Brain Perfusion & Oxygenation in Parkinson's Disease With NOH
Condition: Parkinson Disease; Neurogenic Orthostatic Hypotension
MeSH terms: Parkinson Disease; Hypotension, Orthostatic; Hypotension
Study type: Interventional
Phase: Phase 4

Summary: 
      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.
    

Detailed description: 
      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.
    

Intervention name(s): Droxidopa; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Droxidopa initial dose 100mg TID, titrated in increments of 100mg every 24-48 hours to symptomatic response.; Placebo (sugar pill)
Other intervention name(s): Northera; Sugar pill
Intervention MeSH terms: Droxidopa
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment