<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/NCT03234478</url>
  </required_header>
  <id_info>
    <org_study_id>Pro2020000729</org_study_id>
    <secondary_id>1K23NS097625-01A1</secondary_id>
    <nct_id>NCT03234478</nct_id>
  </id_info>
  <brief_title>Parkinson Disease and DBS: Cognitive Effects in GBA Mutation Carriers</brief_title>
  <official_title>Parkinson Disease and DBS: Cognitive Effects in GBA Mutation Carriers</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rutgers, The State University of New Jersey</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Rutgers, The State University of New Jersey</source>
  <oversight_info>
    <has_dmc>No</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>
      Every year, approximately 9,000 Parkinson disease (PD) patients undergo deep brain stimulator&#xD;
      (DBS) placement into the subthalamic nucleus (STN-DBS). Studies suggest that PD patients with&#xD;
      mutations in the glucocerebrosidase (GBA) gene are at high risk for cognitive impairment and&#xD;
      approximately 10-17% of subjects undergoing DBS carry GBA mutations. There may be an&#xD;
      interaction between STN-DBS, which also impairs cognitive function, and GBA, resulting in&#xD;
      worsened cognitive function. This project will 1) determine the relationship between GBA&#xD;
      mutation status and post-operative STN-DBS cognitive function, 2) broaden genotype-phenotype&#xD;
      relationships of GBA mutation carriers and 3) provide scientific knowledge regarding the&#xD;
      longitudinal cognitive effects of DBS in GBA mutation carriers through repeated&#xD;
      neuropsychological testing.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Parkinson disease (PD) is a neurodegenerative disease affecting at least 1 million people in&#xD;
      the U.S. Each year, 9,000 PD patients undergo deep brain stimulator (DBS) placement into the&#xD;
      subthalamic nucleus (STN-DBS), the most commonly used basal ganglia target. Despite motor&#xD;
      improvement, up to 50% of patients have cognitive impairment after DBS. Cognitive impairment&#xD;
      is associated with a 2-3 fold increase in mortality, progression to dementia, and nursing&#xD;
      home placement. At present, subjects with cognitive impairment after DBS cannot be identified&#xD;
      pre-operatively and the effects of DBS on cognitive function are not fully understood. A&#xD;
      specific group of PD patients, carriers of mutations in the glucocerebrosidase (GBA) gene,&#xD;
      are at particularly high risk for cognitive impairment. PD-GBA mutation carriers have&#xD;
      dysfunction of the glucocerebrosidase (GCase) enzyme, resulting in more rapid accumulation&#xD;
      and spread of Lewy bodies compared with non-mutation carriers. Clinically, PD-GBA mutation&#xD;
      carriers have: (1) deficits in visual memory due to higher Lewy body burden in hippocampal&#xD;
      and medial temporal regions, and (2) faster progression to dementia secondary to diffuse&#xD;
      cortical Lewy body pathology. Approximately 10-17% of PD subjects with DBS carry GBA&#xD;
      mutations, indicating that a substantial portion of the DBS population may be susceptible to&#xD;
      cognitive problems. Importantly, STN-DBS itself can impair cognition through modulation of&#xD;
      the striato-anterior cingulate cortex circuit, resulting in impulsivity and more errors when&#xD;
      faced with tasks that rely on executive functions. Therefore, the central hypothesis is that&#xD;
      PD-GBA mutation carriers have greater global cognitive decline after STN-DBS compared with&#xD;
      PD-GBA mutation carriers without STN-DBS, and compared with non-mutation carriers with and&#xD;
      without STN-DBS. This is a critical area of research because if an association between GBA&#xD;
      and STN-DBS is detected, clinicians will be able to identify subjects at risk for worsened&#xD;
      cognitive dysfunction through genetic testing and prevent harm by: (1) recommending that&#xD;
      PD-GBA mutation carriers avoid STN-DBS, or (2) considering an alternative DBS target such as&#xD;
      the globus pallidus interna (GPi) that may have less cognitive side effects. The following&#xD;
      aims are proposed: Aim 1: Determine the longitudinal changes in global cognitive function in&#xD;
      PD-GBA mutation carriers and non-mutation carriers with and without STN-DBS; Aim 2: Determine&#xD;
      the specific pattern of cognitive dysfunction in PD-GBA mutation carriers and non-mutation&#xD;
      carriers with and without STN-DBS; Aim 3: Determine the differential effects of DBS on&#xD;
      cognitive function in the ON-stimulation state vs. OFF-stimulation state, comparing PD-GBA&#xD;
      mutation and non-mutation carriers.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Anticipated">June 30, 2024</completion_date>
  <primary_completion_date type="Anticipated">June 30, 2024</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Prospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Mattis Dementia Rating Scale</measure>
    <time_frame>2 years</time_frame>
    <description>scale to assess global cognition</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>NIH toolbox cognition battery</measure>
    <time_frame>1 year</time_frame>
    <description>iPAD based cognitive battery</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Neuro-QoL</measure>
    <time_frame>2 years</time_frame>
    <description>scale to assess quality of life</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PROMIS</measure>
    <time_frame>2 years</time_frame>
    <description>scale to assess quality of life</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Anticipated">262</enrollment>
  <condition>Parkinson</condition>
  <condition>Parkinson Disease</condition>
  <condition>Genetic Predisposition</condition>
  <condition>GBA Gene Mutation</condition>
  <condition>Cognitive Decline</condition>
  <arm_group>
    <arm_group_label>GBA mutation carriers without DBS</arm_group_label>
    <description>Parkinson's disease patients who have moderate to advanced disease but have not undergone deep brain stimulation. Subjects will be tested for GBA mutation status as part of this study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-mutation carriers without DBS</arm_group_label>
    <description>Parkinson's disease patients who have moderate to advanced disease but have not undergone deep brain stimulation. Subjects will be tested for GBA mutation status as part of this study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>GBA mutation carriers with DBS</arm_group_label>
    <description>Parkinson's disease patients who have moderate to advanced disease and have undergone deep brain stimulation. Subjects will be tested for GBA mutation status as part of this study.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>non-mutation carriers with DBS</arm_group_label>
    <description>Parkinson's disease patients who have moderate to advanced disease and have undergone deep brain stimulation. Subjects will be tested for GBA mutation status as part of this study.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>cognitive assessments</intervention_name>
    <description>Cognitive assessments will be performed at baseline, 1 year, and 2 years, depending on subject cohort placement</description>
    <arm_group_label>GBA mutation carriers with DBS</arm_group_label>
    <arm_group_label>GBA mutation carriers without DBS</arm_group_label>
    <arm_group_label>non-mutation carriers with DBS</arm_group_label>
    <arm_group_label>non-mutation carriers without DBS</arm_group_label>
  </intervention>
  <biospec_retention>Samples With DNA</biospec_retention>
  <biospec_descr>
    <textblock>
      blood will be retained for analysis of GBA metabolites.&#xD;
    </textblock>
  </biospec_descr>
  <eligibility>
    <study_pop>
      <textblock>
        Parkinson's disease subjects with onset of symptoms under age 60 with moderate to advanced&#xD;
        disease. Subjects can be with OR without deep brain stimulation.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Non-Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Parkinson's disease&#xD;
&#xD;
          -  onset of symptoms under age 60&#xD;
&#xD;
          -  at least 5 years of disease&#xD;
&#xD;
          -  with OR without deep brain stimulation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  dementia&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gian Pal</last_name>
    <role>Principal Investigator</role>
    <affiliation>Rutgers University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Gian D Pal, MD, MS</last_name>
    <phone>7322357733</phone>
    <email>gian.pal@rutgers.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Rutgers-Robert Wood Johnson Medical School</name>
      <address>
        <city>New Brunswick</city>
        <state>New Jersey</state>
        <zip>08901</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Gian Pal, MD</last_name>
      <phone>732-235-7733</phone>
      <email>gian.pal@rutgers.edu</email>
    </contact>
    <investigator>
      <last_name>Gian D Pal, MD, MS</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <results_reference>
    <citation>Pal GD, Hall D, Ouyang B, Phelps J, Alcalay R, Pauciulo MW, Nichols WC, Clark L, Mejia-Santana H, Blasucci L, Goetz CG, Comella C, Colcher A, Gan-Or Z, Rouleau GA, Marder K; Consortium on Risk for Early Onset Parkinson's Disease (CORE-PD) Investigators. Genetic and Clinical Predictors of Deep Brain Stimulation in Young-Onset Parkinson's Disease. Mov Disord Clin Pract. 2016 Sep-Oct;3(5):465-471. doi: 10.1002/mdc3.12309. Epub 2016 Jan 18.</citation>
    <PMID>27709117</PMID>
  </results_reference>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>July 25, 2017</study_first_submitted>
  <study_first_submitted_qc>July 28, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2017</study_first_posted>
  <last_update_submitted>June 1, 2023</last_update_submitted>
  <last_update_submitted_qc>June 1, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 2, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Rutgers, The State University of New Jersey</investigator_affiliation>
    <investigator_full_name>Gian Dev Pal, MD, MS</investigator_full_name>
    <investigator_title>Assistant Professor of Neurological Sciences</investigator_title>
  </responsible_party>
  <keyword>deep brain stimulation</keyword>
  <keyword>cognition</keyword>
  <keyword>young onset Parkinson disease</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Genetic Predisposition to Disease</mesh_term>
    <mesh_term>Cognitive Dysfunction</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/NCT03234478
org study id: Pro2020000729
secondary id: 1K23NS097625-01A1
nct id: NCT03234478
lead sponsor: 
collaborator: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Every year, approximately 9,000 Parkinson disease (PD) patients undergo deep brain stimulator
      (DBS) placement into the subthalamic nucleus (STN-DBS). Studies suggest that PD patients with
      mutations in the glucocerebrosidase (GBA) gene are at high risk for cognitive impairment and
      approximately 10-17% of subjects undergoing DBS carry GBA mutations. There may be an
      interaction between STN-DBS, which also impairs cognitive function, and GBA, resulting in
      worsened cognitive function. This project will 1) determine the relationship between GBA
      mutation status and post-operative STN-DBS cognitive function, 2) broaden genotype-phenotype
      relationships of GBA mutation carriers and 3) provide scientific knowledge regarding the
      longitudinal cognitive effects of DBS in GBA mutation carriers through repeated
      neuropsychological testing.
Parkinson disease (PD) is a neurodegenerative disease affecting at least 1 million people in
      the U.S. Each year, 9,000 PD patients undergo deep brain stimulator (DBS) placement into the
      subthalamic nucleus (STN-DBS), the most commonly used basal ganglia target. Despite motor
      improvement, up to 50% of patients have cognitive impairment after DBS. Cognitive impairment
      is associated with a 2-3 fold increase in mortality, progression to dementia, and nursing
      home placement. At present, subjects with cognitive impairment after DBS cannot be identified
      pre-operatively and the effects of DBS on cognitive function are not fully understood. A
      specific group of PD patients, carriers of mutations in the glucocerebrosidase (GBA) gene,
      are at particularly high risk for cognitive impairment. PD-GBA mutation carriers have
      dysfunction of the glucocerebrosidase (GCase) enzyme, resulting in more rapid accumulation
      and spread of Lewy bodies compared with non-mutation carriers. Clinically, PD-GBA mutation
      carriers have: (1) deficits in visual memory due to higher Lewy body burden in hippocampal
      and medial temporal regions, and (2) faster progression to dementia secondary to diffuse
      cortical Lewy body pathology. Approximately 10-17% of PD subjects with DBS carry GBA
      mutations, indicating that a substantial portion of the DBS population may be susceptible to
      cognitive problems. Importantly, STN-DBS itself can impair cognition through modulation of
      the striato-anterior cingulate cortex circuit, resulting in impulsivity and more errors when
      faced with tasks that rely on executive functions. Therefore, the central hypothesis is that
      PD-GBA mutation carriers have greater global cognitive decline after STN-DBS compared with
      PD-GBA mutation carriers without STN-DBS, and compared with non-mutation carriers with and
      without STN-DBS. This is a critical area of research because if an association between GBA
      and STN-DBS is detected, clinicians will be able to identify subjects at risk for worsened
      cognitive dysfunction through genetic testing and prevent harm by: (1) recommending that
      PD-GBA mutation carriers avoid STN-DBS, or (2) considering an alternative DBS target such as
      the globus pallidus interna (GPi) that may have less cognitive side effects. The following
      aims are proposed: Aim 1: Determine the longitudinal changes in global cognitive function in
      PD-GBA mutation carriers and non-mutation carriers with and without STN-DBS; Aim 2: Determine
      the specific pattern of cognitive dysfunction in PD-GBA mutation carriers and non-mutation
      carriers with and without STN-DBS; Aim 3: Determine the differential effects of DBS on
      cognitive function in the ON-stimulation state vs. OFF-stimulation state, comparing PD-GBA
      mutation and non-mutation carriers.
observational model: Cohort
time perspective: Prospective
measure: Mattis Dementia Rating Scale
time frame: 2 years
description: scale to assess global cognition
measure: NIH toolbox cognition battery
time frame: 1 year
description: iPAD based cognitive battery
measure: Neuro-QoL
time frame: 2 years
description: scale to assess quality of life
measure: PROMIS
time frame: 2 years
description: scale to assess quality of life
arm group label: GBA mutation carriers without DBS
description: Parkinson's disease patients who have moderate to advanced disease but have not undergone deep brain stimulation. Subjects will be tested for GBA mutation status as part of this study.
arm group label: non-mutation carriers without DBS
description: Parkinson's disease patients who have moderate to advanced disease but have not undergone deep brain stimulation. Subjects will be tested for GBA mutation status as part of this study.
arm group label: GBA mutation carriers with DBS
description: Parkinson's disease patients who have moderate to advanced disease and have undergone deep brain stimulation. Subjects will be tested for GBA mutation status as part of this study.
arm group label: non-mutation carriers with DBS
description: Parkinson's disease patients who have moderate to advanced disease and have undergone deep brain stimulation. Subjects will be tested for GBA mutation status as part of this study.
intervention type: Other
intervention name: cognitive assessments
description: Cognitive assessments will be performed at baseline, 1 year, and 2 years, depending on subject cohort placement
arm group label: GBA mutation carriers with DBS
arm group label: GBA mutation carriers without DBS
arm group label: non-mutation carriers with DBS
arm group label: non-mutation carriers without DBS
blood will be retained for analysis of GBA metabolites.
study pop: 
sampling method: Non-Probability Sample
criteria: 
gender: All
minimum age: 30 Years
maximum age: 75 Years
healthy volunteers: No
last name: Gian Pal
role: Principal Investigator
affiliation: Rutgers University
last name: Gian D Pal, MD, MS
phone: 7322357733
email: gian.pal@rutgers.edu
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
citation: Pal GD, Hall D, Ouyang B, Phelps J, Alcalay R, Pauciulo MW, Nichols WC, Clark L, Mejia-Santana H, Blasucci L, Goetz CG, Comella C, Colcher A, Gan-Or Z, Rouleau GA, Marder K; Consortium on Risk for Early Onset Parkinson's Disease (CORE-PD) Investigators. Genetic and Clinical Predictors of Deep Brain Stimulation in Young-Onset Parkinson's Disease. Mov Disord Clin Pract. 2016 Sep-Oct;3(5):465-471. doi: 10.1002/mdc3.12309. Epub 2016 Jan 18.
PMID: 27709117
responsible party type: Principal Investigator
investigator affiliation: Rutgers, The State University of New Jersey
investigator full name: Gian Dev Pal, MD, MS
investigator title: Assistant Professor of Neurological Sciences
mesh term: Parkinson Disease
mesh term: Genetic Predisposition to Disease
mesh term: Cognitive Dysfunction
sharing ipd: Undecided