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

Primary Purpose

Parkinson Disease, Falls Patient

Status

Unknown status

Phase

Phase 2

Locations

United States

Study Type

Interventional

Intervention

Droxidopa

Placebo

About this trial

This is an interventional treatment trial for Parkinson Disease focused on measuring Parkinsons Disease, PD, Patient Falls, Neurogenic Orthostatic Hypotension

Eligibility Criteria

30 Years - 83 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

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.
Subject is male or female and is ≥ 30 and ≤ 83 years of age.
Parkinson's diagnosis with history of falls or gait difficulty.
Subject demonstrates neurogenic orthostatic hypotension (drop of 20 mm/Hg Systolic or 10 mm/Hg diastolic or both within 3 min of standing)
Fell more than once in past year.
Montreal Cognitive Assessment (MoCA) score ≥ 21.
Stable dose of levodopa, dopamine agonist, amantadine, and/or monoamine oxidase B inhibitor, i.e. unchanged for 1 month.
Subject is ambulatory and able to walk ≥ 10 meters with/without the use of an assistive device.

Exclusion Criteria:

Subject has a clinical diagnosis of an atypical Parkinsonism
Subject has a clinical diagnosis of PD that is suspicious to the investigator as being a possible case of atypical Parkinson's
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
Patients with systolic BP ≤70 mm/hg
Subjects with a history of coronary artery disease or congestive heart failure
Participation in another investigational drug or device study in during the 60 days prior to the Screening Visit
Treatment with any anti-hypertensive medications
Treatment with any anti-spasmodic medications
Treatment with medications intended to elevate blood pressure
Treatment with non-specific monoamine oxidase (MAO) inhibitors

Sites / Locations

Barrow Neurological Institute at St. Joseph's Hospital and Medical CenterRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Treatment group

Non treatment group

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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)

Full Information

NCT ID

NCT03567447

First Posted

May 21, 2018

Last Updated

October 25, 2019

Sponsor

St. Joseph's Hospital and Medical Center, Phoenix

Collaborators

H. Lundbeck A/S, Arizona State University

1. Study Identification

Unique Protocol Identification Number

NCT03567447

Brief Title

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

Official Title

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

Study Type

Interventional

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Unknown status

Study Start Date

August 17, 2018 (Actual)

Primary Completion Date

December 1, 2019 (Anticipated)

Study Completion Date

March 1, 2020 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

St. Joseph's Hospital and Medical Center, Phoenix

Collaborators

H. Lundbeck A/S, Arizona State University

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Yes

Studies a U.S. FDA-regulated Device Product

Product Manufactured in and Exported from the U.S.

Data Monitoring Committee

5. 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Parkinson Disease, Falls Patient

Keywords

Parkinsons Disease, PD, Patient Falls, Neurogenic Orthostatic Hypotension

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 2

Interventional Study Model

Parallel Assignment

Model Description

Phase II single center, double-blind, randomized, placebo-controlled, efficacy study

Masking

ParticipantInvestigatorOutcomes Assessor

Masking Description

Double blind masking

Allocation

Randomized

Enrollment

10 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Treatment group

Arm Type

Experimental

Arm Description

Arm Title

Non treatment group

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Drug

Intervention Name(s)

Droxidopa

Other Intervention Name(s)

NORTHERA

Intervention Description

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.

Intervention Type

Other

Intervention Name(s)

Placebo

Intervention Description

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.

Primary Outcome Measure Information:

Title

Change in number of falls

Description

The effect of L-DOPS on falls will be assessed by measuring the number of falls during balance perturbation testing.

Time Frame

Study weeks 2, 4 and 8

Secondary Outcome Measure Information:

Title

Change in objective and subjective measures of Balance

Description

The effect of L-DOPS on assessments of balance by Movement Disorder Society- Unified Parkinson's Disease Rating Scale (MDS-UPDRS)

Time Frame

Study weeks 2, 4 and 8

10. Eligibility

Sex

All

Minimum Age & Unit of Time

30 Years

Maximum Age & Unit of Time

83 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: 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. Subject is male or female and is ≥ 30 and ≤ 83 years of age. Parkinson's diagnosis with history of falls or gait difficulty. Subject demonstrates neurogenic orthostatic hypotension (drop of 20 mm/Hg Systolic or 10 mm/Hg diastolic or both within 3 min of standing) Fell more than once in past year. Montreal Cognitive Assessment (MoCA) score ≥ 21. Stable dose of levodopa, dopamine agonist, amantadine, and/or monoamine oxidase B inhibitor, i.e. unchanged for 1 month. Subject is ambulatory and able to walk ≥ 10 meters with/without the use of an assistive device. Exclusion Criteria: Subject has a clinical diagnosis of an atypical Parkinsonism Subject has a clinical diagnosis of PD that is suspicious to the investigator as being a possible case of atypical Parkinson's 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 Patients with systolic BP ≤70 mm/hg Subjects with a history of coronary artery disease or congestive heart failure Participation in another investigational drug or device study in during the 60 days prior to the Screening Visit Treatment with any anti-hypertensive medications Treatment with any anti-spasmodic medications Treatment with medications intended to elevate blood pressure Treatment with non-specific monoamine oxidase (MAO) inhibitors

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Margaret McCauley

Phone

602-406-8134

Margaret.McCauley@dignityhealth.org

First Name & Middle Initial & Last Name or Official Title & Degree

Pam Dewey

Phone

602-406-8252

pam.dewey@dignityhealth.org

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Abraham Lieberman, MD

Organizational Affiliation

Barrow Neurological Insitute

Official's Role

Principal Investigator

Facility Information:

Facility Name

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

City

Phoenix

State/Province

Arizona

ZIP/Postal Code

85013

Country

United States

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Margaret McCauley, RN

Phone

602-406-8134

12. IPD Sharing Statement

Plan to Share IPD

Learn more about this trial

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

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