Safety and Efficacy of L-NAME and Midodrine to Increase MAP
After a spinal cord injury the brain is no longer completely in control of the body below the level of injury. This affects many organs and systems in the body, we are interested in understanding how a spinal cord injury affects blood pressure and blood flow to the brain. We are going to study blood pressure while the person is seated in a wheelchair before and after we give the subject medications which should increase blood pressure in a laboratory setting and over the course of a normal day in persons with spinal cord injury.
Spinal Cord Injury
Drug: Midodrine Hydrochloride
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Safety and Efficacy of L-NAME and Midodrine to Increase MAP in Persons With Tetraplegia|
- Blood pressure [ Time Frame: Blood pressure during the 4 hour period after no drug, L-NAME (IV: 1.0 mg/kg) and midodrine (PO: 10.0 mg) administration ] [ Designated as safety issue: No ]
|Study Start Date:||May 2010|
|Study Completion Date:||August 2013|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
Blood pressure profile before and after administration of either Midodrine, L-NAME or placebo while the person is seated in a wheelchair and over the course of a normal day
A non-selective inhibitor of nitric oxide synthase and placebo. It has been used experimentally to induce hypertension.Drug: Midodrine Hydrochloride
An adrenergic alpha agonist and placebo. It is used as a vasoconstrictor agent in the treatment of hypotension.
Blood pressure regulation is compromised in persons with tetraplegia due to de-centralization of sympathetic cardiovascular control, associated with hypotension during upright positioning (7, 10, 18, 33). An alpha receptor agonist (midodrine hydrochloride) has been reported to raise blood pressure in persons with tetraplegia (25, 26, 30). Midodrine is the only drug that is presently available to treat orthostatic hypotension. In the clinical armamentarium, it is always beneficial to have agents from multiple drug classes to treat a condition. In the treatment of hypertension, several classes of drugs may be prescribed to lower blood pressure, alone or in combination. The clinician and patient would benefit if another class of drug, with a totally separate mechanism of action, were available to treat orthostatic hypotension. A nitric oxide synthase inhibitor (NOSi), nitro-L-arginine methyl ester (L-NAME), has been shown by our group to "normalize" blood pressure in persons with tetraplegia (32). The safety and efficacy of these two hypertensive agents has not been investigated or compared in persons with chronic tetraplegia. Although the mechanism of action of each of these agents is appreciated, the relative cardiovascular effect in persons with SCI compared with controls is not known. The study will determine the efficacy and safety of these two medications at restoring mean arterial pressure (MAP) during daily activities in persons with chronic tetraplegia. Furthermore, the implication of restoring MAP to normal levels (80 10 mmHg) in individuals with tetraplegia on cardiovascular, autonomic, hormonal and cognitive function.
|United States, New York|
|VA Medical Center, Bronx|
|Bronx, New York, United States, 10468|
|Principal Investigator:||Jill Wecht, EdD||VA Medical Center, Bronx|