<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/NCT03782753</url>
  </required_header>
  <id_info>
    <org_study_id>249061</org_study_id>
    <nct_id>NCT03782753</nct_id>
  </id_info>
  <brief_title>Molecular Pathology and Neuronal Networks in LRRK2 Parkinson's Disease</brief_title>
  <official_title>Longitudinal Study of Molecular Pathology and Neuronal Networks in Leucine-rich Repeat Kinase 2 Carriers and Idiopathic Parkinson's Disease Patients and Healthy Controls Using PET, MR Imaging, and Other Markers of in Vivo Pathology</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>King's College London</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>GlaxoSmithKline</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>King's College London</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>
      Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized clinically&#xD;
      by bradykinesia, resting tremor, rigidity, and postural instability. Little is known about&#xD;
      the mechanisms underlying neuronal degeneration in PD and currently, no treatment is&#xD;
      available to halt disease progression in PD.&#xD;
&#xD;
      The pathophysiological characterisation of phenomena occurring in the time window between the&#xD;
      pathological start of the disease and the onset of motor symptoms is crucial to develop&#xD;
      potential neuroprotective agents.&#xD;
&#xD;
      Several genes have been discovered providing important insights on the pathogenesis of PD.&#xD;
      Mutations of Leucine-rich repeat kinase 2 (LRRK2) are associated with 2-5% of all PD cases in&#xD;
      North American Caucasians. LRRK2 is an enzyme that in humans is encoded by the autosomal&#xD;
      dominant Parkinson's disease-8 (PARK8) gene, which is associated with an increased risk of&#xD;
      PD.&#xD;
&#xD;
      Clinical and digital biomarkers, blood and cerebrospinal fluid (CSF) biomarkers and molecular&#xD;
      positron emission tomography (PET) imaging, with specific radioligands, provide invaluable&#xD;
      insights to help understand and characterise disease pathophysiology.&#xD;
&#xD;
      The investigators aim to characterize molecular phenomena underlying LRRK2 PD with the hope&#xD;
      of providing further insights into possible mechanisms taking place in PD and to help&#xD;
      identify targets for disease-modifying therapeutics.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 15, 2019</start_date>
  <completion_date type="Actual">June 23, 2023</completion_date>
  <primary_completion_date type="Actual">January 14, 2021</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>Other</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in serotonergic transmission in the ventral and dorsal raphe nuclei, and in raphe projection areas, in LRRK2-PD compared to idiopathic PD.</measure>
    <time_frame>One year</time_frame>
    <description>The study's main outcome measure is changes in serotonergic neurotransmission within specific brain regions. This will be assessed with positron emission tomography (PET) imaging using the readioligand 11C-labeled 3-amino-4 -(2-dimethylaminomethyl-phenylsulfanyl)benzonitrile ([11C]DASB).</description>
  </primary_outcome>
  <number_of_groups>3</number_of_groups>
  <enrollment type="Actual">59</enrollment>
  <condition>Parkinson Disease, PARK8</condition>
  <condition>Parkinson Disease</condition>
  <condition>Idiopathic Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <description>25 LRRK2-PD patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <description>25 idiopathic PD patients</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group C</arm_group_label>
    <description>25 HC subjects</description>
  </arm_group>
  <eligibility>
    <study_pop>
      <textblock>
        LRRK2 PD patients, idiopathic PD patients and healthy controls.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        All groups&#xD;
&#xD;
          -  Women of child-bearing potential must use protocol-defined contraceptive measures and&#xD;
             must have a negative β-hCG test at screening. For sexually active subjects (except&#xD;
             females of non-childbearing potential), condoms should be used in addition to other&#xD;
             birth control methods during the study, for 15 days after the last dose of&#xD;
             investigational drug, and for 3 months after the last administration of PET or SPECT&#xD;
             ligands. All male subjects must agree to refrain from donating sperm during the study,&#xD;
             for 15 days following the last dose of investigational drug, and for 3 months after&#xD;
             the last administration of PET or SPECT ligands. It is important that male subjects&#xD;
             not impregnate others while in the study.&#xD;
&#xD;
          -  Adequate visual and auditory acuity to complete the psychological testing.&#xD;
&#xD;
        Idiopathic PD group&#xD;
&#xD;
          -  Clinical diagnosis of Parkinson's disease meeting the Movement Disorder Society&#xD;
             Clinical Diagnostic Criteria (i.e. not induced by drugs or other diseases or carriers&#xD;
             of PD risk genes such as LRRK2, SNCA, PARK2 etc.).&#xD;
&#xD;
          -  Hoehn and Yahr scale stage 1 or 2.&#xD;
&#xD;
          -  Patients who are drug-naïve (never been treated with dopamine agonists or levodopa) or&#xD;
             on dopamine replacement therapy.&#xD;
&#xD;
          -  Patients who have received the diagnosis of idiopathic PD within three years for&#xD;
             drug-naïve patients or within eight years for patients on dopamine replacement&#xD;
             therapy.&#xD;
&#xD;
        LRRK2 PD group&#xD;
&#xD;
          -  Clinical diagnosis of Parkinson's disease meeting the Movement Disorder Society&#xD;
             Clinical Diagnostic Criteria and genetic confirmation of being carriers of LRRK2 PD&#xD;
             risk genes, diagnosed after the age of 30 years.&#xD;
&#xD;
          -  Hoehn and Yahr scale stage 1 or 2.&#xD;
&#xD;
          -  Patients who are drug-naïve (never been treated with dopamine agonists or levodopa) or&#xD;
             on dopamine replacement therapy.&#xD;
&#xD;
          -  Patients who have received the diagnosis of idiopathic PD within three years for&#xD;
             drug-naïve patients or within eight years for patients on dopamine replacement&#xD;
             therapy.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who had previous surgery for PD (including but not limited to deep brain&#xD;
             stimulation [DBS] or cell transplantation).&#xD;
&#xD;
          -  Patients who are treated with duodopa or apomorphine.&#xD;
&#xD;
          -  Patients taking serotonin acting drugs such as antidepressants (i.e. tricyclic or&#xD;
             selective serotonin reuptake inhibitors etc.)&#xD;
&#xD;
          -  Patients taking drugs acting on SV2A such as antiepileptics (i.e. levetiracetam or&#xD;
             brivaracetam etc.)&#xD;
&#xD;
          -  Pregnancy or breastfeeding.&#xD;
&#xD;
          -  Patients with current or a recent history of drug or alcohol abuse/dependence.&#xD;
&#xD;
          -  Patients who have other neurological disorders and known intracranial co-morbidities&#xD;
             such as stroke, haemorrhage, space-occupying lesions.&#xD;
&#xD;
          -  Presence of any clinically significant medical condition (including cardiovascular,&#xD;
             respiratory, cerebrovascular, hematological, hepatic, renal, gastrointestinal, or&#xD;
             other disease) that, based on the judgment of the investigator, is clinically&#xD;
             unstable, is likely to deteriorate during the course of the study, could put the&#xD;
             patient at risk because of participation in the study, could affect the subject's&#xD;
             ability to complete the study, or could influence the study results.&#xD;
&#xD;
          -  History of suicidal behavior or active suicidal ideation.&#xD;
&#xD;
          -  Within 1 year prior to screen or between screen and baseline (Day -1), any of the&#xD;
             following: myocardial infarction; hospitalization for congestive heart failure;&#xD;
             hospitalization for, or symptoms of, unstable angina; or syncope not related to PD.&#xD;
&#xD;
          -  History or presence of renal disease or impaired renal function.&#xD;
&#xD;
          -  Clinically important infection (e.g., chronic, persistent, or acute infection) within&#xD;
             30 days prior to screen or between screen and baseline (Day -1).&#xD;
&#xD;
          -  History of cancer within the last 5 years, with the exception of nonmetastatic basal&#xD;
             cell carcinoma of the skin.&#xD;
&#xD;
          -  Clinically significant blood clotting or bleeding disorder, including clinically&#xD;
             significant abnormal findings in laboratory assessments of coagulation or hematology.&#xD;
&#xD;
          -  Use of antipsychotic medication within 3 months prior to screen or between screen and&#xD;
             baseline (Day -1).&#xD;
&#xD;
          -  Use of any anticoagulant within 30 days prior to baseline PET scan.&#xD;
&#xD;
          -  Use of any oral corticosteroid within 30 days prior to baseline PET scan.&#xD;
&#xD;
          -  Use of metoclopramide within 30 days prior to baseline (Day -1).&#xD;
&#xD;
          -  Use of any thyroid medication within 30 days prior to baseline (Day -1).&#xD;
&#xD;
          -  Regular use (e.g., taken &gt; 3 days/week) of narcotic pain medications within 30 days&#xD;
             prior to baseline (Day -1).&#xD;
&#xD;
          -  Presence of any of the following MRI contraindications: pacemaker; cardiac&#xD;
             defibrillator; spinal cord or vagus nerve stimulator; aneurysm clip; artificial heart&#xD;
             valve; recent coronary or carotid stent; ear implant; CSF shunt; other implanted&#xD;
             medical device (e.g., Swan-Ganz catheter, insulin pump); or metal fragments or foreign&#xD;
             objects in the eyes, skin, or body.&#xD;
&#xD;
          -  Negative Allen test in both hands, unless the brachial artery is used for arterial&#xD;
             cannulation.&#xD;
&#xD;
          -  Claustrophobia and history of back pain that makes prolonged laying on the PET or MRI&#xD;
             scanner intolerable.&#xD;
&#xD;
          -  Initiation or change in pharmacologic therapy for symptoms of PD within 30 days prior&#xD;
             to screen or between screen and baseline (Day -1).&#xD;
&#xD;
        In addition, the following are exclusionary for subjects participating in CSF sampling:&#xD;
&#xD;
        - Any spinal malformations or other aspects (e.g., tattoos) or other clinical findings&#xD;
        (e.g., papilledema seen with ophthalmoscopy) that may complicate or contraindicate lumbar&#xD;
        puncture, as judged by the investigator.&#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>
  <location>
    <facility>
      <name>King's College London</name>
      <address>
        <city>London</city>
        <country>United Kingdom</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United Kingdom</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>December 14, 2018</study_first_submitted>
  <study_first_submitted_qc>December 18, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 20, 2018</study_first_posted>
  <last_update_submitted>June 26, 2023</last_update_submitted>
  <last_update_submitted_qc>June 26, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">June 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Parkinson Disease</keyword>
  <keyword>LRRK2</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/NCT03782753
org study id: 249061
nct id: NCT03782753
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Parkinson's Disease (PD) is a progressive neurodegenerative disease characterized clinically
      by bradykinesia, resting tremor, rigidity, and postural instability. Little is known about
      the mechanisms underlying neuronal degeneration in PD and currently, no treatment is
      available to halt disease progression in PD.

      The pathophysiological characterisation of phenomena occurring in the time window between the
      pathological start of the disease and the onset of motor symptoms is crucial to develop
      potential neuroprotective agents.

      Several genes have been discovered providing important insights on the pathogenesis of PD.
      Mutations of Leucine-rich repeat kinase 2 (LRRK2) are associated with 2-5% of all PD cases in
      North American Caucasians. LRRK2 is an enzyme that in humans is encoded by the autosomal
      dominant Parkinson's disease-8 (PARK8) gene, which is associated with an increased risk of
      PD.

      Clinical and digital biomarkers, blood and cerebrospinal fluid (CSF) biomarkers and molecular
      positron emission tomography (PET) imaging, with specific radioligands, provide invaluable
      insights to help understand and characterise disease pathophysiology.

      The investigators aim to characterize molecular phenomena underlying LRRK2 PD with the hope
      of providing further insights into possible mechanisms taking place in PD and to help
      identify targets for disease-modifying therapeutics.
observational model: Case-Control
time perspective: Other
measure: Changes in serotonergic transmission in the ventral and dorsal raphe nuclei, and in raphe projection areas, in LRRK2-PD compared to idiopathic PD.
time frame: One year
description: The study's main outcome measure is changes in serotonergic neurotransmission within specific brain regions. This will be assessed with positron emission tomography (PET) imaging using the readioligand 11C-labeled 3-amino-4 -(2-dimethylaminomethyl-phenylsulfanyl)benzonitrile ([11C]DASB).
arm group label: Group A
description: 25 LRRK2-PD patients
arm group label: Group B
description: 25 idiopathic PD patients
arm group label: Group C
description: 25 HC subjects
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 30 Years
maximum age: 80 Years
healthy volunteers: Accepts Healthy Volunteers
facility: 
country: United Kingdom
responsible party type: Sponsor
mesh term: Parkinson Disease