search
Back to results

Norepinephrine-targeted Therapy for Action Control in Parkinson Disease

Primary Purpose

Parkinson Disease

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Droxidopa
Carbidopa
Sponsored by
Vanderbilt University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Parkinson Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Nondemented man or woman 18 years of age or older with idiopathic PD based on the UK Parkinson Disease Society Brain Bank Clinical Diagnostic Criteria (refer to Appendix C for the criteria)
  2. Unified Parkinson Disease Rating Scale (UPDRS) motor scores OFF medication consistent with postural instability gait difficulty (PIGD) subtype
  3. Symptoms of freezing or falls
  4. Able to walk at least 10 meters
  5. Medically stable outpatient, based on the investigator's judgment
  6. The patient must be willing and able to give written informed consent prior to performing any study procedures.

Exclusion Criteria:

  1. Score of 21 or lower on Montreal Cognitive Assessment
  2. Sustained supine hypertension greater than or equal to 180 mmHg systolic or 110 mmHg diastolic, or have these measurements at their Baseline Visit (Visit 2). Sustained is defined as measurements persistently greater at 2 separate measurements at least 10 minutes apart with the subject supine and at rest for at least 5 minutes.
  3. Concomitant use of vasoconstricting agents such as ephedrine, dihydroergotamine, or midodrine. Concomitant use of other noradrenergic medications, such as serotonin-norepinephrine reuptake inhibitors (SNRI's) is also contraindicated. Patients must stop taking these drugs at least 2 days or 5 half-lives (whichever is longer) prior to their baseline visit and throughout the duration of the study.
  4. Diagnosis of hypertension that requires treatment with antihypertensive medications (short-acting antihypertensives to treat nocturnal supine hypertension are allowed in this study)
  5. Women of childbearing potential
  6. Any significant uncontrolled cardiac arrhythmia
  7. History of myocardial infarction, within the past 2 years
  8. Current unstable angina
  9. Congestive heart failure (NYHA Class 3 or 4)
  10. History of cancer within the past 2 years other than a successfully treated, non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer in situ
  11. History of stroke
  12. Gastrointestinal condition that may affect the absorption of study drug (e.g., ulcerative colitis, gastric bypass)
  13. Musculoskeletal disorders such as severe arthritis, post knee surgery, hip surgery, or any other condition that the investigators determine may impair assessment of gait
  14. History of myocardial infarction, uncontrolled cardiac arrhythmia, unstable angina, congestive heart failure, or stroke
  15. Untreated closed angle glaucoma
  16. Musculoskeletal or other disorders that may impair assessment of gait
  17. Any major surgical procedure within 30 days prior to the Baseline visit
  18. Previously treated with droxidopa within 30 days prior to the Baseline visit
  19. Currently receiving any other investigational drug or have received an investigational drug within 60 days prior to the Baseline visit
  20. Known or suspected alcohol or substance abuse within the past 12 months (DSM-IV definition of alcohol or substance abuse)
  21. Any condition or laboratory test result, which in the Investigator's judgment, might result in an increased risk to the patient, or would affect their participation in the study.

Sites / Locations

  • Vanderbilt University Medical Center

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Arm 1

Arm Description

Droxidopa 600mg by mouth twice a day and carbidopa 200mg by mouth twice a day for 4 weeks

Outcomes

Primary Outcome Measures

Number of Subjects Who Develop an Adverse Event During the 7-week Treatment Period That is Determined to be Likely Related to the Study Medications.
Safety will be defined by the percent of subjects who develop an adverse event during the 7-week treatment period that is determined to be likely related to the study medications.
Number of Participants Who Discontinue the Study Drug Due to Adverse Effects During the 7-week Treatment Period.
Tolerability will be defined by the number of patients who discontinue the study drug due to adverse effects.

Secondary Outcome Measures

Maximum Tolerated Dose
The mean maximum tolerated dose of droxidopa reached by the study participants
Percent Compliance
Percent compliance is defined as the percent of study participants who take greater than or equal to 70% of the assigned dosage
Change in Stop-Signal Reaction Time From Baseline to Week 7
The Stop-Signal reaction time is a computerized test that assesses reaction time and response inhibition

Full Information

First Posted
March 9, 2017
Last Updated
January 14, 2020
Sponsor
Vanderbilt University Medical Center
Collaborators
H. Lundbeck A/S, American Academy of Neurology
search

1. Study Identification

Unique Protocol Identification Number
NCT03115827
Brief Title
Norepinephrine-targeted Therapy for Action Control in Parkinson Disease
Official Title
Norepinephrine-targeted Therapy for Action Control in Parkinson Disease
Study Type
Interventional

2. Study Status

Record Verification Date
January 2020
Overall Recruitment Status
Completed
Study Start Date
April 18, 2017 (Actual)
Primary Completion Date
December 21, 2018 (Actual)
Study Completion Date
December 21, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Vanderbilt University Medical Center
Collaborators
H. Lundbeck A/S, American Academy of Neurology

4. Oversight

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
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
The purpose of this study is to find out whether droxidopa, a medication that increases norepinephrine levels, may be effective in improving some aspects of cognition and movement in Parkinson's disease (PD).
Detailed Description
Parkinson's disease (PD) is a progressive neurodegenerative disorder that affects 1 million people in the United States. PD causes a variety of disabling symptoms, which impact movement as well as cognition. Historically, we have relied on medications that increase dopamine levels to treat PD, although we are recognizing more and more that other chemicals in the brain are involved in PD as well. Droxidopa (Northera) is an approved drug for the treatment of low blood pressure in PD. It is a norepinephrine precursor, which is converted in the body to the neurotransmitter norepinephrine. This is a chemical that the body normally makes that has a variety of important activities in the brain and peripheral nervous system. In PD, the cells that make norepinephrine die off as part of the disease process. Therefore, people with PD often have low levels of norepinephrine in their blood and in their spinal fluid. Norepinephrine is important for maintaining blood pressure, which may be one reason that some people with PD have problems with their blood pressure falling too low when they stand up. This can lead to symptoms such as dizziness, lightheadedness, feeling faint, or sometimes passing out. Droxidopa has been approved by the FDA for the treatment of low blood pressure in Parkinson's disease. However, as norepinephrine is also important for a lot of processes that happen in the brain as well, we believe that this medication may be also helpful for some of the other symptoms of PD. In particular, norepinephrine plays a key role in brain networks that are important for attention, decision making, and controlling movements and actions. In order for norepinephrine to reach the brain, it must cross the blood-brain barrier. Therefore, in this study we will be giving droxidopa along with carbidopa, which stops your body from breaking down norepinephrine in the blood stream and allows it to get into the brain. This is a medication that is often given in Parkinson's disease along with levodopa in the form of carbidopa-levodopa, or Sinemet. This medication works the same way with levodopa in helping it get into the brain and improve the symptoms of PD. The only difference is that levodopa works like the chemical dopamine, whereas droxidopa works like norepinephrine. Up to this point, we have not had a way to correct the low norepinephrine levels in Parkinson's disease. Therefore, this study gives us the chance to investigate the effectiveness of a potential new treatment for PD patients.

6. Conditions and Keywords

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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Model Description
This is a single-arm study enrolling 15 patients that will all receive the experimental treatment.
Masking
None (Open Label)
Masking Description
All patients will receive the same treatment.
Allocation
N/A
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Arm 1
Arm Type
Experimental
Arm Description
Droxidopa 600mg by mouth twice a day and carbidopa 200mg by mouth twice a day for 4 weeks
Intervention Type
Drug
Intervention Name(s)
Droxidopa
Intervention Description
Droxidopa will be started at 100mg twice a day and titrated up to a maximum of 600mg twice a day
Intervention Type
Drug
Intervention Name(s)
Carbidopa
Intervention Description
Carbidopa 200mg twice a day
Primary Outcome Measure Information:
Title
Number of Subjects Who Develop an Adverse Event During the 7-week Treatment Period That is Determined to be Likely Related to the Study Medications.
Description
Safety will be defined by the percent of subjects who develop an adverse event during the 7-week treatment period that is determined to be likely related to the study medications.
Time Frame
7 weeks
Title
Number of Participants Who Discontinue the Study Drug Due to Adverse Effects During the 7-week Treatment Period.
Description
Tolerability will be defined by the number of patients who discontinue the study drug due to adverse effects.
Time Frame
7 weeks
Secondary Outcome Measure Information:
Title
Maximum Tolerated Dose
Description
The mean maximum tolerated dose of droxidopa reached by the study participants
Time Frame
Week 4 to Week 7
Title
Percent Compliance
Description
Percent compliance is defined as the percent of study participants who take greater than or equal to 70% of the assigned dosage
Time Frame
7 weeks
Title
Change in Stop-Signal Reaction Time From Baseline to Week 7
Description
The Stop-Signal reaction time is a computerized test that assesses reaction time and response inhibition
Time Frame
baseline and week 7

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Nondemented man or woman 18 years of age or older with idiopathic PD based on the UK Parkinson Disease Society Brain Bank Clinical Diagnostic Criteria (refer to Appendix C for the criteria) Unified Parkinson Disease Rating Scale (UPDRS) motor scores OFF medication consistent with postural instability gait difficulty (PIGD) subtype Symptoms of freezing or falls Able to walk at least 10 meters Medically stable outpatient, based on the investigator's judgment The patient must be willing and able to give written informed consent prior to performing any study procedures. Exclusion Criteria: Score of 21 or lower on Montreal Cognitive Assessment Sustained supine hypertension greater than or equal to 180 mmHg systolic or 110 mmHg diastolic, or have these measurements at their Baseline Visit (Visit 2). Sustained is defined as measurements persistently greater at 2 separate measurements at least 10 minutes apart with the subject supine and at rest for at least 5 minutes. Concomitant use of vasoconstricting agents such as ephedrine, dihydroergotamine, or midodrine. Concomitant use of other noradrenergic medications, such as serotonin-norepinephrine reuptake inhibitors (SNRI's) is also contraindicated. Patients must stop taking these drugs at least 2 days or 5 half-lives (whichever is longer) prior to their baseline visit and throughout the duration of the study. Diagnosis of hypertension that requires treatment with antihypertensive medications (short-acting antihypertensives to treat nocturnal supine hypertension are allowed in this study) Women of childbearing potential Any significant uncontrolled cardiac arrhythmia History of myocardial infarction, within the past 2 years Current unstable angina Congestive heart failure (NYHA Class 3 or 4) History of cancer within the past 2 years other than a successfully treated, non-metastatic cutaneous squamous cell or basal cell carcinoma or cervical cancer in situ History of stroke Gastrointestinal condition that may affect the absorption of study drug (e.g., ulcerative colitis, gastric bypass) Musculoskeletal disorders such as severe arthritis, post knee surgery, hip surgery, or any other condition that the investigators determine may impair assessment of gait History of myocardial infarction, uncontrolled cardiac arrhythmia, unstable angina, congestive heart failure, or stroke Untreated closed angle glaucoma Musculoskeletal or other disorders that may impair assessment of gait Any major surgical procedure within 30 days prior to the Baseline visit Previously treated with droxidopa within 30 days prior to the Baseline visit Currently receiving any other investigational drug or have received an investigational drug within 60 days prior to the Baseline visit Known or suspected alcohol or substance abuse within the past 12 months (DSM-IV definition of alcohol or substance abuse) Any condition or laboratory test result, which in the Investigator's judgment, might result in an increased risk to the patient, or would affect their participation in the study.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Katherine McDonell, MD
Organizational Affiliation
Vanderbilt Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Vanderbilt University Medical Center
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37232
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Norepinephrine-targeted Therapy for Action Control in Parkinson Disease

We'll reach out to this number within 24 hrs