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Sponsored by: |
Department of Veterans Affairs |
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Information provided by: | Department of Veterans Affairs |
ClinicalTrials.gov Identifier: | NCT00426842 |
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.
Condition | Intervention | Phase |
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Orthostatic Hypotension Spinal Cord Injury |
Drug: Midodrine Hydrochloride |
Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Non-Randomized, Open Label, Dose Comparison, Single Group Assignment, Efficacy Study |
Official Title: | A Dose Response Trial Using 5 and 10 mg. of Midodrine Hydrochloride to Treat Orthostatic Hypotension in Persons With SCI |
Estimated Enrollment: | 16 |
Study Start Date: | January 2007 |
Estimated Study Completion Date: | March 2011 |
Estimated Primary Completion Date: | March 2011 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
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1: Experimental
Blood pressure response during HUT following Midodrine compared with placebo.
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Drug: Midodrine Hydrochloride
Alpha agonist and placebo
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In individuals with SCI, blood pressure regulation is altered compared to the non-SCI population and relates to the degree of sympathetic vascular denervation. The inadequate release of norepinephrine with postural change is a primary component of OH and several reports have documented significantly reduced plasma norepinephrine levels in individuals with tetraplegia. Ephedrine sulfate and midodrine hydrochloride, both 1 receptor agonists, are recommended for the treatment of postural hypotension in this population. Although there are case reports documenting improved blood pressure regulation in persons with SCI treated with an 1 receptor agonist, this pharmacological treatment for OH has not been adequately studied in this population. A dose response trial will be used to determine the efficacy of midodrine hydrochloride (5 and 10 mg) compared to no drug at improving systemic blood pressure, cerebral blood flow and oxygenation and at reducing symptomatic hypotension during tilt-table testing in 16 individuals with SCI who manifest significant orthostatic hypotension (total time [minutes] spent with hypotension [ 20% fall in mean arterial pressure from supine laboratory observation] over a 24-hour observation.
Subjects will receive, in an increasing dose manner and on separate days: no drug, 5 and 10 mg of oral midodrine hydrochloride. Oral ingestion of the pill (placebo or midodrine) will be at 30 minutes during the 60 minute supine rest period prior to the head-up tilt maneuver.
A progressive head-up tilt will be utilized in which the table will be adjusted to 15 , 25 , 35 for 5 minutes at each angle and then will be maintained at 45 for 45 minutes or until the subjects experiences symptoms of compromised cerebral blood flow, which include, but are not limited to, light headedness, blurry vision, dizziness and nausea. Throughout each test day, measurements of heart rate, blood pressure, middle cerebral blood flow velocity, and cerebral oxygenation will be obtained. In addition, blood draws will be completed to capture humoral factors responsible for blood pressure regulation.
Ages Eligible for Study: | 18 Years to 65 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
Contact: Jill Wecht, EdD | jm.wecht@va.gov | |
Contact: Dwindally Rosado Rivera, EdD | (718) 584-9000 ext 3128 | dwindally.rosadorivera@va.gov |
United States, New York | |
VA Medical Center, Bronx | Recruiting |
Bronx, New York, United States, 10468 | |
Contact: Jill Wecht, EdD jm.wecht@va.gov | |
Sub-Investigator: William Bauman, MD | |
Principal Investigator: Jill Wecht, EdD |
Principal Investigator: | Jill Wecht, EdD | VA Medical Center, Bronx |
Responsible Party: | Department of Veterans Affairs ( Wecht, Jill - Principal Investigator ) |
Study ID Numbers: | 00893, VA Project # #5481-06-051 |
Study First Received: | January 24, 2007 |
Last Updated: | August 14, 2008 |
ClinicalTrials.gov Identifier: | NCT00426842 |
Health Authority: | United States: Federal Government; United States: Food and Drug Administration |
Blood pressure Orthostatic hypotension Spinal Cord Injury Sympathetic vascular control |
Hypotension Spinal Cord Injuries Postural hypotension Hypotension, Orthostatic Spinal Cord Diseases Midodrine |
Wounds and Injuries Vascular Diseases Disorders of Environmental Origin Central Nervous System Diseases Trauma, Nervous System |
Neurotransmitter Agents Adrenergic alpha-Agonists Adrenergic Agents Molecular Mechanisms of Pharmacological Action Sympathomimetics Nervous System Diseases Physiological Effects of Drugs Cardiovascular Agents |
Adrenergic Agonists Pharmacologic Actions Autonomic Agents Therapeutic Uses Vasoconstrictor Agents Cardiovascular Diseases Peripheral Nervous System Agents |