<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/NCT02967250</url>
  </required_header>
  <id_info>
    <org_study_id>NEUR-2016-18222</org_study_id>
    <nct_id>NCT02967250</nct_id>
  </id_info>
  <brief_title>Brain Bioenergetics in Parkinson's Disease and Response to Repeated Oral UDCA Treatment</brief_title>
  <official_title>7T Magnetic Resonance Spectroscopy Monitoring Brain Bioenergetics in Parkinson's Disease and Response to Repeated Oral UDCA Treatment</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Minnesota</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Minnesota</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The objective of this study is to understand the bioenergetic impairments that underlie&#xD;
      Parkinson's disease (PD) and evaluating treatments that may improve abnormal mitochondrial&#xD;
      function that is present in PD. The hypothesis is that repeated oral dosing of UDCA will&#xD;
      result in increased brain ATP levels in individuals with Parkinson's disease (PD). The&#xD;
      specific aims are 1.) to measure plasma UDCA levels in individuals with PD at baseline and&#xD;
      after four weeks of repeated high doses of oral UDCA (50mg/kg/day) and 2.) to measure&#xD;
      cortical bioenergetic profile and ATPase activity (as ascertained through MRS) in those with&#xD;
      PD at baseline and at four weeks after repeated high doses of oral UDCA (50mg/kg/day)&#xD;
      simultaneously. Secondary aims are to characterize oral UDCA pharmacokinetics and develop a&#xD;
      pharmacokinetic/pharmacodynamic model to characterize the relationship between peripheral&#xD;
      measurements of UDCA (and associated conjugates) and peripheral measures and/or central&#xD;
      (brain) bioenergetic measurements.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of this study is to understand the bioenergetic impairments that underlie&#xD;
      Parkinson's disease (PD) and evaluating treatments that may improve abnormal mitochondrial&#xD;
      function that is present in PD. High field - 7 tesla (T) - magnetic resonance spectroscopy&#xD;
      (MRS) is able to non-invasively assess for changes in brain energetics and will be used to&#xD;
      evaluate the effects that repeated oral doses of the mitochondrial enhancer ursodeoxycholic&#xD;
      acid (UDCA) has on brain bioenergetics derived from MRS measurements. This study will combine&#xD;
      results obtained using MRS brain scans along with peripheral measurements of bile acids&#xD;
      (e.g., total UDCA). This research will require at least 2 visits: baseline evaluation and at&#xD;
      approximately 6 weeks after subjects are on a stable oral dose for 4 weeks. Participants will&#xD;
      provide their medical history during the first visit, and undergo a physical examination and&#xD;
      rating scale each visit (duration: ~1 hour) as well as a brain MRI scan (1-1.5 hours). Blood&#xD;
      will be obtained at both visits to monitor for adverse effects as well as to assess for&#xD;
      changes in bile acids from orally administered UDCA. If additional funding is obtained we may&#xD;
      have another visit added between the first and second assessments to obtain additional blood&#xD;
      measurements and MRS data.&#xD;
&#xD;
      Since there is extensive animal and cell model data supporting the rationale for a&#xD;
      therapeutic trial of UDCA in PD, and because MRS methods can non-invasively detect changes in&#xD;
      brain chemistry we propose a study to evaluate the effects of a 4-6 weeks of high-dose oral&#xD;
      UDCA on central (brain) and peripheral measures (through MRS and blood measurements,&#xD;
      respectively) in individuals with PD and healthy controls. The hypothesis and specific aims&#xD;
      are as follows:&#xD;
&#xD;
      Hypothesis: Repeated oral dosing of UDCA will result in increased brain ATP levels in&#xD;
      individuals with Parkinson's disease (PD).&#xD;
&#xD;
      Specific Aims:&#xD;
&#xD;
        1. Measure plasma UDCA levels in individuals with PD at baseline and after four weeks of&#xD;
           repeated high doses of oral UDCA (50mg/kg/day).&#xD;
&#xD;
        2. Measure cortical bioenergetic profile and ATPase activity (as ascertained through MRS)&#xD;
           in those with PD at baseline and at four weeks after repeated high doses of oral UDCA&#xD;
           (50mg/kg/day) simultaneously with Aim 1.&#xD;
&#xD;
      Secondary Aims:&#xD;
&#xD;
        1. Characterize oral UDCA pharmacokinetics&#xD;
&#xD;
        2. Develop a pharmacokinetic/pharmacodynamic model to characterize the relationship between&#xD;
           peripheral measurements of UDCA (and associated conjugates) and peripheral measures&#xD;
           and/or central (brain) bioenergetic measurements.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 1, 2020</start_date>
  <completion_date type="Actual">February 28, 2022</completion_date>
  <primary_completion_date type="Actual">February 28, 2022</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in ATP concentration</measure>
    <time_frame>prior to intervention and at 6 weeks of intervention</time_frame>
    <description>measurement of ATP concentrations in brain using 7T MRS</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>UDCA pharmacokinetics</measure>
    <time_frame>at 6 weeks of intervention</time_frame>
    <description>measurement of UDCA concentration in plasma will be used to determine pharmacokinetics</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Ursodeoxycholic acid treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Each subject will receive UDCA intervention for six weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>ursodeoxycholic acid</intervention_name>
    <description>Subjects will be provided ~50mg/kg/day (based on the use of 250 and 500mg capsules) of UDCA to be divided into 3 equal daily doses and titrated up over ~2 weeks to a stable dose for 4 weeks.</description>
    <arm_group_label>Ursodeoxycholic acid treatment</arm_group_label>
    <other_name>Ursodiol</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. All participants must be 18 years or older.&#xD;
&#xD;
          2. All enrollees must understand and cooperate with requirements of the study and be able&#xD;
             to provide written informed consent&#xD;
&#xD;
          3. Individuals with medically stable mild to moderate Parkinson's disease or healthy&#xD;
             controls (as determined by enrolling investigator)&#xD;
&#xD;
          4. All participants must not have taken UDCA for 4 weeks prior to the study.&#xD;
&#xD;
          5. Absence of dementia in all subjects, as determined by pre-scanning cognitive&#xD;
             assessment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Inability to undergo MRI scanning without sedation and other MRI counterindications,&#xD;
             such as metal in the body.&#xD;
&#xD;
          2. Medically unstable conditions&#xD;
&#xD;
          3. Pregnant or lactating or those women of child-bearing age that are not using&#xD;
             acceptable forms of contraception&#xD;
&#xD;
          4. Unable to adhere to study protocol as determined by the PI&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Lisa Coles, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Paul Tuite, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Minnesota</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Center for Magnetic Resonance Research</name>
      <address>
        <city>Minneapolis</city>
        <state>Minnesota</state>
        <zip>55455</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2022</verification_date>
  <study_first_submitted>September 13, 2016</study_first_submitted>
  <study_first_submitted_qc>November 15, 2016</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 18, 2016</study_first_posted>
  <last_update_submitted>March 7, 2022</last_update_submitted>
  <last_update_submitted_qc>March 7, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 22, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Ursodeoxycholic Acid</mesh_term>
  </intervention_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/NCT02967250
org study id: NEUR-2016-18222
nct id: NCT02967250
lead sponsor: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The objective of this study is to understand the bioenergetic impairments that underlie
      Parkinson's disease (PD) and evaluating treatments that may improve abnormal mitochondrial
      function that is present in PD. The hypothesis is that repeated oral dosing of UDCA will
      result in increased brain ATP levels in individuals with Parkinson's disease (PD). The
      specific aims are 1.) to measure plasma UDCA levels in individuals with PD at baseline and
      after four weeks of repeated high doses of oral UDCA (50mg/kg/day) and 2.) to measure
      cortical bioenergetic profile and ATPase activity (as ascertained through MRS) in those with
      PD at baseline and at four weeks after repeated high doses of oral UDCA (50mg/kg/day)
      simultaneously. Secondary aims are to characterize oral UDCA pharmacokinetics and develop a
      pharmacokinetic/pharmacodynamic model to characterize the relationship between peripheral
      measurements of UDCA (and associated conjugates) and peripheral measures and/or central
      (brain) bioenergetic measurements.
The objective of this study is to understand the bioenergetic impairments that underlie
      Parkinson's disease (PD) and evaluating treatments that may improve abnormal mitochondrial
      function that is present in PD. High field - 7 tesla (T) - magnetic resonance spectroscopy
      (MRS) is able to non-invasively assess for changes in brain energetics and will be used to
      evaluate the effects that repeated oral doses of the mitochondrial enhancer ursodeoxycholic
      acid (UDCA) has on brain bioenergetics derived from MRS measurements. This study will combine
      results obtained using MRS brain scans along with peripheral measurements of bile acids
      (e.g., total UDCA). This research will require at least 2 visits: baseline evaluation and at
      approximately 6 weeks after subjects are on a stable oral dose for 4 weeks. Participants will
      provide their medical history during the first visit, and undergo a physical examination and
      rating scale each visit (duration: ~1 hour) as well as a brain MRI scan (1-1.5 hours). Blood
      will be obtained at both visits to monitor for adverse effects as well as to assess for
      changes in bile acids from orally administered UDCA. If additional funding is obtained we may
      have another visit added between the first and second assessments to obtain additional blood
      measurements and MRS data.

      Since there is extensive animal and cell model data supporting the rationale for a
      therapeutic trial of UDCA in PD, and because MRS methods can non-invasively detect changes in
      brain chemistry we propose a study to evaluate the effects of a 4-6 weeks of high-dose oral
      UDCA on central (brain) and peripheral measures (through MRS and blood measurements,
      respectively) in individuals with PD and healthy controls. The hypothesis and specific aims
      are as follows:

      Hypothesis: Repeated oral dosing of UDCA will result in increased brain ATP levels in
      individuals with Parkinson's disease (PD).

      Specific Aims:

        1. Measure plasma UDCA levels in individuals with PD at baseline and after four weeks of
           repeated high doses of oral UDCA (50mg/kg/day).

        2. Measure cortical bioenergetic profile and ATPase activity (as ascertained through MRS)
           in those with PD at baseline and at four weeks after repeated high doses of oral UDCA
           (50mg/kg/day) simultaneously with Aim 1.

      Secondary Aims:

        1. Characterize oral UDCA pharmacokinetics

        2. Develop a pharmacokinetic/pharmacodynamic model to characterize the relationship between
           peripheral measurements of UDCA (and associated conjugates) and peripheral measures
           and/or central (brain) bioenergetic measurements.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change in ATP concentration
time frame: prior to intervention and at 6 weeks of intervention
description: measurement of ATP concentrations in brain using 7T MRS
measure: UDCA pharmacokinetics
time frame: at 6 weeks of intervention
description: measurement of UDCA concentration in plasma will be used to determine pharmacokinetics
arm group label: Ursodeoxycholic acid treatment
arm group type: Experimental
description: Each subject will receive UDCA intervention for six weeks.
intervention type: Drug
intervention name: ursodeoxycholic acid
description: Subjects will be provided ~50mg/kg/day (based on the use of 250 and 500mg capsules) of UDCA to be divided into 3 equal daily doses and titrated up over ~2 weeks to a stable dose for 4 weeks.
arm group label: Ursodeoxycholic acid treatment
other name: Ursodiol
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Lisa Coles, PhD
role: Principal Investigator
affiliation: University of Minnesota
last name: Paul Tuite, MD
role: Principal Investigator
affiliation: University of Minnesota
facility: 
country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Ursodeoxycholic Acid
sharing ipd: Undecided