Brain Perfusion & Oxygenation in Parkinson's Disease With NOH

NCT ID: NCT03229174

Last Updated: 2022-09-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 17 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-08-23
• Study Completion Date: 2022-02-02

Brief 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.

Conditions

Parkinson Disease; Neurogenic Orthostatic Hypotension

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Intervention phase

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

Group Type: EXPERIMENTAL

Droxidopa

Intervention Type: DRUG

Droxidopa initial dose 100mg TID, titrated in increments of 100mg every 24-48 hours to symptomatic response.

Placebo

Intervention Type: DRUG

Placebo (sugar pill)

Open label extension phase

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.

Group Type: OTHER

Droxidopa

Intervention Type: DRUG

Droxidopa initial dose 100mg TID, titrated in increments of 100mg every 24-48 hours to symptomatic response.

Interventions

Droxidopa

Droxidopa initial dose 100mg TID, titrated in increments of 100mg every 24-48 hours to symptomatic response.

Intervention Type: DRUG

Placebo

Placebo (sugar pill)

Intervention Type: DRUG

Other Intervention Names

Northera; Sugar pill

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lundbeck LLC

INDUSTRY

Sponsor Role: collaborator

William Ondo, MD

OTHER

Sponsor Role: lead

Responsible Party

William Ondo, MD

Principal Investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

William Ondo, MD

Role: PRINCIPAL_INVESTIGATOR

The Methodist Hospital Research Institute

Locations

Houston Methodist Hospital

Houston, Texas, United States

Countries

United States

Other Identifiers

Pro00013931

Identifier Type: -

Identifier Source: org_study_id