Parkinson DiseasePhase 4NCT03115827
Norepinephrine-targeted Therapy for Action Control in Parkinson Disease
A Phase 4 study testing Droxidopa and Carbidopa in people with Parkinson Disease, run by Vanderbilt University Medical Center at 1 site in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Parkinson Disease
- What is being tested?
- Droxidopa and Carbidopa
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Apr 2017to 21 Dec 2018
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 21Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Vanderbilt University Medical Center
Nashville, Tennessee, 37232
About this study
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).
Read the 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.
- Conditions
- Parkinson Disease
- Being tested
- Droxidopa, Carbidopa
- Medical subject headings
- Parkinson Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DroxidopaDrug
Droxidopa will be started at 100mg twice a day and titrated up to a maximum of 600mg twice a day
CarbidopaDrug
Carbidopa 200mg twice a day
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Experimental | Droxidopa 600mg by mouth twice a day and carbidopa 200mg by mouth twice a day for 4 weeks Receives: Drug: Droxidopa; Drug: Carbidopa |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7 weeks
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.
Measured: 7 weeks
Secondary outcomes (3)
Maximum Tolerated Dose
The mean maximum tolerated dose of droxidopa reached by the study participants
Measured: Week 4 to Week 7
Percent Compliance
Percent compliance is defined as the percent of study participants who take greater than or equal to 70% of the assigned dosage
Measured: 7 weeks
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
Measured: baseline and week 7
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2017
- Study start18 Apr 2017
- Primary completion21 Dec 2018
- Study completion21 Dec 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Parkinson DiseaseStudies of the same condition, open and under way.
- More trials run by Vanderbilt University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a single-arm study enrolling 15 patients that will all receive the experimental treatment.
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- H. Lundbeck A/S, American Academy of Neurology
- Responsible party
- Principal investigator, Katherine Eder McDonell, Vanderbilt University Medical Center
- Investigators
- Katherine McDonell, MD, Principal investigator, Vanderbilt Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03115827
- Sponsor's protocol ID
- VUMC54580
- Status last verified
- Jan 2020
- First submitted
- 9 Mar 2017
- Last updated
- 27 Jan 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Norepinephrine-targeted Therapy for Action Control in Parkinson Disease
- ClinicalTrials.gov ID
- NCT03115827
- Acronym / sponsor ID
- VUMC54580
- Conditions
- Parkinson Disease
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Vanderbilt University Medical CenterUniversity, hospital or other
- Collaborators
- H. Lundbeck A/S, American Academy of Neurology
- Study start
- 18 Apr 2017 (actual)
- Primary completion
- 21 Dec 2018 (actual)
- Study completion
- 21 Dec 2018 (actual)
- First posted
- 14 Apr 2017 (actual)
- Results
- Posted 27 Jan 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a single-arm study enrolling 15 patients that will all receive the experimental treatment.
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Experimental | Drug: Droxidopa, Drug: CarbidopaDroxidopa 600mg by mouth twice a day and carbidopa 200mg by mouth twice a day for 4 weeks |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (21 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| DroxidopaDroxidopa will be started at 100mg twice a day and titrated up to a maximum of 600mg twice a day | Drug | Arm 1 |
| CarbidopaCarbidopa 200mg twice a day | Drug | Arm 1 |
Primary outcome
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.
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 Participants 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.
3 secondary outcomes
Maximum Tolerated Dose
Time frame: Week 4 to Week 7
Percent Compliance
Time frame: 7 weeks
Change in Stop-Signal Reaction Time From Baseline to Week 7
Time frame: baseline and week 7
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Katherine McDonell, MD principal investigator
Vanderbilt Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Droxidopa and Carbidopa in people with Parkinson Disease, run by Vanderbilt University Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 27 Jan 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 27 Jan 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 7 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2020.