Brain Perfusion & Oxygenation in Parkinson's Disease With NOH

Parkinson Disease Clinical Trial

Official title:

Evaluation of Brain Perfusion and Oxygenation in PD Patients With Neurogenic Orthostatic Hypotension: 4 Week Comparison of Droxidopa Versus Placebo

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03229174
• Other study ID #: Pro00013931
• Status: Completed
• Phase: Phase 4
• Start date: August 23, 2018
• Est. completion date: February 2, 2022

Study information

• Verified date: September 2022
• Source: The Methodist Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 17
• Est. completion date: February 2, 2022
• Est. primary completion date: February 2, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypotension
• Hypotension, Orthostatic
• Neurogenic Orthostatic Hypotension
• Parkinson Disease

Intervention

Drug:
• Droxidopa
Droxidopa initial dose 100mg TID, titrated in increments of 100mg every 24-48 hours to symptomatic response.
• Placebo
Placebo (sugar pill)

Locations

Country	Name	City	State
United States	Houston Methodist Hospital	Houston	Texas

Sponsors (2)

Lead Sponsor	Collaborator
William Ondo, MD	Lundbeck LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assessment of depressive symptoms	Beck Depression Inventory	8 weeks
Other	Assessment of sleepiness	Epworth sleepiness scale (ESS)	8 weeks
Other	Assessment of cognitive changes	Montreal cognitive assessment (MOCA)	8 weeks
Other	Assessment of fatigue	Fatigue severity scale (FSS)	8 weeks
Other	Participant impression of light-headedness	Subjective assessment of "light-headedness"	8 weeks
Primary	Cerebral perfusion	Cerebral perfusion measured by trans-cranial ultrasound of middle cerebral artery "supine and standing" delta.	8 weeks
Primary	Brain oxygenation	Brain oxygenation as measured by cerebral pulse oximetry device, delta between supine and standing	8 weeks
Secondary	Arteriole Blood Pressure	Change in arteriole BP (supine/standing) via tilt table	8 weeks
Secondary	R-R variability	changes in autonomic influence on heart rate placebo vs drug	8 weeks
Secondary	Orthostatic hypotension	Orthostatic hypotension scale	8 weeks
Secondary	Assessment of Parkinson's disease symptoms	Movement disorder society- Unified parkinson disease rating scale (MDS-UPDRS)	8 weeks
Secondary	Assessment of gait and falls	Timed Up and Go test	8 weeks