A Dose Response Trial Using 5 and 10 Mg of Midodrine Hydrochloride
Condition: Orthostatic Hypotension; Spinal Cord Injury
MeSH terms: Spinal Cord Injuries; Hypotension, Orthostatic; Hypotension
Intervention: Midodrine Hydrochloride
Intervention description: Alpha1-agonist, exerts its actions via activation of the alpha-adrenergic receptors of the arteriolar and venous vasculature, producing an increase in vascular tone and elevation of blood pressure.
Intervention MeSH terms: Midodrine
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 11.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Blood pressure; Orthostatic hypotension; Spinal Cord Injury; Sympathetic vascular control; Midodrine

Summary:

      With upright postures, there is an immediate redistribution of blood to the dependent
      circulation; venous return and central venous filling pressure are reduced, resulting in
      diminution of cardiac output and blood pressure. These hemodynamic alterations stimulate the
      baroreceptor reflex, which is mediated via the central nervous system to increase peripheral
      sympathetic vasomotor tone, restoring blood pressure and cardiac output within
      seconds-to-minutes of the assumption of the upright position. Following SCI, individuals
      often experience the inability to adjust to postural changes due to disruption of central
      command of the baroreceptor reflex and reduction in efferent sympathetic neural pathways;
      consequently, orthostatic hypotension (OH) and symptoms of cerebral hypo-perfusion may ensue.
      OH is a well-documented phenomenon, which is characterized by a fall in systolic blood
      pressure of >20 mmHg or diastolic BP of > 10 mmHg within 3 minutes of assumption of an
      upright posture. As a consequence of OH, many individuals experience symptoms of cerebral
      hypo-perfusion which include lightheadedness, dizziness, blurry vision, fatigue, nausea,
      ringing in the ears, cognitive impairment and heart palpitations. Although several
      investigators have reported increased prevalence of OH during the acute phase of spinal cord
      injury (SCI), individuals with chronic injury also experience significant falls in blood
      pressure with seated upright postures. This investigation will examine the effects of an
      alpha-agonist, midodrine hydrochloride, during head-up tilt on systemic blood pressure,
      cerebral blood flow and cerebral oxygenation compared to placebo administration in persons
      with chronic SCI who demonstrate significant orthostatic hypotension during a 24-hour
      observation study. This is the first study to determine the dose response and efficacy of
      midodrine to improve orthostatic blood pressure and cerebral blood flow and oxygenation in
      the SCI population.
    

Eligibility criteria:

        Inclusion Criteria:

          -  This study will be performed on subjects 18 to 65 years old, with chronic SCI (> 1
             year), who are neurologically stable and have demonstrated significant hypotension
             (total time [proportion 50%] spent with hypotension [systolic BP below 110 mmHg for
             males and 100 mmHg for females] during a 24-hour observation.

        Exclusion Criteria:

          -  hypertension

          -  diabetes

          -  vascular disease

          -  cardiac disease

          -  cardiovascular medication

          -  pregnancy