Brain Perfusion & Oxygenation in Parkinson's Disease With NOH
Brain Perfusion & Oxygenation in Parkinson's Disease With NOH
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.
Inclusion Criteria:

 -  Idiopathic Parkinson's disease patients with orthostatic hypotension (Systolic Blood
 Pressure drop of > 20 mm hg or Diastolic Blood Pressure drop of >10 mm hg measured at
 some point) within a month of inclusion.

 Exclusion Criteria:

 -  Age >85

 -  Concurrent use of Midodrine

 -  Medical conditions that in the opinion of the investigator, might not allow for same
 completion of the study i.e. unstable angina, neoplasm, etc