| City: |
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Bronx |
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State:
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NY |
| Zip Code: |
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10468 |
| Conditions: |
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Orthostatic Hypotension - Spinal Cord Injury |
| Purpose: |
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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.
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| Study summary: |
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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. |
| Criteria: |
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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 |
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If you are interested in this clinical trial please use the contact information above. If you would like to get additional information about this clinical trial please visit ClinicalTrials.gov.
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| Data Source: |
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ClinicalTrials.gov |
| Date Processed: |
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December 29, 2009 |
Modifications to
this listing: |
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Only selected fields are shown, please use the link
above to view all information about this clinical trial. |
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