<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/NCT03229174</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00013931</org_study_id>
    <nct_id>NCT03229174</nct_id>
  </id_info>
  <brief_title>Brain Perfusion &amp; Oxygenation in Parkinson's Disease With NOH</brief_title>
  <official_title>Evaluation of Brain Perfusion and Oxygenation in PD Patients With Neurogenic Orthostatic Hypotension: 4 Week Comparison of Droxidopa Versus Placebo</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>William Ondo, MD</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Lundbeck LLC</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>The Methodist Hospital Research Institute</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>
    <is_us_export>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a double blind placebo controlled trial in Parkinson's disease (PD) patients with&#xD;
      neurogenic orthostatic hypotension (NOH). Investigators hypothesize that the study drug&#xD;
      (droxidopa) may improve cerebral perfusion more robustly than systemic BP, possibly by direct&#xD;
      action within the CNS vasculature. This study is designed to determine if droxidopa improves&#xD;
      cerebral perfusion measures in PD patients with NOH, in addition to peripheral BP measures&#xD;
      and subjective responses.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. This is a double blind placebo controlled trial in PD patients with NOH. The controlled&#xD;
           portion consists of two visits (baseline and week 4) and a phone call (week 2). An open&#xD;
           label extension will include a phone call (week 6) and a final visit (week 8). Subjects&#xD;
           will undergo a baseline assessment including continuous tilt table (10 minutes supine /&#xD;
           30 minutes at 70o / 10 minute supine) measurements of arteriole BP. Assessment will be&#xD;
           done in the &quot;on&quot; state 1-3 hours after last dose and 1-3 hours after last meal. During&#xD;
           both supine and standing positions, subjects will undergo a quantified transcranial&#xD;
           cerebral ultrasound of the middle cerebral artery. A secondary analysis of the posterior&#xD;
           circulation (basilar artery) will also be done when technically possible. An experienced&#xD;
           technician will use a Spencer ST-3 Transcranial Doppler and MHz frequency probes&#xD;
           (Spencer Technologies, Redmond WA), with ability to display all data in real time with&#xD;
           M-mode and spectral waveform, depth of sample volume, size of sample volume, peak&#xD;
           systolic and end diastolic velocities, pulsatility index and frequency of transducer.&#xD;
           Cerebral oxygenation will be assessed throughout the tilt table with an FORE-SIGHT ELITE&#xD;
           Oximetry System (CASMED) with FORE-SIGHT ELITE large advanced sensor. Mean/Max/Min vales&#xD;
           will be analyzed. The tilt table BP and HR monitor with autonomic function will be&#xD;
           recorded with a Task Force monitor from CNsystem. Subjective assessments will be done&#xD;
           prior to the tilt table and will include demographics, general medical history, UPDRS,&#xD;
           and the orthostatic hypotension questionnaire, and some gait analysis. We will also&#xD;
           query their subjective &quot;light headedness&quot; throughout the tilt table test to determine&#xD;
           for objective correlates.&#xD;
&#xD;
        2. Subjects will be titrated with droxidopa or matching placebo over two weeks using&#xD;
           current guidelines. The dose will be held constant for the final two weeks and taken on&#xD;
           the day of the week 4 visit. After a safety and dose determination call at two weeks,&#xD;
           subjects will return at 4 weeks for an identical evaluation, along with clinical global&#xD;
           impressions of change.&#xD;
&#xD;
        3. All subjects will be allowed into a 4 week open label extension. They will start&#xD;
           titration at 100 mg droxidopa TID but can titrate up daily if preferred. After a safety&#xD;
           call (week 6) they will return for a final tilt table/ultrasound perfusion&#xD;
           study/oximetry study and subjective questionnaires. The patients will be provided two&#xD;
           additional weeks medication to ensure a safe transition to purchased droxidopa if&#xD;
           desired.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 23, 2018</start_date>
  <completion_date type="Actual">February 2, 2022</completion_date>
  <primary_completion_date type="Actual">February 2, 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Cerebral perfusion</measure>
    <time_frame>8 weeks</time_frame>
    <description>Cerebral perfusion measured by trans-cranial ultrasound of middle cerebral artery &quot;supine and standing&quot; delta.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Brain oxygenation</measure>
    <time_frame>8 weeks</time_frame>
    <description>Brain oxygenation as measured by cerebral pulse oximetry device, delta between supine and standing</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Arteriole Blood Pressure</measure>
    <time_frame>8 weeks</time_frame>
    <description>Change in arteriole BP (supine/standing) via tilt table</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>R-R variability</measure>
    <time_frame>8 weeks</time_frame>
    <description>changes in autonomic influence on heart rate placebo vs drug</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Orthostatic hypotension</measure>
    <time_frame>8 weeks</time_frame>
    <description>Orthostatic hypotension scale</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of Parkinson's disease symptoms</measure>
    <time_frame>8 weeks</time_frame>
    <description>Movement disorder society- Unified parkinson disease rating scale (MDS-UPDRS)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Assessment of gait and falls</measure>
    <time_frame>8 weeks</time_frame>
    <description>Timed Up and Go test</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Assessment of depressive symptoms</measure>
    <time_frame>8 weeks</time_frame>
    <description>Beck Depression Inventory</description>
  </other_outcome>
  <other_outcome>
    <measure>Assessment of sleepiness</measure>
    <time_frame>8 weeks</time_frame>
    <description>Epworth sleepiness scale (ESS)</description>
  </other_outcome>
  <other_outcome>
    <measure>Assessment of cognitive changes</measure>
    <time_frame>8 weeks</time_frame>
    <description>Montreal cognitive assessment (MOCA)</description>
  </other_outcome>
  <other_outcome>
    <measure>Assessment of fatigue</measure>
    <time_frame>8 weeks</time_frame>
    <description>Fatigue severity scale (FSS)</description>
  </other_outcome>
  <other_outcome>
    <measure>Participant impression of light-headedness</measure>
    <time_frame>8 weeks</time_frame>
    <description>Subjective assessment of &quot;light-headedness&quot;</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">17</enrollment>
  <condition>Parkinson Disease</condition>
  <condition>Neurogenic Orthostatic Hypotension</condition>
  <arm_group>
    <arm_group_label>Intervention phase</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Droxidopa unforced titration dose (starting at 100mg by mouth TID) or matching placebo and titrated over 2 weeks up to maximum of 600 TID. Efficacy evaluation of given dose at week 4</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Open label extension phase</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>All subjects allowed into a 4 week open label extension. Similar titration will start at 100mg Droxidopa three times a day (TID), but can be titrated up daily using the same dose escalation scale.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Droxidopa</intervention_name>
    <description>Droxidopa initial dose 100mg TID, titrated in increments of 100mg every 24-48 hours to symptomatic response.</description>
    <arm_group_label>Intervention phase</arm_group_label>
    <arm_group_label>Open label extension phase</arm_group_label>
    <other_name>Northera</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo</intervention_name>
    <description>Placebo (sugar pill)</description>
    <arm_group_label>Intervention phase</arm_group_label>
    <other_name>Sugar pill</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Idiopathic Parkinson's disease patients with orthostatic hypotension (Systolic Blood&#xD;
             Pressure drop of &gt; 20 mm hg or Diastolic Blood Pressure drop of &gt;10 mm hg measured at&#xD;
             some point) within a month of inclusion.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Age &gt;85&#xD;
&#xD;
          -  Concurrent use of Midodrine&#xD;
&#xD;
          -  Medical conditions that in the opinion of the investigator, might not allow for same&#xD;
             completion of the study i.e. unstable angina, neoplasm, etc&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>William Ondo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>The Methodist Hospital Research Institute</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Houston Methodist Hospital</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>April 21, 2017</study_first_submitted>
  <study_first_submitted_qc>July 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 25, 2017</study_first_posted>
  <last_update_submitted>September 1, 2022</last_update_submitted>
  <last_update_submitted_qc>September 1, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 6, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>The Methodist Hospital Research Institute</investigator_affiliation>
    <investigator_full_name>William Ondo, MD</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
    <mesh_term>Hypotension, Orthostatic</mesh_term>
    <mesh_term>Hypotension</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Droxidopa</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03229174
org study id: Pro00013931
nct id: NCT03229174
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
is us export: Yes
This is a double blind placebo controlled trial in Parkinson's disease (PD) patients with
      neurogenic orthostatic hypotension (NOH). Investigators hypothesize that the study drug
      (droxidopa) may improve cerebral perfusion more robustly than systemic BP, possibly by direct
      action within the CNS vasculature. This study is designed to determine if droxidopa improves
      cerebral perfusion measures in PD patients with NOH, in addition to peripheral BP measures
      and subjective responses.
1. This is a double blind placebo controlled trial in PD patients with NOH. The controlled
           portion consists of two visits (baseline and week 4) and a phone call (week 2). An open
           label extension will include a phone call (week 6) and a final visit (week 8). Subjects
           will undergo a baseline assessment including continuous tilt table (10 minutes supine /
           30 minutes at 70o / 10 minute supine) measurements of arteriole BP. Assessment will be
           done in the "on" state 1-3 hours after last dose and 1-3 hours after last meal. During
           both supine and standing positions, subjects will undergo a quantified transcranial
           cerebral ultrasound of the middle cerebral artery. A secondary analysis of the posterior
           circulation (basilar artery) will also be done when technically possible. An experienced
           technician will use a Spencer ST-3 Transcranial Doppler and MHz frequency probes
           (Spencer Technologies, Redmond WA), with ability to display all data in real time with
           M-mode and spectral waveform, depth of sample volume, size of sample volume, peak
           systolic and end diastolic velocities, pulsatility index and frequency of transducer.
           Cerebral oxygenation will be assessed throughout the tilt table with an FORE-SIGHT ELITE
           Oximetry System (CASMED) with FORE-SIGHT ELITE large advanced sensor. Mean/Max/Min vales
           will be analyzed. The tilt table BP and HR monitor with autonomic function will be
           recorded with a Task Force monitor from CNsystem. Subjective assessments will be done
           prior to the tilt table and will include demographics, general medical history, UPDRS,
           and the orthostatic hypotension questionnaire, and some gait analysis. We will also
           query their subjective "light headedness" throughout the tilt table test to determine
           for objective correlates.

        2. Subjects will be titrated with droxidopa or matching placebo over two weeks using
           current guidelines. The dose will be held constant for the final two weeks and taken on
           the day of the week 4 visit. After a safety and dose determination call at two weeks,
           subjects will return at 4 weeks for an identical evaluation, along with clinical global
           impressions of change.

        3. All subjects will be allowed into a 4 week open label extension. They will start
           titration at 100 mg droxidopa TID but can titrate up daily if preferred. After a safety
           call (week 6) they will return for a final tilt table/ultrasound perfusion
           study/oximetry study and subjective questionnaires. The patients will be provided two
           additional weeks medication to ensure a safe transition to purchased droxidopa if
           desired.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Cerebral perfusion
time frame: 8 weeks
description: Cerebral perfusion measured by trans-cranial ultrasound of middle cerebral artery "supine and standing" delta.
measure: Brain oxygenation
time frame: 8 weeks
description: Brain oxygenation as measured by cerebral pulse oximetry device, delta between supine and standing
measure: Arteriole Blood Pressure
time frame: 8 weeks
description: Change in arteriole BP (supine/standing) via tilt table
measure: R-R variability
time frame: 8 weeks
description: changes in autonomic influence on heart rate placebo vs drug
measure: Orthostatic hypotension
time frame: 8 weeks
description: Orthostatic hypotension scale
measure: Assessment of Parkinson's disease symptoms
time frame: 8 weeks
description: Movement disorder society- Unified parkinson disease rating scale (MDS-UPDRS)
measure: Assessment of gait and falls
time frame: 8 weeks
description: Timed Up and Go test
measure: Assessment of depressive symptoms
time frame: 8 weeks
description: Beck Depression Inventory
measure: Assessment of sleepiness
time frame: 8 weeks
description: Epworth sleepiness scale (ESS)
measure: Assessment of cognitive changes
time frame: 8 weeks
description: Montreal cognitive assessment (MOCA)
measure: Assessment of fatigue
time frame: 8 weeks
description: Fatigue severity scale (FSS)
measure: Participant impression of light-headedness
time frame: 8 weeks
description: Subjective assessment of "light-headedness"
arm group label: Intervention phase
arm group type: Experimental
description: Droxidopa unforced titration dose (starting at 100mg by mouth TID) or matching placebo and titrated over 2 weeks up to maximum of 600 TID. Efficacy evaluation of given dose at week 4
arm group label: Open label extension phase
arm group type: Other
description: All subjects allowed into a 4 week open label extension. Similar titration will start at 100mg Droxidopa three times a day (TID), but can be titrated up daily using the same dose escalation scale.
intervention type: Drug
intervention name: Droxidopa
description: Droxidopa initial dose 100mg TID, titrated in increments of 100mg every 24-48 hours to symptomatic response.
arm group label: Intervention phase
arm group label: Open label extension phase
other name: Northera
intervention type: Drug
intervention name: Placebo
description: Placebo (sugar pill)
arm group label: Intervention phase
other name: Sugar pill
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: William Ondo, MD
role: Principal Investigator
affiliation: The Methodist Hospital Research Institute
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: The Methodist Hospital Research Institute
investigator full name: William Ondo, MD
investigator title: Principal Investigator
mesh term: Parkinson Disease
mesh term: Hypotension, Orthostatic
mesh term: Hypotension
mesh term: Droxidopa
sharing ipd: No