Effect of L-Dihydoxyphenylserine on Locomotion, Postural Stability, and Fall Risk Reduction in Parkinson Disease

NCT02812147 | Unknown Phase 2

• 1 other identifier: PHX15BN108
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

This research study is being done to determine whether treatment with L- Dihydroxyphenylserine (L-DOPS) versus placebo (an inactive substance that looks like study drug) in addition to other Parkinson Disease (PD) drugs will improve balance, walking, and reduce risk of falls and/or severity of falls in PD subjects. The study is also being done to determine the effectiveness, safety, and tolerability of L-DOPS, and whether it will decrease Freezing of Gait (FOG), improve apathy (generalized disinterest) or show a relationship between apathy and slowed movement and fall risk.

Conditions

Parkinson Disease

Keywords

L-dihydoxyphenylserine; L-DOPS; Northera

Outcome Measures

Primary Outcomes (5)

• Motor Score

  Measured with United Parkinson's Disease Rating Scale (Part III 0-45) in the medication state of "on", "off", or both.

  4 months

• Balance Score

  Measured using Barrow Neurologic Institute (BNI) Balance Scale 0-20, in the medication state of "on", "off", or both.

  4 months

• Postural Stability

  Measured using a NeuroCom Equitest System, which tests sensory organization, motor control time, and postural sway measures, in the medication state of "on", "off", or both.

  4 months

• Dynamic Stability

  Dynamic stability is measured by wearable devices (Inertial Measurement Units) that collect gait parameters during gait and postural transitions,in the medication state of "on", "off", or both.

  4 months

• Falls

  Incidence of falls is self-report, in the medication state of "on", "off", or both.

  4 months

Secondary Outcomes (3)

• Freezing of Gait (FOG)

  4 months

• Apathy

  4 months

• Orthostatic Hypotension

  4 months

Study Arms (2)

L-DOPS

ACTIVE COMPARATOR

All participants will be on levodopa/carbidopa, and may be on additional dopaminergic drugs including dopamine agonists and/or monoamine type B oxidase inhibitors or amantadine. L-dihydoxyphenylserine will be added, administered as an oral capsule 3 times a day for 4 months. Dosing will begin at 100 mg of L-DOPS three times per day and titrated upward, by 100 mg three times a day, as tolerated. Tolerability will be evaluated based upon questionnaires, patient interviews, vital signs and investigator examination. In order to participate in the study, all subjects must be able to tolerate a minimum tolerated dose of 400 mg three times per day (1200mg/day). Subject maximum dose will be 600 mg three times per day (1800mg/day). Patients will be maintained on this dose for 4 months (until the cross-over). After a 7-day washout, participants will cross over to the Placebo arm.

Drug: L-DOPS

Placebo

PLACEBO COMPARATOR

All participants will be on levodopa/carbidopa, and may be on additional dopaminergic drugs including dopamine agonists and/or monoamine type B oxidase inhibitors or amantadine. Placebo will be added, administered as an oral capsule 3 times a day for 4 months. Dosing will begin at 100 mg of placebo three times per day and titrated upward, by 100 mg three times a day, as tolerated. Tolerability will be evaluated based upon questionnaires, patient interviews, vital signs and investigator examination. In order to participate in the study, all subjects must be able to tolerate a minimum tolerated dose of 400 mg three times per day (1200mg/day). Subject maximum dose will be 600 mg three times per day (1800mg/day). Patients will be maintained on this dose for 4 months (until the cross-over) After a 7-day washout, participants will cross over to the L-DOPS arm.

Drug: Placebo

Interventions

L-DOPS DRUG

Added as described in the Arm/Group Descriptions.

Also known as: L-dihydoxyphenylserine, Northera

L-DOPS

Placebo DRUG

Added as described in the Arm/Group Descriptions.dded as described in the Arm/Group Descriptions.

Also known as: sugar pill

Placebo

Eligibility Criteria

• Age: 30 Years - 83 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subject has voluntarily signed and dated an informed consent form (ICF) prior to any participation in the study.
• Hoehn and Yahr Stage II, III, IV in an "on" state.
• Fell more than twice in past year.
• Montreal Cognitive Assessment (MOCA) score ≥ 24.
• Stable dose of levodopa, dopamine agonist, amantadine, and/or monoamine oxidase B inhibitor, i.e. unchanged for 3 months.
• Subject is ambulatory and able to walk ≥ 10 meters with/without the use of an assistive device.

You may not qualify if:

• Patients with atypical Parkinson disorders that result in a high number of falls.These disorders include: Progressive Supranuclear Palsy (PSP), Multiple System Atrophy (MSA), Primary Freezing of Gait (PFG), and Corticobasal Degeneration.
• Patients with dementia MOCA ≤ 23.
• Patients with symptomatic Orthostatic Hypotension being treated with midodrine, fludrocortisone or L-DOPS.
• Patients with uncontrolled hypertension.
• Patients with known allergies to L-DOPS or its excipients.
• Patients with major orthopedic problems of their hips or knees, and patients who need hip or knee replacements.
• Patient with schizophrenia, a schizo-affective disorder, or a bipolar disorder.
• Patients with hallucinations, psychoses, or delusions.
• Patients with a history of recent stroke or myocardial infarction.

Sponsors & Collaborators

• St. Joseph's Hospital and Medical Center, Phoenix: lead
• Arizona State University: collaborator

Study Sites (1)

Barrow Neurological Institute/St. Joseph's Hospital and Medical Center

Phoenix, Arizona, 85013, United States

Location

MeSH Terms

Conditions

Parkinson Disease

Interventions

Droxidopa; Sugars

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Norepinephrine; Catecholamines; Amines; Organic Chemicals; Catechols; Phenols; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Serine; Amino Acids, Neutral; Amino Acids; Amino Acids, Peptides, and Proteins; Carbohydrates

Study Officials

• Abraham Lieberman, MD

  Barrow Neurological Institute/St. Joseph's Hospital and Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Manager

Study Record Dates

• First Submitted: May 25, 2016
• First Posted: June 24, 2016
• Study Start: May 1, 2016
• Primary Completion: June 1, 2019
• Study Completion: June 1, 2019
• Last Updated: February 15, 2019

Record last verified: 2019-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)