4, 2016</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Chang Gung Memorial Hospital</investigator_affiliation>
    <investigator_full_name>Wang . Jiun-Jie</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>diffusion kurtosis imaging</keyword>
  <keyword>parkinson disease</keyword>
  <keyword>parkinsonism</keyword>
  <keyword>diagnosis</keyword>
  <keyword>differential diagnosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <!-- 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/NCT01715727
org study id: 100-3761A3
nct id: NCT01715727
lead sponsor: 
collaborator: 
has dmc: Yes
The hypothesis of the study is that the dopaminergic cell death located in the basal ganglia
      of the brain in patients with Parkinson's Disease can be detected by diffusion Magnetic
      Resonance Imaging, specifically by diffusion kurtosis imaging. The preliminary result was
      published in Radiology 2011. The current study proposed to investigate the following issues:

        -  validation of diagnostic sensitivity and specificity

        -  differential diagnosis capability between PD and PD+ syndrome

        -  prognosis capability

      In the first year, patients with Parkinson's disease will be recruited from the outpatient
      clinics of movement disorders in ChangGung memorial hospital Linkou, Taiwan. The diffusion
      parameters in basal ganglia will be compared with a group of healthy controls. In the second
      year, patients with progressive supranuclear palsy and patients with multiple system atrophy
      will be recruited for assessment of differential diagnosis. The patients with Parkinson's
      Disease will return for assessment of disease severity and in the third year, for the outcome
      evaluation.
Currently there existed no specific diagnostic test of Parkinson's Disease. Accurate
      diagnosis is of great interest because of the reduction in health cost and disease
      co-morbidity, improvement in effective treatment course and avoidance of un-necessary
      intervention. Our preliminary result showed superior performance from diffusion kurtosis
      imaging, a new development in MRI since 2007, on the diagnosis of Parkinson's Disease when
      compared to conventional diffusion MRI. The study proposes to validate the diagnostic value
      of diffusion kurtosis in major basal ganglia regions using a cross-sectional study and to
      assess the prognostic value through 3-year longitudinal follow-up. Furthermore, the iron
      content as well as global white matter involvement in both PD and PD plus syndrome patients
      will be assessed. The difference in MRI information between PD and PD plus syndrome patients
      will then be addressed in a comprehensive manner.

      One hundred and twelve patients with Parkinson's Disease will be recruited in the first year
      and followed up for 3 years. Another 112 healthy controls will be included. This is to
      validate the diagnosis and assess the prognosis. Another 30 patients with Parkinson's
      Disease, 15 patients with progressive supranuclear palsy and 15 patients with multiple system
      atrophy will be recruited in the 2nd year for differential diagnosis. The imaging protocol
      will include both diffusion tensor and diffusion kurtosis imaging. Susceptibility weighted
      imaging will be included for iron content estimation. The targeted anatomy will include
      regional changes in basal ganglia, midbrain as well as thalamus, and global white matter
      changes using tract based spatial statistics. The statistical analysis will use receiver
      operative characteristics to assess the diagnostic performance, Spearman's ranked correlation
      for correlation with disease severity and net reclassification improvement for differential
      diagnosis. The prognostic value will be determined by the decline rate and the quality of
      life.

      The end points of the project are to differentiate patients of PD from PD plus syndrome, and
      to predict the clinical outcomes using diffusion MRI. Patent application will be filed in the
      first year. The analysis of medical device software and software life cycle processes and the
      evaluation of risk management to medical devices will be filed at the end of the third year.
observational model: Case-Control
time perspective: Prospective
measure: differential diagnosis
time frame: end of the second year
description: To differentiate patient of PD from PD + using diffusion MRI
measure: prognosis
time frame: end of the third year
description: To predict the outcome of patient with PD using the diffusion MRI at baseline
arm group label: Parkinson's Disease for follow-up
description: Patients should fulfill the National Institute of Neurological Disorders and Stroke in USA ( NINDS ) Diagnostic Criteria for Parkinson Disease(37) for "probable" PD, except for the age of onset.
Able to tolerate the disability during the "drug-off" state, at least for 12 hours.
Able to understand and provide signed informed consent.
Early to moderate stage defined as Hohen and Yahr stage 1-3,
arm group label: Parkinsons"s Disease with severity match
description: Parkinsons"s Disease with severity match: 30 subjects
Patients should fulfill the National Institute of Neurological Disorders and Stroke in USA ( NINDS ) Diagnostic Criteria for Parkinson Disease(37) for "probable" PD, except for the age of onset.
Able to tolerate the disability during the "drug-off" state, at least for 12 hours.
Able to understand and provide signed informed consent.
Severity matched with PSP (subjects = 15)/MSA (subjects= 15), the severity was judged by Hohen and Yahr stage
arm group label: Healthy age matched controls
description: Healthy age matched controls: subjects = 112
Healthy subjects without a clinically significant abnormal laboratory values, and/or clinically significant or unstable medical or psychiatric illness.
Able to understand and provide signed informed consent.
Age range and gender matched with Parkinsons"s Disease for follow up.
arm group label: Parkinson Plus Syndrome Group M
description: MSA Patients should fulfill the NINDS Consensus statement for the clinical diagnosis of probable MSA
Able to tolerate the disability during the "drug-off" state, at least for 12 hours.
Able to understand and provide signed informed consent
arm group label: Parkinson Plus Syndrome Group P
description: PSP Patients should fulfill the NINDS-SPSP and Litvan criteria(4) for probable PSP
Able to tolerate the disability during the "drug-off" state, at least for 12 hours.
Able to understand and provide signed informed consent.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 40 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Jiun-Jie Wang, PhD
role: Principal Investigator
affiliation: ChangGung University
facility: 
country: Taiwan
citation: Wang JJ, Lin WY, Lu CS, Weng YH, Ng SH, Wang CH, Liu HL, Hsieh RH, Wan YL, Wai YY. Parkinson disease: diagnostic utility of diffusion kurtosis imaging. Radiology. 2011 Oct;261(1):210-7. doi: 10.1148/radiol.11102277. Epub 2011 Jul 19.
PMID: 21771952
responsible party type: Sponsor-Investigator
investigator affiliation: Chang Gung Memorial Hospital
investigator full name: Wang . Jiun-Jie
investigator title: Associate Professor
mesh term: Parkinson Disease