Norepinephrine-targeted Therapy for Action Control in Parkinson Disease
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|ClinicalTrials.gov Identifier: NCT03115827|
Recruitment Status : Completed
First Posted : April 14, 2017
Last Update Posted : February 25, 2019
|Condition or disease||Intervention/treatment||Phase|
|Parkinson Disease||Drug: Droxidopa Drug: Carbidopa||Phase 4|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||15 participants|
|Intervention Model:||Single Group Assignment|
|Intervention 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.|
|Official Title:||Norepinephrine-targeted Therapy for Action Control in Parkinson Disease|
|Actual Study Start Date :||April 18, 2017|
|Actual Primary Completion Date :||December 21, 2018|
|Actual Study Completion Date :||December 21, 2018|
Experimental: Arm 1
Droxidopa 600mg by mouth twice a day and carbidopa 200mg by mouth twice a day for 4 weeks
Droxidopa will be started at 100mg twice a day and titrated up to a maximum of 600mg twice a day
Carbidopa 200mg twice a day
- 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 ]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 patients who discontinue the study drug due to adverse effects during the 7-week treatment period. [ Time Frame: 7 weeks ]Tolerability will be defined by the number of patients who discontinue the study drug due to adverse effects.
- Maximum tolerated dose [ Time Frame: Week 4 to Week 7 ]The mean maximum tolerated dose of droxidopa reached by the study participants
- Percent compliance [ Time Frame: 7 weeks ]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 [ Time Frame: 7 weeks ]The Stop-Signal reaction time is a computerized test that assesses reaction time and response inhibition
- Change in performance on Simon task from Baseline to Week 7 [ Time Frame: 7 weeks ]The Simon task is a computerized test that assesses reaction time in the setting of irrelevant visual information.
- Change in performance on attentional blink task from Baseline to Week 7 [ Time Frame: 7 weeks ]The attentional blink task measures the ability to respond to two different stimuli presented in close temporal sequence.
- Change in gait as evaluated by GAITRite assessment from Baseline to Week 7 [ Time Frame: 7 weeks ]The GAITRite is a computerized assessment that measures several different parameters of walking and balance.
- Change in oxygen extraction on MRI from Baseline to Week 7 [ Time Frame: 7 weeks ]Measurement of the oxygen extraction fraction on MRI can be used as a surrogate for cerebral blood flow.
- Change in autonomic function parameters from Baseline to Week 7 [ Time Frame: 7 weeks ]Autonomic function tests including posture study, heart rate variability, valsalva maneuver, and blood catecholamine measurements will be performed.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03115827
|United States, Tennessee|
|Vanderbilt University Medical Center|
|Nashville, Tennessee, United States, 37232|
|Principal Investigator:||Katherine McDonell, MD||Vanderbilt Medical Center|