Clinical trial NCT00237770: Prevention of Low Blood Pressure in Persons With Tetraplegia
Official title: Prevention of Low Blood Pressure in Persons With Tetraplegia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Hypotension
Spinal Cord Injury
Keywords: Blood Pressure
Cardiovascular Autonomic Control
Nitric Oxide
NOS Inhibitor
Orthostatic Hypotension
Spinal Cord Injury
Tetraplegia
Lead sponsor: VA Office of Research and Development
Sponsor class: FED
First posted: 2005-10-12
Enrollment: 16
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief 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. 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.

Eligibility criteria: Inclusion Criteria:

* 18 to 65 year olds.
* Non-ambulatory Chronic tetraplegia (1 year after acute SCI).

Exclusion Criteria:

* 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;
* renal function abnormalities;
* diabetes mellitus;
* pituitary insufficiency;
* adrenal insufficiency;
* hypothyroidism; and
* medications known to affect the cardiovascular system.

Primary outcomes:
measure: Systolic Blood Pressure During Head-up Tilt
timeFrame: Average systolic blood pressure during head-up tilt (45 degrees) comparing active drug (L-NAME: 1.0 and 2.0 mg/kg) to placebo.
Secondary outcomes:
Other outcomes:
Locations:
city: Bronx
country: United States
facility: VA Medical Center, Bronx
state: New York
Study officials:
affiliation: VA Medical Center, Bronx
name: William Bauman, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
citation: 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.
citation: 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.