A Dose Response Trial Using 5 and 10 Mg of Midodrine Hydrochloride
Status:
Completed
Trial end date:
2011-03-01
Target enrollment:
Participant gender:
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.