Brain Perfusion & Oxygenation in Parkinson's Disease With NOH

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