A Dose Response Trial Using 5 and 10 Mg of Midodrine Hydrochloride
|Orthostatic Hypotension Spinal Cord Injury||Drug: Midodrine Hydrochloride||Phase 2|
|Study Design:||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Dose Response Trial Using 5 and 10 mg. of Midodrine Hydrochloride to Treat Orthostatic Hypotension in Persons With SCI|
- Systolic Blood Pressure [ Time Frame: The difference between the average supine systolic blood pressure and the average systolic blood pressure at 45 degree head-up tilt position. ]brachial artery systolic blood pressure (mmHg)
|Study Start Date:||January 2007|
|Study Completion Date:||March 2011|
|Primary Completion Date:||March 2011 (Final data collection date for primary outcome measure)|
Experimental: Arm 1
Blood pressure response during HUT following administration of Midodrine Hydrochloride compared with no drug.
Drug: Midodrine Hydrochloride
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00426842
|United States, New York|
|VA Medical Center, Bronx|
|Bronx, New York, United States, 10468|
|Principal Investigator:||Jill Wecht, EdD||VA Medical Center, Bronx|
|Principal Investigator:||William Bauman, MD||VA Medical Center, Bronx|