Safety and Efficacy of L-NAME and Midodrine to Increase MAP
Condition: Orthostatic Hypotension; Spinal Cord Injury
MeSH terms: Spinal Cord Injuries; Hypotension, Orthostatic; Hypotension
Study type: Interventional
Phase: Phase 2

Summary: 
      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: 
      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.
    

Intervention name(s): L-NAME; Midodrine; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): A non-selective inhibitor of nitric oxide synthase and placebo. It has been used experimentally to induce hypertension.; To treat low blood pressure.; A pill with an inactive substance that looks like the study drug.
Intervention MeSH terms: Midodrine
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Spinal Cord Injury; Orthostatic Hypotension; Blood Pressure; Midodrine Hydrochloride; L-NAME