<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/NCT04472325</url>
  </required_header>
  <id_info>
    <org_study_id>106WFD2650309</org_study_id>
    <nct_id>NCT04472325</nct_id>
  </id_info>
  <brief_title>The Differential Diagnosis and Prognosis of Idiopathic and Atypical Parkinson Disease by Using Diffusion MRI</brief_title>
  <official_title>The Differential Diagnosis and Prognosis of Idiopathic and Atypical Parkinson Disease by Using Diffusion MRI</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chang Gung Memorial Hospital</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 hypothesis is that the differential extent of microstructural damages in the affected&#xD;
      brain regions can be specific to the disease of interest and could reflect the clinical&#xD;
      severity. Therefore, we propose that the whole brain parcellation of diffusion MRI can be&#xD;
      used to improve the diagnosis and prediction of clinical outcomes in Parkinson's Disease.&#xD;
&#xD;
        1. A regression model between clinical severity and two-year clinical outcomes and&#xD;
           diffusion properties from multiple parcellated regions will be developed.&#xD;
&#xD;
        2. Blind validation will be performed.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Parkinson's disease (PD) is a common progressive neurodegenerative disorder characterized by&#xD;
      resting tremor, bradykinesia, restricted mobility, and postural instability. Early diagnosis&#xD;
      of PD would be paramount for further treatment and prognosis. The most common&#xD;
      neurodegenerative parkinsonian syndrome is known as Parkinson's disease (PD) or idiopathic&#xD;
      Parkinson syndrome, if it occurs sporadically (not familial) and its lead clinical symptom is&#xD;
      a movement disorder after brainstem-predominant α-synuclein deposition. To distinguish them&#xD;
      from Parkinson's disease, other sporadic entities have been named atypical parkinsonian&#xD;
      syndromes or atypical parkinsonism. The present review article describes current standards&#xD;
      for the diagnosis and treatment of the most important disease entities in this latter group:&#xD;
      dementia with Lewy bodies (DLB), multiple system atrophy (MSA), progressive supranuclear&#xD;
      palsy (PSP), and corticobasal degeneration (CBD).&#xD;
&#xD;
      PD is diagnosed mainly by neurologists, based on clinical symptoms. However, there are no&#xD;
      objective criteria available for their diagnosis. Although magnetic resonance imaging (MRI)&#xD;
      is often employed in conjunction with clinical judgment, the images are mostly used to&#xD;
      eliminate other diseases, rather than to confirm the diagnosis. Other imaging methods, such&#xD;
      as Positron Emission Tomography or Computed Tomography, may help in the diagnosis of PD but&#xD;
      have harmful effects on the human body. MRI image of patients with Parkinson's disease is&#xD;
      usually normal. Previous studies have also indicated that brain-related areas, such as the&#xD;
      atrophy of basal ganglia, are not observed until a period of disease progression. However,&#xD;
      the shrinkage of brain tissue cannot be used as a criterion for the diagnosis of Parkinson's&#xD;
      disease, because many other diseases are accompanied by atrophy of brain tissue as well.&#xD;
      Furthermore, because human brain cells cannot regenerate, It is too late to diagnose or treat&#xD;
      when a large number of nerve cells are apoptotic. Since we expect the function of the&#xD;
      diseased cells to change first, therefore, if you can detect changes in the patient's brain&#xD;
      microenvironment, it is possible to achieve early detection of Parkinson's disease. Magnetic&#xD;
      resonance imaging can detect functional images and display functional changes, thus providing&#xD;
      an opportunity to detect abnormalities and diagnose diseases early. One of the key&#xD;
      technologies in the measurement of functional images is diffusion magnetic resonance imaging.&#xD;
&#xD;
      Diffusion MRI has been widely utilized to investigate the patterns of neural connectivity.&#xD;
      Mean diffusivity (MD) and the directionality (fractional anisotropy (FA)) have been studied&#xD;
      in epilepsy, multiple sclerosis, and noticeably in Parkinson's Disease. Owing to their&#xD;
      paramount pathogenetic role in Parkinson's disease, the basal ganglia in general and the&#xD;
      substantia nigra pars compacta, in particular, have been the subject of intense MRI&#xD;
      investigation.&#xD;
&#xD;
      The plan uses standard anatomic labeling (AAL) to perform whole-brain diffusion MRI to obtain&#xD;
      diffusion data for the whole brain parcellation. We will use statistical methods to identify&#xD;
      the areas affected by each PD's subtype, we will also identify areas that are likely to be&#xD;
      related to the severity of the disease, and then combine these areas for linear regression&#xD;
      analysis. We anticipate that diffusion magnetic resonance imaging can be used as a&#xD;
      differential diagnosis, as well as to define areas of high correlation with clinical&#xD;
      severity, and to be used for accurate disease prediction and future development, and to&#xD;
      provide physicians and patients with clinically important information.&#xD;
&#xD;
      The program uses diffusion magnetic resonance imaging to assess clinical status and prognosis&#xD;
      for Parkinson's disease. Our research goal is&#xD;
&#xD;
        1. Establish objective and clear imaging diagnostic criteria of diffusion MRI for&#xD;
           idiopathic and atypical Parkinson's disease.&#xD;
&#xD;
        2. Establish objective and clear clinical severity and the prognosis prediction mode of&#xD;
           diffusion MRI for idiopathic and atypical Parkinson's disease.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 1, 2017</start_date>
  <completion_date type="Actual">July 31, 2020</completion_date>
  <primary_completion_date type="Actual">August 1, 2018</primary_completion_date>
  <study_type>Observational [Patient Registry]</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>
  <target_duration>3 Years</target_duration>
  <primary_outcome>
    <measure>An objective image-based evidence for the diagnosis, differential diagnosis and prognosis of Parkinson's Disease</measure>
    <time_frame>end of the third year</time_frame>
    <description>The following will be measured for the diagnostic performance of diffusion MRI:&#xD;
Regression between cognitive performance and baseline diffusion MRI using Pearson correlation&#xD;
Leave one out cross validation</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>
  <secondary_outcome>
    <measure>prognosis</measure>
    <time_frame>end of the third year</time_frame>
    <description>Methods for evaluation of worsening cognitive function in neurodegenerative disease</description>
  </secondary_outcome>
  <secondary_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>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Imaging</measure>
    <time_frame>end of the third year</time_frame>
    <description>High-quality diffusion MRI and image data restoration</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Imaging</measure>
    <time_frame>end of the third year</time_frame>
    <description>High-quality diffusion MRI imaging standards, parcellation methods and image processing protocol</description>
  </secondary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">288</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Atypical Parkinson's Disease patients</arm_group_label>
    <description>This group consists of patients includes 35 patients with Progressive Supranuclear Paralysis (PSP), 35 patients with Multiple System Atrophy (MSA), and 35 patients with Cortico-Basal Degeneration (CBD).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Idiopathic Parkinson's Disease patients</arm_group_label>
    <description>This group consists of patients starting from 2012 to 2013 and includes 87 patients with typical Parkinson's Disease (PD)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Healthy volunteers</arm_group_label>
    <description>The 96 healthy volunteers should meet the following criteria:&#xD;
Between 50-80 years old&#xD;
Right-handed&#xD;
MMSE score greater than or equal to 26&#xD;
Able to understand study requirements and give informed consent</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        All subjects should meet the following criteria:&#xD;
&#xD;
          1. Between 50-80 years old&#xD;
&#xD;
          2. Right-handed&#xD;
&#xD;
          3. Able to understand study requirements and give informed consent&#xD;
&#xD;
          4. Agree to return for follow-up checks&#xD;
&#xD;
          5. Able to suspend intake of medication for at least 12 hours&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Cardiac pacemaker or defibrillator implantation Intracranial metal device implantation&#xD;
&#xD;
          -  Other major systemic diseases, such as renal failure, heart failure, stroke,&#xD;
             AMI/unstable angina, poorly controlled diabetes mellitus, poorly controlled&#xD;
             hypertension&#xD;
&#xD;
          -  Alcohol or drug abuse&#xD;
&#xD;
          -  Moderate to severe dementia&#xD;
&#xD;
          -  Severe movement disorders&#xD;
&#xD;
          -  Imaging data is similar to a nuclear medical examination, exclusion criteria is any&#xD;
             abnormality that may affect cognitive function as reflected in computer tomography or&#xD;
             MRI records, such as hydrocephalus or encephalitis. Mild cortical atrophy is&#xD;
             acceptable.&#xD;
&#xD;
          -  History of intracranial surgery including thalamotomy, pallidotomy, and/or deep brain&#xD;
             stimulation&#xD;
&#xD;
          -  Major physical or neuropsychiatric disorders&#xD;
&#xD;
          -  Structural abnormalities that may cause dementia, such as cortical infarction, tumour,&#xD;
             or subdural hematoma&#xD;
&#xD;
          -  Besides medication for Parkinson's Disease, taking other medication with substances&#xD;
             that can pass through the blood-brain barrier&#xD;
&#xD;
          -  Besides medication for Parkinson's Disease, taking other medication for more than 10&#xD;
             years&#xD;
&#xD;
          -  Treatments or concurrent illnesses other than Alzheimer's Disease that could interfere&#xD;
             with cognitive function&#xD;
&#xD;
          -  Meet the criteria for dementia (DSM-IV)&#xD;
&#xD;
          -  Head trauma with loss of consciousness greater than 10 minutes&#xD;
&#xD;
          -  Severe loss of sensation&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>50 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>ChangGung Memorial Hospital, Linkou</name>
      <address>
        <city>Taoyuan</city>
        <zip>333</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>August 2021</verification_date>
  <study_first_submitted>June 14, 2020</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 15, 2020</study_first_posted>
  <last_update_submitted>August 5, 2021</last_update_submitted>
  <last_update_submitted_qc>August 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">August 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Chang Gung Memorial Hospital</investigator_affiliation>
    <investigator_full_name>Wang . Jiun-Jie</investigator_full_name>
    <investigator_title>Study Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Magnetic Resonance Imaging</keyword>
  <keyword>Neurodegeneration disease</keyword>
  <keyword>Cognitive impairment</keyword>
  <keyword>Diagnosis</keyword>
  <keyword>Prognosis</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/NCT04472325
org study id: 106WFD2650309
nct id: NCT04472325
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The hypothesis is that the differential extent of microstructural damages in the affected
      brain regions can be specific to the disease of interest and could reflect the clinical
      severity. Therefore, we propose that the whole brain parcellation of diffusion MRI can be
      used to improve the diagnosis and prediction of clinical outcomes in Parkinson's Disease.

        1. A regression model between clinical severity and two-year clinical outcomes and
           diffusion properties from multiple parcellated regions will be developed.

        2. Blind validation will be performed.
Parkinson's disease (PD) is a common progressive neurodegenerative disorder characterized by
      resting tremor, bradykinesia, restricted mobility, and postural instability. Early diagnosis
      of PD would be paramount for further treatment and prognosis. The most common
      neurodegenerative parkinsonian syndrome is known as Parkinson's disease (PD) or idiopathic
      Parkinson syndrome, if it occurs sporadically (not familial) and its lead clinical symptom is
      a movement disorder after brainstem-predominant α-synuclein deposition. To distinguish them
      from Parkinson's disease, other sporadic entities have been named atypical parkinsonian
      syndromes or atypical parkinsonism. The present review article describes current standards
      for the diagnosis and treatment of the most important disease entities in this latter group:
      dementia with Lewy bodies (DLB), multiple system atrophy (MSA), progressive supranuclear
      palsy (PSP), and corticobasal degeneration (CBD).

      PD is diagnosed mainly by neurologists, based on clinical symptoms. However, there are no
      objective criteria available for their diagnosis. Although magnetic resonance imaging (MRI)
      is often employed in conjunction with clinical judgment, the images are mostly used to
      eliminate other diseases, rather than to confirm the diagnosis. Other imaging methods, such
      as Positron Emission Tomography or Computed Tomography, may help in the diagnosis of PD but
      have harmful effects on the human body. MRI image of patients with Parkinson's disease is
      usually normal. Previous studies have also indicated that brain-related areas, such as the
      atrophy of basal ganglia, are not observed until a period of disease progression. However,
      the shrinkage of brain tissue cannot be used as a criterion for the diagnosis of Parkinson's
      disease, because many other diseases are accompanied by atrophy of brain tissue as well.
      Furthermore, because human brain cells cannot regenerate, It is too late to diagnose or treat
      when a large number of nerve cells are apoptotic. Since we expect the function of the
      diseased cells to change first, therefore, if you can detect changes in the patient's brain
      microenvironment, it is possible to achieve early detection of Parkinson's disease. Magnetic
      resonance imaging can detect functional images and display functional changes, thus providing
      an opportunity to detect abnormalities and diagnose diseases early. One of the key
      technologies in the measurement of functional images is diffusion magnetic resonance imaging.

      Diffusion MRI has been widely utilized to investigate the patterns of neural connectivity.
      Mean diffusivity (MD) and the directionality (fractional anisotropy (FA)) have been studied
      in epilepsy, multiple sclerosis, and noticeably in Parkinson's Disease. Owing to their
      paramount pathogenetic role in Parkinson's disease, the basal ganglia in general and the
      substantia nigra pars compacta, in particular, have been the subject of intense MRI
      investigation.

      The plan uses standard anatomic labeling (AAL) to perform whole-brain diffusion MRI to obtain
      diffusion data for the whole brain parcellation. We will use statistical methods to identify
      the areas affected by each PD's subtype, we will also identify areas that are likely to be
      related to the severity of the disease, and then combine these areas for linear regression
      analysis. We anticipate that diffusion magnetic resonance imaging can be used as a
      differential diagnosis, as well as to define areas of high correlation with clinical
      severity, and to be used for accurate disease prediction and future development, and to
      provide physicians and patients with clinically important information.

      The program uses diffusion magnetic resonance imaging to assess clinical status and prognosis
      for Parkinson's disease. Our research goal is

        1. Establish objective and clear imaging diagnostic criteria of diffusion MRI for
           idiopathic and atypical Parkinson's disease.

        2. Establish objective and clear clinical severity and the prognosis prediction mode of
           diffusion MRI for idiopathic and atypical Parkinson's disease.
observational model: Case-Control
time perspective: Prospective
measure: An objective image-based evidence for the diagnosis, differential diagnosis and prognosis of Parkinson's Disease
time frame: end of the third year
description: The following will be measured for the diagnostic performance of diffusion MRI:
Regression between cognitive performance and baseline diffusion MRI using Pearson correlation
Leave one out cross validation
measure: prognosis
time frame: end of the third year
description: To predict the outcome of patient with PD using the diffusion MRI at baseline
measure: prognosis
time frame: end of the third year
description: Methods for evaluation of worsening cognitive function in neurodegenerative disease
measure: differential diagnosis
time frame: end of the second year
description: To differentiate patient of PD from PD + using diffusion MRI
measure: Imaging
time frame: end of the third year
description: High-quality diffusion MRI and image data restoration
measure: Imaging
time frame: end of the third year
description: High-quality diffusion MRI imaging standards, parcellation methods and image processing protocol
arm group label: Atypical Parkinson's Disease patients
description: This group consists of patients includes 35 patients with Progressive Supranuclear Paralysis (PSP), 35 patients with Multiple System Atrophy (MSA), and 35 patients with Cortico-Basal Degeneration (CBD).
arm group label: Idiopathic Parkinson's Disease patients
description: This group consists of patients starting from 2012 to 2013 and includes 87 patients with typical Parkinson's Disease (PD)
arm group label: Healthy volunteers
description: The 96 healthy volunteers should meet the following criteria:
Between 50-80 years old
Right-handed
MMSE score greater than or equal to 26
Able to understand study requirements and give informed consent
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 50 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: Taiwan
responsible party type: Principal Investigator
investigator affiliation: Chang Gung Memorial Hospital
investigator full name: Wang . Jiun-Jie
investigator title: Study Principal Investigator
mesh term: Parkinson Disease