A Dose Response Trial Using 5 and 10 Mg of Midodrine Hydrochloride

• Status: Completed
• Trial end date: 2011-03-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: James J. Peters Veterans Affairs Medical Center
• Treatments: Midodrine

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