Prevention of Low Blood Pressure in Persons With Tetraplegia

US Department of Veterans Affairs (VA)

Status and phase: Completed; Phase 3; Phase 2

Conditions: Hypotension; Spinal Cord Injury

Treatments: Procedure: Head-up Tilt maneuver; Drug: N-Nitro L-arginine-methylester (L-NAME)

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT00237770

B3600-R

Details and patient eligibility

About

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.

Full 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.

Enrollment: 16 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Crossover Assignment

Masking: None (Open label)

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16 participants in 1 patient group, including a placebo group

Arm 1

Placebo Comparator group

Description:

Placebo control (normal saline) is employed on a separate visit during procedure.

Treatment:

Procedure: Head-up Tilt maneuver

Drug: N-Nitro L-arginine-methylester (L-NAME)