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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.
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Arm 1 | Placebo Comparator | Placebo control (normal saline) is employed on a separate visit during procedure. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| N-Nitro L-arginine-methylester (L-NAME) | Drug | A non-specific inhibitor of the nitric oxide synthase enzyme. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Systolic Blood Pressure During Head-up Tilt | Average systolic blood pressure over 45 minutes at 45 degrees of head-up tilt. | Average systolic blood pressure during head-up tilt (45 degrees) comparing active drug (L-NAME: 1.0 and 2.0 mg/kg) to placebo. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| William Bauman, MD | VA Medical Center, Bronx | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| VA Medical Center, Bronx | The Bronx | New York | 10468 | United States |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 17385265 | Result | 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. | |
| 17965289 | Result | Wecht 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. |
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No subject was excluded after enrollment prior to participation.
Recruitment occured from January 2006 through May 2009; participants were recruited from the James J Peters VA Medical Center and the surrounding community.
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| ID | Title | Description |
|---|---|---|
| FG000 | Tetraplegic Subjects | All tetraplegic subjects underwent a head-up tilt maneuver to determine systolic blood pressure responses to placebo L-NAME 1.0 mg/kg and L-NAME 2.0 mg/kg. Subjects with tetraplegia visited the laboratory on 3 separate occasions. |
| FG001 | Control Subjects | Systolic blood pressure responses to head-up tilt were determined in non-spinal cord injured control subjects following placebo administration. Control subjects visited the laboratory for 1 visit. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Individuals With Tetraplegia | Systolic blood pressure responses to head-up tilt were determined after placebo, L-NAME (1.0 mg/kg) and L-NAME administration (2.0 mg/kg) administration. |
| BG001 | Able-bodied Controls |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Systolic Blood Pressure During Head-up Tilt | Average systolic blood pressure over 45 minutes at 45 degrees of head-up tilt. | Posted | Mean | Standard Deviation | mmHg | Average systolic blood pressure during head-up tilt (45 degrees) comparing active drug (L-NAME: 1.0 and 2.0 mg/kg) to placebo. |
|
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Tetraplegic Systolic Blood Pressure Responses to Placebo | Systolic blood pressure responses to head-up tilt were determined after placebo administration in persons with tetraplegia |
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The small sample of subjects tested and the heterogeneity of spinal lesions.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jill M. Wecht, principal Investigator | James J Peters VA Medical Center | 718 584-9000 | 3122 | jm.wecht@va.gov |
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| ID | Term |
|---|---|
| D007022 | Hypotension |
| D013119 | Spinal Cord Injuries |
| D007024 | Hypotension, Orthostatic |
| D011782 | Quadriplegia |
| ID | Term |
|---|---|
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D013118 | Spinal Cord Diseases |
| D002493 | Central Nervous System Diseases |
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| ID | Term |
|---|---|
| D019331 | NG-Nitroarginine Methyl Ester |
| ID | Term |
|---|---|
| D001120 | Arginine |
| D024361 | Amino Acids, Basic |
| D000596 | Amino Acids |
| D000602 | Amino Acids, Peptides, and Proteins |
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| Head-up Tilt maneuver | Procedure | 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. |
|
| 19651280 | Result | Wecht 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. |
| 21762873 | Result | Wecht 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. |
| 23700789 | Derived | La 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. |
Systolic blood pressure responses to head-up tilt were determined in able-bodied controls following placebo administration
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Age, Continuous | Mean | Standard Deviation | years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG002 | Tetraplegic Systolic Blood Pressure Responses to L-NAME 1.0 mg | Systolic blood pressure responses to head-up tilt were determined following administration of L-NAME (1.0 mg/kg) |
| OG003 | Tetraplegic Systolic Blood Pressure Responses to L-NAME 2.0 mg | Systolic blood pressure responses during head-up tilt were determined following L-NAME administration (2.0 mg/kg) |
|
|
| 0 |
| 9 |
| 0 |
| 9 |
| EG001 | Control Systolic Blood Pressure Responses to Placebo | Systolic blood pressure responses to head-up tilt were determined in non spinal cord injured controls following placebo administration | 0 | 7 | 0 | 7 |
| EG002 | Tetraplegic Systolic Blood Pressure Responses to L-NAME 1.0 mg | Systolic blood pressure responses to head-up tilt were determined following administration of L-NAME (1.0 mg/kg) | 0 | 9 | 0 | 9 |
| EG003 | Tetraplegic Systolic Blood Pressure Responses to L-NAME 2.0 mg | Systolic blood pressure responses during head-up tilt were determined following L-NAME administration (2.0 mg/kg) | 0 | 9 | 0 | 9 |
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| D009422 | Nervous System Diseases |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
| D054971 | Orthostatic Intolerance |
| D054969 | Primary Dysautonomias |
| D001342 | Autonomic Nervous System Diseases |
| D010243 | Paralysis |
| D009461 | Neurologic Manifestations |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D000599 |
| Amino Acids, Diamino |