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

US Department of Veterans Affairs (VA)

Status and phase: Completed; Phase 2

Conditions: Spinal Cord Injury; Orthostatic Hypotension

Treatments: Drug: L-NAME; Drug: Placebo; Drug: Midodrine

Study type: Interventional

Funder types: Other U.S. Federal agency

Identifiers

NCT00835224

VA Project #5481-08-017 (Other Identifier)

A6161-W

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 34 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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34 participants in 3 patient groups, including a placebo group

Midodrine

Experimental group

Description:

A drug to treat low blood pressure.

Treatment:

Drug: Midodrine

L-Name

Experimental group

Description:

L-Name: A non-selective inhibitor of nitric oxide synthase and placebo. It has been used experimentally to induce hypertension.

Treatment:

Drug: L-NAME

Placebo

Placebo Comparator group

Description:

Placebo: A pill with an inactive substance that looks like the study drug.

Treatment:

Drug: Placebo