ClinicalTrials.gov
ClinicalTrials.gov Menu

Brain Perfusion & Oxygenation in Parkinson's Disease With NOH

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03229174
Recruitment Status : Not yet recruiting
First Posted : July 25, 2017
Last Update Posted : July 25, 2017
Sponsor:
Collaborator:
Lundbeck LLC
Information provided by (Responsible Party):
William Ondo, MD, The Methodist Hospital System

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.

Condition or disease Intervention/treatment Phase
Parkinson Disease Neurogenic Orthostatic Hypotension Drug: Droxidopa Drug: Placebo Phase 4

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.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 28 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Official Title: Evaluation of Brain Perfusion and Oxygenation in PD Patients With Neurogenic Orthostatic Hypotension: 4 Week Comparison of Droxidopa Versus Placebo
Estimated Study Start Date : September 1, 2017
Estimated Primary Completion Date : April 2018
Estimated Study Completion Date : September 2018


Arm Intervention/treatment
Experimental: 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
Drug: Droxidopa
Droxidopa initial dose 100mg TID, titrated in increments of 100mg every 24-48 hours to symptomatic response.
Other Name: Northera

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




Primary Outcome Measures :
  1. Cerebral perfusion [ Time Frame: 8 weeks ]
    Cerebral perfusion measured by trans-cranial ultrasound of middle cerebral artery "supine and standing" delta.

  2. Brain oxygenation [ Time Frame: 8 weeks ]
    Brain oxygenation as measured by cerebral pulse oximetry device, delta between supine and standing


Secondary Outcome Measures :
  1. Arteriole Blood Pressure [ Time Frame: 8 weeks ]
    Change in arteriole BP (supine/standing) via tilt table

  2. R-R variability [ Time Frame: 8 weeks ]
    changes in autonomic influence on heart rate placebo vs drug

  3. Orthostatic hypotension [ Time Frame: 8 weeks ]
    Orthostatic hypotension scale

  4. Assessment of Parkinson's disease symptoms [ Time Frame: 8 weeks ]
    Movement disorder society- Unified parkinson disease rating scale (MDS-UPDRS)

  5. Assessment of gait and falls [ Time Frame: 8 weeks ]
    Timed Up and Go test


Other Outcome Measures:
  1. Assessment of depressive symptoms [ Time Frame: 8 weeks ]
    Beck Depression Inventory

  2. Assessment of sleepiness [ Time Frame: 8 weeks ]
    Epworth sleepiness scale (ESS)

  3. Assessment of cognitive changes [ Time Frame: 8 weeks ]
    Montreal cognitive assessment (MOCA)

  4. Assessment of fatigue [ Time Frame: 8 weeks ]
    Fatigue severity scale (FSS)

  5. Participant impression of light-headedness [ Time Frame: 8 weeks ]
    Subjective assessment of "light-headedness"



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 85 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03229174


Contacts
Contact: William Ondo, MD 713-363-8184 wondo@houstonmethodist.org
Contact: Titilayo Olubajo 713-363-8390 tolubajo@houstonmethodist.org

Sponsors and Collaborators
William Ondo, MD
Lundbeck LLC
Investigators
Principal Investigator: William Ondo, MD The Methodist Hospital System

Responsible Party: William Ondo, MD, Sponsor-Investigator, Principal Investigator, The Methodist Hospital System
ClinicalTrials.gov Identifier: NCT03229174     History of Changes
Other Study ID Numbers: Pro00013931
First Posted: July 25, 2017    Key Record Dates
Last Update Posted: July 25, 2017
Last Verified: July 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Parkinson Disease
Hypotension
Hypotension, Orthostatic
Parkinsonian Disorders
Basal Ganglia Diseases
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Movement Disorders
Neurodegenerative Diseases
Vascular Diseases
Cardiovascular Diseases
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Droxidopa
Antiparkinson Agents
Anti-Dyskinesia Agents