HypotensionPhase 2/3NCT00237770
Prevention of Low Blood Pressure in Persons With Tetraplegia
A Phase 2/3 study testing N-Nitro L-arginine-methylester (L-NAME) and Head-up Tilt maneuver in people with Hypotension and Spinal Cord Injury, run by US Department of Veterans Affairs at 1 site in United States.
Trial summary
The aim of this investigation is to determine the blood pressure response to NOS inhibition, with L-NAME, in persons with tetraplegia compared to non-SCI control subjects and to establish if blood pressure can be increased while upright in those with tetraplegia. Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Hypotension, Spinal Cord Injury
- What is being tested?
- N-Nitro L-arginine-methylester (L-NAME) and Head-up Tilt maneuver
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Jun 2003to Jun 2010
- Phase
- Phase 2/3
- 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 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 18 to 65 year olds.
- Non-ambulatory Chronic tetraplegia (1 year after acute SCI).
Who cannot join
- central nervous system disease (other than SCI) e.g., multiple sclerosis, amyotrophic lateral sclerosis, syringomyelia, tabes dorsalis;
- peripheral neuropathies;
- surgical sympathectomy;
- coronary heart and/or artery disease;
- anemia;
- hypertension;
Show all 12Show fewer
- renal function abnormalities;
- diabetes mellitus;
- pituitary insufficiency;
- adrenal insufficiency;
- hypothyroidism; and
- medications known to affect the cardiovascular system.
Trial locations and contacts
1 site in 1 country.
About this study
The aim of this investigation is to determine the blood pressure response to NOS inhibition, with L-NAME, in persons with tetraplegia compared to non-SCI control subjects and to establish if blood pressure can be increased while upright in those with tetraplegia. If blood pressure is increased with NOS inhibition in persons with tetraplegia, this would improve our treatment of the condition of low blood pressure during seated postures in individuals with tetraplegia.
Read the detailed description
Despite disruption of central command of the vasculature during orthostatic maneuvers, individuals with tetraplegia are generally able to be seated in an upright position for long periods of time without developing symptoms of orthostatic intolerance. It must be appreciated however, that orthostatic hypotension may occur unpredictably in persons with chronic tetraplegia. This may result in a range of symptoms due to cerebral hypoperfusion from mild reduction in mental acuity to loss of consciousness. Nitric oxide (NO) is the most potent endogenous vasodilator which is synthesized by the enzyme NO synthase (NOS) and may be largely responsible for orthostatic hypotension in individuals with immobilizing conditions. Recent evidence suggests an up-regulation of inducible nitric oxide synthases (NOS) activity with prolonged exposure to hind limb suspension. The effects of NOS inhibition during orthostasis on blood pressure regulation in those with chronic tetraplegia may provide insight into effective pharmacological therapy to reduce or prevent pathologic orthostatic changes. Treatment with a NOS inhibitor may facilitate the process of mobilization in those with acute higher cord lesions.
- Conditions
- Hypotension, Spinal Cord Injury
- Being tested
- N-Nitro L-arginine-methylester (L-NAME), Head-up Tilt maneuver
- Keywords
- Blood Pressure, Cardiovascular Autonomic Control, Nitric Oxide, NOS Inhibitor, Orthostatic Hypotension, Spinal Cord Injury, Tetraplegia
- Medical subject headings
- Hypotension, Spinal Cord Injuries, Hypotension, Orthostatic, Quadriplegia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-Nitro L-arginine-methylester (L-NAME)Drug
A non-specific inhibitor of the nitric oxide synthase enzyme.
Head-up Tilt maneuverProcedure or surgery
Participant will be placed onto tilt table and brought to 15 degrees of head up tilt for 60 minutes (intravenous infusion time). After this time, a progressive increase to 45 degrees will be completed with a 10 degree increase every 5 minutes. Participant will remain at 45 degrees for 45 minutes or until symptom onset.
| Study group | Role | What they receive |
|---|---|---|
| Arm 1 | Placebo comparator | Placebo control (normal saline) is employed on a separate visit during procedure. Receives: Drug: N-Nitro L-arginine-methylester (L-NAME); Procedure: Head-up Tilt maneuver |
What is being measured
The primary outcome is the main question the study is designed to answer.
Systolic Blood Pressure During Head-up Tilt
Average systolic blood pressure over 45 minutes at 45 degrees of head-up tilt.
Measured: Average systolic blood pressure during head-up tilt (45 degrees) comparing active drug (L-NAME: 1.0 and 2.0 mg/kg) to placebo.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Oct 2005 (estimated)
- Study startJun 2003
- Primary completionJun 2010
- Study completionJun 2010
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.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for HypotensionStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Lead sponsor
- US Department of Veterans Affairs
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- William Bauman, MD, Principal investigator, VA Medical Center, Bronx
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00237770
- Sponsor's protocol ID
- B3600-R
- Status last verified
- Apr 2014
- First submitted
- 7 Oct 2005
- Last updated
- 19 May 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Wecht JM, Weir JP, Krothe AH, Spungen AM, Bauman WA. Normalization of supine blood pressure after nitric oxide synthase inhibition in persons with tetraplegia. J Spinal Cord Med. 2007;30(1):5-9. doi: 10.1080/10790268.2007.11753907.
PubMed 17385265Wecht JM, Weir JP, Goldstein DS, Krothe-Petroff A, Spungen AM, Holmes C, Bauman WA. Direct and reflexive effects of nitric oxide synthase inhibition on blood pressure. Am J Physiol Heart Circ Physiol. 2008 Jan;294(1):H190-7. doi: 10.1152/ajpheart.00366.2007. Epub 2007 Oct 26.
PubMed 17965289Wecht JM, Radulovic M, Lafountaine MF, Rosado-Rivera D, Zhang RL, Bauman WA. Orthostatic responses to nitric oxide synthase inhibition in persons with tetraplegia. Arch Phys Med Rehabil. 2009 Aug;90(8):1428-34. doi: 10.1016/j.apmr.2009.02.004.
PubMed 19651280Wecht JM, Radulovic M, Rosado-Rivera D, Zhang RL, LaFountaine MF, Bauman WA. Orthostatic effects of midodrine versus L-NAME on cerebral blood flow and the renin-angiotensin-aldosterone system in tetraplegia. Arch Phys Med Rehabil. 2011 Nov;92(11):1789-95. doi: 10.1016/j.apmr.2011.03.022. Epub 2011 Jul 16.
PubMed 21762873La Fountaine MF, Wecht JM, Bauman WA. Acute nitric oxide synthase inhibition and cardiac conduction in persons with spinal cord injury: a short report. Pharmazie. 2013 Apr;68(4):245-50.
PubMed 23700789
Study at a glance
From the registry record, last updated by the sponsor on 19 May 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Prevention of Low Blood Pressure in Persons With Tetraplegia
- ClinicalTrials.gov ID
- NCT00237770
- Acronym / sponsor ID
- B3600-R
- Conditions
- Hypotension, Spinal Cord Injury
- Keywords
- Blood Pressure, Cardiovascular Autonomic Control, Nitric Oxide, NOS Inhibitor, Orthostatic Hypotension, Spinal Cord Injury, Tetraplegia
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- US Department of Veterans AffairsUS federal agency
- Study start
- Jun 2003
- Primary completion
- Jun 2010 (actual)
- Study completion
- Jun 2010 (actual)
- First posted
- 12 Oct 2005 (estimated)
- Results
- Posted 19 May 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The aim of this investigation is to determine the blood pressure response to NOS inhibition, with L-NAME, in persons with tetraplegia compared to non-SCI control subjects and to establish if blood pressure can be increased while upright in those with tetraplegia. If blood pressure is increased with NOS inhibition in persons with tetraplegia, this would improve our treatment of the condition of low blood pressure during seated postures in individuals with tetraplegia.
Detailed description
Despite disruption of central command of the vasculature during orthostatic maneuvers, individuals with tetraplegia are generally able to be seated in an upright position for long periods of time without developing symptoms of orthostatic intolerance. It must be appreciated however, that orthostatic hypotension may occur unpredictably in persons with chronic tetraplegia. This may result in a range of symptoms due to cerebral hypoperfusion from mild reduction in mental acuity to loss of consciousness. Nitric oxide (NO) is the most potent endogenous vasodilator which is synthesized by the enzyme NO synthase (NOS) and may be largely responsible for orthostatic hypotension in individuals with immobilizing conditions. Recent evidence suggests an up-regulation of inducible nitric oxide synthases (NOS) activity with prolonged exposure to hind limb suspension. The effects of NOS inhibition during orthostasis on blood pressure regulation in those with chronic tetraplegia may provide insight into effective pharmacological therapy to reduce or prevent pathologic orthostatic changes. Treatment with a NOS inhibitor may facilitate the process of mobilization in those with acute higher cord lesions.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm 1 | Placebo comparator | Drug: N-Nitro L-arginine-methylester (L-NAME), Procedure: Head-up Tilt maneuverPlacebo control (normal saline) is employed on a separate visit during procedure. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 18 to 65 year olds.
- Non-ambulatory Chronic tetraplegia (1 year after acute SCI).
Key exclusion criteria (12 listed)
- central nervous system disease (other than SCI) e.g., multiple sclerosis, amyotrophic lateral sclerosis, syringomyelia, tabes dorsalis;
- peripheral neuropathies;
- surgical sympathectomy;
- coronary heart and/or artery disease;
- anemia;
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 |
|---|---|---|
| N-Nitro L-arginine-methylester (L-NAME)A non-specific inhibitor of the nitric oxide synthase enzyme. | Drug | Arm 1 |
| Head-up Tilt maneuverParticipant will be placed onto tilt table and brought to 15 degrees of head up tilt for 60 minutes (intravenous infusion time). After this time, a progressive increase to 45 degrees will be completed with a 10 degree increase every 5 minutes. Participant will remain at 45 degrees for 45 minutes or until symptom onset. | Procedure or surgery | Arm 1 |
Primary outcome
Systolic Blood Pressure During Head-up Tilt
Time frame: Average systolic blood pressure during head-up tilt (45 degrees) comparing active drug (L-NAME: 1.0 and 2.0 mg/kg) to placebo.
Average systolic blood pressure over 45 minutes at 45 degrees of head-up tilt.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 May 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 17385265Wecht JM, Weir JP, Krothe AH, Spungen AM, Bauman WA. Normalization of supine blood pressure after nitric oxide synthase inhibition in persons with tetraplegia. J Spinal Cord Med. 2007;30(1):5-9. doi: 10.1080/10790268.2007.11753907.
- Results publication: PubMed 17965289Wecht JM, Weir JP, Goldstein DS, Krothe-Petroff A, Spungen AM, Holmes C, Bauman WA. Direct and reflexive effects of nitric oxide synthase inhibition on blood pressure. Am J Physiol Heart Circ Physiol. 2008 Jan;294(1):H190-7. doi: 10.1152/ajpheart.00366.2007. Epub 2007 Oct 26.
- Results publication: PubMed 19651280Wecht JM, Radulovic M, Lafountaine MF, Rosado-Rivera D, Zhang RL, Bauman WA. Orthostatic responses to nitric oxide synthase inhibition in persons with tetraplegia. Arch Phys Med Rehabil. 2009 Aug;90(8):1428-34. doi: 10.1016/j.apmr.2009.02.004.
- Results publication: PubMed 21762873Wecht JM, Radulovic M, Rosado-Rivera D, Zhang RL, LaFountaine MF, Bauman WA. Orthostatic effects of midodrine versus L-NAME on cerebral blood flow and the renin-angiotensin-aldosterone system in tetraplegia. Arch Phys Med Rehabil. 2011 Nov;92(11):1789-95. doi: 10.1016/j.apmr.2011.03.022. Epub 2011 Jul 16.
- Derived from this study: PubMed 23700789La Fountaine MF, Wecht JM, Bauman WA. Acute nitric oxide synthase inhibition and cardiac conduction in persons with spinal cord injury: a short report. Pharmazie. 2013 Apr;68(4):245-50.
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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.
William Bauman, MD principal investigator
VA Medical Center, Bronx
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing N-Nitro L-arginine-methylester (L-NAME) and Head-up Tilt maneuver in people with Hypotension and Spinal Cord Injury, run by US Department of Veterans Affairs 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 2 inclusion and 12 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 19 May 2014. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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 19 May 2014). 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?
Systolic Blood Pressure During Head-up Tilt (time frame: Average systolic blood pressure during head-up tilt (45 degrees) comparing active drug (L-NAME: 1.0 and 2.0 mg/kg) to placebo.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00237770, which also lists 5 linked publications.
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 19 May 2014.