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

• ClinicalTrials.gov Identifier: NCT03567447
• Recruitment Status: Unknown
• First Posted: June 25, 2018
• Last Update Posted: October 29, 2019
• Sponsor: St. Joseph's Hospital and Medical Center, Phoenix
• Collaborators: H. Lundbeck A/S; Arizona State University
• Information provided by (Responsible Party): St. Joseph's Hospital and Medical Center, Phoenix

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Parkinson Disease; Falls Patient	Drug: Droxidopa; Other: Placebo	Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 10 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Phase II single center, double-blind, randomized, placebo-controlled, efficacy study
• Masking: Triple (Participant, Investigator, Outcomes Assessor)
• Masking Description: Double blind masking
• Primary Purpose: Treatment
• Official Title: Effect of L-Dihydroxyphenylserine (L-DOPS) on Falls in Patients With Neurogenic Orthostatic Hypotension (NOH)
• Actual Study Start Date: August 17, 2018
• Estimated Primary Completion Date: December 1, 2019
• Estimated Study Completion Date: March 1, 2020

Arms and Interventions

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 Name: 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.

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

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

Eligibility Criteria

• Ages Eligible for Study: 30 Years to 83 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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

Contacts and Locations

Contacts

Contact: Margaret McCauley; 602-406-8134; Margaret.McCauley@dignityhealth.org

Contact: Pam Dewey; 602-406-8252; pam.dewey@dignityhealth.org

Locations

United States, Arizona

Barrow Neurological Institute at St. Joseph's Hospital and Medical Center; Recruiting

Phoenix, Arizona, United States, 85013

Contact: Margaret McCauley, RN 602-406-8134

Sponsors and Collaborators

St. Joseph's Hospital and Medical Center, Phoenix

H. Lundbeck A/S

Arizona State University

Investigators

• Principal Investigator: Abraham Lieberman, MD; Barrow Neurological Insitute

More Information

• Responsible Party: St. Joseph's Hospital and Medical Center, Phoenix
• ClinicalTrials.gov Identifier: NCT03567447
• Other Study ID Numbers: 16-0200-80-04
• First Posted: June 25, 2018
• Last Update Posted: October 29, 2019
• Last Verified: October 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by St. Joseph's Hospital and Medical Center, Phoenix:

Parkinsons Disease; PD; Patient Falls; Neurogenic Orthostatic Hypotension

Additional relevant MeSH terms:

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