Safety and Efficacy of L-NAME and Midodrine to Increase MAP

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Safety and Efficacy of L-NAME and Midodrine to Increase MAP in Persons With Tetraplegia

Conditions
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Orthostatic Hypotension, Spinal Cord Injury

Intervention / Treatment
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* Drug: L-NAME
* Drug: Midodrine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Spinal Cord Injured Subjects: chronic spinal cord injury (1 year post injury) with a seated MAP of 65mmHg (almost all individuals with tetraplegia demonstrate this) Male or female with an age of 18 - 65 years Control Subjects: Male or female with an age of 18 - 65 years Exclusion Criteria: Spinal Cord Injured Subjects: acute illness cardiovascular disease renal disease medications that affect the cardiovascular system Control Subjects: acute illness cardiovascular disease renal disease medications that affect the cardiovascular system

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Midodrine<br>A drug to treat low blood pressure. | Drug: Midodrine<br>* To treat low blood pressure.<br>|
| Experimental: L-Name<br>L-Name: A non-selective inhibitor of nitric oxide synthase and placebo. It has been used experimentally to induce hypertension. | Drug: L-NAME<br>* A non-selective inhibitor of nitric oxide synthase and placebo. It has been used experimentally to induce hypertension.<br>|
| Placebo Comparator: Placebo<br>Placebo: A pill with an inactive substance that looks like the study drug. | Drug: Placebo<br>* A pill with an inactive substance that looks like the study drug.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Blood Pressure |  | Blood pressure during the 4 hour period after no drug, L-NAME (IV: 1.0 mg/kg) and midodrine (PO: 10.0 mg) administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Spinal Cord Injury, Orthostatic Hypotension, Blood Pressure, Midodrine Hydrochloride, L-NAME