Effect of L-Dihydroxyphenylserine (L-DOPS) on Falls in Patients With Neurogenic Orthostatic Hypotension (NOH)

This will be a Phase II single center, double-blind, randomized, placebo-controlled, efficacy study. Subjects will complete six visits. The first will be a screening visit. There will be four assessment visits: baseline, 2 weeks after the double-blinded trial begins, the end of the blinded trial, and after 4 weeks of washout. There will also be an additional randomization and medication dispensing visit immediately following the dose optimization period and preceding the double-blinded trial.

Study Overview

• Status: Unknown
• Conditions: Parkinson Disease; Falls Patient
• Intervention / Treatment: Drug: Droxidopa; Other: Placebo

Detailed Description

Injuries associated with falls continue to pose a significant burden to patients with Parkinson's disease (PD) both in terms of human suffering and economic losses. Overall annual fall incidence rates range from 50-70% for PD patients, and recurrent falls are a major cause of disability in PD. Approximately 20% of patients with Parkinson's disease develop NOH which can lead to falls. Although the mechanisms underlying impaired postural stability and falls are not well-known in patients with PD, attention is focused on the noradrenergic system. L-DOPS, a drug that enhances norepinephrine levels in peripheral and central nervous system, has been shown to moderate NOH, and often improve symptoms concomitant of PD and falls.

This study will help to determine the effect of L-DOPS in reducing falls and fall severity by using an instrumented walkway to induce slip perturbations can assess the propensity for falls and fall-related outcomes. It will assess fall events from the point of initiation through recovery. The effect of L-DOPS on gait and balance parameters will also be measured using force plate and inertial measurement unit (IMU) testing, and improvement in clinical scores such as the MDS-UPDRS will be monitored.

• Study Type: Interventional
• Enrollment (Anticipated): 10
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Phoenix, Arizona, United States, 85013
      • Recruiting
      • Barrow Neurological Institute at St. Joseph's Hospital and Medical Center
      • Contact: Margaret McCauley, RN; Phone Number: 602-406-8134

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 83 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject has voluntarily signed and dated an informed consent form (ICF), approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), and provided Health Insurance Portability and Accountability Act (HIPAA) (or other applicable privacy regulation) authorization prior to any participation in the study.
2. Subject is male or female and is ≥ 30 and ≤ 83 years of age.
3. Parkinson's diagnosis with history of falls or gait difficulty.
4. Subject demonstrates neurogenic orthostatic hypotension (drop of 20 mm/Hg Systolic or 10 mm/Hg diastolic or both within 3 min of standing)
5. Fell more than once in past year.
6. Montreal Cognitive Assessment (MoCA) score ≥ 21.
7. Stable dose of levodopa, dopamine agonist, amantadine, and/or monoamine oxidase B inhibitor, i.e. unchanged for 1 month.
8. Subject is ambulatory and able to walk ≥ 10 meters with/without the use of an assistive device.

Exclusion Criteria:

1. Subject has a clinical diagnosis of an atypical Parkinsonism
2. Subject has a clinical diagnosis of PD that is suspicious to the investigator as being a possible case of atypical Parkinson's
3. History of significant psychiatric illness such as schizophrenia or bipolar affective disorder or any other significant psychiatric illness that in the opinion of the investigator would interfere with participation in the study; history of major depressive disorder in the past year, or current major depressive episode
4. Patients with systolic BP ≤70 mm/hg
5. Subjects with a history of coronary artery disease or congestive heart failure
6. Participation in another investigational drug or device study in during the 60 days prior to the Screening Visit
7. Treatment with any anti-hypertensive medications
8. Treatment with any anti-spasmodic medications
9. Treatment with medications intended to elevate blood pressure
10. Treatment with non-specific monoamine oxidase (MAO) inhibitors

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Treatment group; This group will receive droxidopa 100mg to 600mg three times a day (TID) titration for 2 weeks and then maintenance dosage for 4 additional weeks. We will assess participants two times over the 4-week intervention. Each assessment will be the same as the baseline assessment, including the Orthostatic Hypotension Symptom Assessment (OHSA), postural, and gait assessments, and will be administered during the 2nd and 4th weeks following onset of stable treatment phase.	Drug: Droxidopa; starting with 100 mg TID and increasing in 100 mg TID increments, to a maximum of 600mg TID, to identify the highest tolerated dose for each patient.; Other Names: NORTHERA; Other: Placebo; appearing to be 100 mg TID and increasing in 100 mg TID increments, to a maximum of 600mg TID, to identify the highest tolerated dose for each patient.
PLACEBO_COMPARATOR: Non treatment group; This group will receive placebo appearing to be 100mg to 600mg three times a day (TID) titration for 2 weeks and then maintenance dosage for 4 additional weeks. We will assess participants two times over the 4-week intervention. Each assessment will be the same as the baseline assessment, including the Orthostatic Hypotension Symptom Assessment (OHSA), postural, and gait assessments, and will be administered during the 2nd and 4th weeks following onset of stable treatment phase.	Other: Placebo; appearing to be 100 mg TID and increasing in 100 mg TID increments, to a maximum of 600mg TID, to identify the highest tolerated dose for each patient.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in number of falls	The effect of L-DOPS on falls will be assessed by measuring the number of falls during balance perturbation testing.	Study weeks 2, 4 and 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in objective and subjective measures of Balance	The effect of L-DOPS on assessments of balance by Movement Disorder Society- Unified Parkinson's Disease Rating Scale (MDS-UPDRS)	Study weeks 2, 4 and 8

Collaborators and Investigators

• Sponsor: St. Joseph's Hospital and Medical Center, Phoenix
• Collaborators: H. Lundbeck A/S; Arizona State University
• Investigators: Principal Investigator: Abraham Lieberman, MD, Barrow Neurological Insitute

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 17, 2018
• Primary Completion (ANTICIPATED): December 1, 2019
• Study Completion (ANTICIPATED): March 1, 2020

Study Registration Dates

• First Submitted: May 21, 2018
• First Submitted That Met QC Criteria: June 12, 2018
• First Posted (ACTUAL): June 25, 2018

Study Record Updates

• Last Update Posted (ACTUAL): October 29, 2019
• Last Update Submitted That Met QC Criteria: October 25, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: PD; Parkinsons Disease; Patient Falls; Neurogenic Orthostatic Hypotension
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Parkinsonian Disorders; Basal Ganglia Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Autonomic Nervous System Diseases; Primary Dysautonomias; Orthostatic Intolerance; Parkinson Disease; Hypotension; Hypotension, Orthostatic; Antiparkinson Agents; Anti-Dyskinesia Agents; Droxidopa
• Other Study ID Numbers: 16-0200-80-04

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• 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