Spinal Cord InjuryPhase 1NCT01354158
A Dose Titration of Droxidopa in Patients With Spinal Cord Injury
A Phase 1 study testing Droxidopa in people with Spinal Cord Injury and Hypotension, run by Bronx VA Medical Center at 1 site in United States.
Trial summary
The investigators seek to determine the efficacy, duration of action and safety of escalating dose of droxidopa on systemic blood pressure, cerebral blood flow and vasoactive hormones and catecholamines during upright seated posture. Primary Question: 1. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Spinal Cord Injury, Hypotension
- What is being tested?
- Droxidopa
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteUnited States
- Study dates
- May 2011to May 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- between the ages of 18 and 65,
- diagnosed with hypotension as defined above,
- able to provide informed consent
Who cannot join
- Known or suspected sensitivity to study medication or any of its ingredients,
- current smoker,
- known coronary heart and/or artery disease,
- hypertension,
- diabetes mellitus or insipidus,
- thyroid disease,
Show all 21Show fewer
- closed angle glaucoma,
- acute illness,
- major surgery in the last 30 days,
- renal diseases,
- pregnancy,
- recent history (within the past year) of cocaine use,
- tricyclic antidepressants, monoamine oxidase inhibitors, and catechol-O-methyltransferase inhibitors,
- currently taking vasoconstricting medicines, such as Midodrine, ephedrine, dihydroergotamine, and the triptan class of migraine drugs,
- Use of a halogen based anesthetic such as Halothane in the past 12 hours
- Currently taking Isoproterenol and other catecholamine preparations
- Peripheral Arterial Disease,
- Abdominal Aortic Aneurysm,
- Cerebrovascular Disease (Including prior CVA or TIA),
- History of or active Congestive Heart Failure,
- Known Systolic Dysfunction
Trial locations and contacts
1 site in 1 country.
United States1 site
James J. Peters VA Medical Center
The Bronx, New York, 10468
About this study
Official title: A Dose Response Trial of Droxidopa to Treat Hypotension in Persons With SCI
The investigators seek to determine the efficacy, duration of action and safety of escalating dose of droxidopa on systemic blood pressure, cerebral blood flow and vasoactive hormones and catecholamines during upright seated posture.
Primary Question:
Read more
- What is the lowest dose of droxidopa that increases seated SBP to 115±5 mmHg in men and 105±5 mmHg in women?
- When does the defined increase in SBP occur after oral ingestion of droxidopa?
- How long does this dose of droxidopa sustain SBP at these levels?
- What are the vital signs and the subjective symptomology following droxidopa administration?
Secondary Question:
- What is the MFV response to droxidopa administration in hypotensive individuals with SCI?
- Does an increase in SBP correspond to an increase in MCA MFV?
Tertiary Question:
- What is the vasoactive hormone and catecholamine response to droxidopa administration in hypotensive individuals with SCI?
- Does droxidopa administration result in a change in APR, Aldo or NE in hypotensive individuals with SCI?
Read the detailed description
Persons with spinal cord injury (SCI), due to partial to complete interruption of sympathetic pathways from the brainstem to the cardiovascular system are prone to blood pressure dysregulation including hypotension which is worsened during orthostasis. It is well established that orthostatic hypotension (OH) hinders the rehabilitation process during the acute phase of SCI but also may hamper the resumption of independence and activity in persons with chronic SCI. Surprisingly, only a few reports exist on the use and efficacy of an alpha receptor agonist (midodrine hydrochloride) to restore blood pressure to more normal levels in persons with tetraplegia. Our group has recently reported normalization of supine blood pressure with a relatively low dose of the nitric oxide synthase inhibitor (NOSi), nitro-L-arginine methyl ester (L-NAME). In addition to an alpha agonist and a NOSi, the use of a norepinephrine (NE) precursor, droxidopa, may be safe and efficacious for the treatment of orthostatic hypotension in a human model of SCI.
It has been demonstrated that the blood pressure-raising effect of 3,4-threo-dihydroxyphenylserine (droxidopa) occurs independently of the central nervous system in human models of neurologic OH by conversion to norepinephrine (NE) in neuronal and non-neuronal tissue. Oral droxidopa is taken up by the more peripheral sympathetic neurons, converted to NE, stored and released appropriately during postural stress. Droxidopa has been used for the effective treatment of OH in several human models of neurologically caused autonomic disorders, such as familial amyloid polyneuropathy, autoimmune autonomic neuropathy, pure autonomic failure, and multiple system atrophy . The effectiveness of droxidopa at improving orthostatic blood pressure in persons with SCI has not been studied. To date, only a single case on the use of the drug in a person with SCI has been reported and the use droxidopa in that case was successful. The purpose of this proposal is to determine the dose effectiveness, duration of action and any adverse events following droxidopa administration in hypotensive individuals with SCI.
To determine the efficacy, duration of action and safety of escalating dose of droxidopa on systemic blood pressure, cerebral blood flow and vasoactive hormones and catecholamines during upright seated posture.
Primary Question:
- What is the lowest dose of droxidopa that increases seated SBP to 115±5 mmHg in men and 105±5 mmHg in women?
- When does the defined increase in SBP occur after oral ingestion of droxidopa?
- How long does this dose of droxidopa sustain SBP at these levels?
- What are the vital signs and the subjective symptomology following droxidopa administration?
Secondary Question:
- What is the MFV response to droxidopa administration in hypotensive individuals with SCI?
- Does an increase in SBP correspond to an increase in MCA MFV?
Tertiary Question:
- What is the vasoactive hormone and catecholamine response to droxidopa administration in hypotensive individuals with SCI?
- Does droxidopa administration result in a change in APR, Aldo or NE in hypotensive individuals with SCI?
- Conditions
- Spinal Cord Injury, Hypotension
- Being tested
- Droxidopa
- Medical subject headings
- Spinal Cord Injuries, Hypotension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DroxidopaDrug
Also called L-DOPs
Dose titration of placebo, 100mg, 200mg, 400mg of Droxidopa will be given to assess the effects of Droxidopa on blood pressure and cerebral blood flow.
| Study group | Role | What they receive |
|---|---|---|
| Droxidopa | Experimental | The dose-titration response to ascending doses of Droxidopa (placebo, 100mg, 200mg, 400mg) will be measured four separate days. Receives: Drug: Droxidopa |
What is being measured
The primary outcome is the main question the study is designed to answer.
The lowest dose of droxidopa that increases seated SBP to 115±5 mmHg in men and 105±5 mmHg in women
4 day titration of Droxidopa (placebo day 1, 100mg day 2, 200mg day 3, 400mg day). Blood pressure will be collected at the arm and finger (photoplethysmography) in 15 minute intervals during the duration of the protocol (approximately six hours). The subject will also wear a 24 hour portable arm blood pressure cuff, to assess the effect of Droxidopa on blood pressure 24 hrs post intervention.
Measured: 4 days
Secondary outcomes (2)
The MFV response to droxidopa administration in hypotensive individuals with SCI
MFV will be measured each day at distinct time points to track cerebral blood flow during Droxidopa administration.
Measured: 4 days
To assess the vasoactive hormone and catecholamine response to droxidopa administration in hypotensive individuals with SCI
The catecholamine response to Droxidopa will be measured a total of 6 times throughout each study day by antecubital venipuncture.
Measured: 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 May 2011 (estimated)
- Study startMay 2011
- Primary completionMay 2013
- Study completionMay 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Spinal Cord InjuryStudies of the same condition, open and under way.
- 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 1
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bronx VA Medical Center
- Sponsor type
- US federal agency
- Collaborators
- Chelsea Therapeutics
- Investigators
- Jill M Wecht, EdD, Principal investigator, James J. Peters VA Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01354158
- Sponsor's protocol ID
- 01272
- Status last verified
- May 2011
- First submitted
- 12 May 2011
- Last updated
- 30 Jul 2013
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 30 Jul 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Response Trial of Droxidopa to Treat Hypotension in Persons With SCI
- ClinicalTrials.gov ID
- NCT01354158
- Acronym / sponsor ID
- 01272
- Conditions
- Spinal Cord Injury, Hypotension
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Bronx VA Medical CenterUS federal agency
- Collaborators
- Chelsea Therapeutics
- Study start
- May 2011
- Primary completion
- May 2013 (actual)
- Study completion
- May 2013 (actual)
- First posted
- 16 May 2011 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The investigators seek to determine the efficacy, duration of action and safety of escalating dose of droxidopa on systemic blood pressure, cerebral blood flow and vasoactive hormones and catecholamines during upright seated posture.
Primary Question:
- What is the lowest dose of droxidopa that increases seated SBP to 115±5 mmHg in men and 105±5 mmHg in women?
- When does the defined increase in SBP occur after oral ingestion of droxidopa?
- How long does this dose of droxidopa sustain SBP at these levels?
- What are the vital signs and the subjective symptomology following droxidopa administration?
Secondary Question:
- What is the MFV response to droxidopa administration in hypotensive individuals with SCI?
- Does an increase in SBP correspond to an increase in MCA MFV?
Tertiary Question:
- What is the vasoactive hormone and catecholamine response to droxidopa administration in hypotensive individuals with SCI?
- Does droxidopa administration result in a change in APR, Aldo or NE in hypotensive individuals with SCI?
Detailed description
Persons with spinal cord injury (SCI), due to partial to complete interruption of sympathetic pathways from the brainstem to the cardiovascular system are prone to blood pressure dysregulation including hypotension which is worsened during orthostasis. It is well established that orthostatic hypotension (OH) hinders the rehabilitation process during the acute phase of SCI but also may hamper the resumption of independence and activity in persons with chronic SCI. Surprisingly, only a few reports exist on the use and efficacy of an alpha receptor agonist (midodrine hydrochloride) to restore blood pressure to more normal levels in persons with tetraplegia. Our group has recently reported normalization of supine blood pressure with a relatively low dose of the nitric oxide synthase inhibitor (NOSi), nitro-L-arginine methyl ester (L-NAME). In addition to an alpha agonist and a NOSi, the use of a norepinephrine (NE) precursor, droxidopa, may be safe and efficacious for the treatment of orthostatic hypotension in a human model of SCI.
It has been demonstrated that the blood pressure-raising effect of 3,4-threo-dihydroxyphenylserine (droxidopa) occurs independently of the central nervous system in human models of neurologic OH by conversion to norepinephrine (NE) in neuronal and non-neuronal tissue. Oral droxidopa is taken up by the more peripheral sympathetic neurons, converted to NE, stored and released appropriately during postural stress. Droxidopa has been used for the effective treatment of OH in several human models of neurologically caused autonomic disorders, such as familial amyloid polyneuropathy, autoimmune autonomic neuropathy, pure autonomic failure, and multiple system atrophy . The effectiveness of droxidopa at improving orthostatic blood pressure in persons with SCI has not been studied. To date, only a single case on the use of the drug in a person with SCI has been reported and the use droxidopa in that case was successful. The purpose of this proposal is to determine the dose effectiveness, duration of action and any adverse events following droxidopa administration in hypotensive individuals with SCI.
To determine the efficacy, duration of action and safety of escalating dose of droxidopa on systemic blood pressure, cerebral blood flow and vasoactive hormones and catecholamines during upright seated posture.
Primary Question:
- What is the lowest dose of droxidopa that increases seated SBP to 115±5 mmHg in men and 105±5 mmHg in women?
- When does the defined increase in SBP occur after oral ingestion of droxidopa?
- How long does this dose of droxidopa sustain SBP at these levels?
- What are the vital signs and the subjective symptomology following droxidopa administration?
Secondary Question:
- What is the MFV response to droxidopa administration in hypotensive individuals with SCI?
- Does an increase in SBP correspond to an increase in MCA MFV?
Tertiary Question:
- What is the vasoactive hormone and catecholamine response to droxidopa administration in hypotensive individuals with SCI?
- Does droxidopa administration result in a change in APR, Aldo or NE in hypotensive individuals with SCI?
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Droxidopa | Experimental | Drug: DroxidopaThe dose-titration response to ascending doses of Droxidopa (placebo, 100mg, 200mg, 400mg) will be measured four separate days. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- between the ages of 18 and 65,
- diagnosed with hypotension as defined above,
- able to provide informed consent
Key exclusion criteria (21 listed)
- Known or suspected sensitivity to study medication or any of its ingredients,
- current smoker,
- known coronary heart and/or artery disease,
- hypertension,
- diabetes mellitus or insipidus,
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 |
|---|---|---|
| DroxidopaAlso: L-DOPsDose titration of placebo, 100mg, 200mg, 400mg of Droxidopa will be given to assess the effects of Droxidopa on blood pressure and cerebral blood flow. | Drug | Droxidopa |
Primary outcome
The lowest dose of droxidopa that increases seated SBP to 115±5 mmHg in men and 105±5 mmHg in women
Time frame: 4 days
4 day titration of Droxidopa (placebo day 1, 100mg day 2, 200mg day 3, 400mg day). Blood pressure will be collected at the arm and finger (photoplethysmography) in 15 minute intervals during the duration of the protocol (approximately six hours). The subject will also wear a 24 hour portable arm blood pressure cuff, to assess the effect of Droxidopa on blood pressure 24 hrs post intervention.
2 secondary outcomes
The MFV response to droxidopa administration in hypotensive individuals with SCI
Time frame: 4 days
To assess the vasoactive hormone and catecholamine response to droxidopa administration in hypotensive individuals with SCI
Time frame: 4 days
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jul 2013.
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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.
Jill M Wecht, EdD principal investigator
James J. Peters VA 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 1 study testing Droxidopa in people with Spinal Cord Injury and Hypotension, run by Bronx VA 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 3 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 30 Jul 2013. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The lowest dose of droxidopa that increases seated SBP to 115±5 mmHg in men and 105±5 mmHg in women (time frame: 4 days). 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 30 Jul 2013.