A Dose Response Trial Using 5 and 10 Mg of Midodrine Hydrochloride
Primary Purpose
Orthostatic Hypotension, Spinal Cord Injury
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Midodrine Hydrochloride
Sponsored by
About this trial
This is an interventional treatment trial for Orthostatic Hypotension focused on measuring Blood pressure, Orthostatic hypotension, Spinal Cord Injury, Sympathetic vascular control, Midodrine
Eligibility 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
Sites / Locations
- VA Medical Center, Bronx
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Arm 1
Arm Description
Blood pressure response during HUT following administration of Midodrine Hydrochloride compared with no drug.
Outcomes
Primary Outcome Measures
Systolic Blood Pressure
brachial artery systolic blood pressure (mmHg)
Secondary Outcome Measures
Full Information
NCT ID
NCT00426842
First Posted
January 24, 2007
Last Updated
August 29, 2016
Sponsor
James J. Peters Veterans Affairs Medical Center
1. Study Identification
Unique Protocol Identification Number
NCT00426842
Brief Title
A Dose Response Trial Using 5 and 10 Mg of Midodrine Hydrochloride
Official Title
A Dose Response Trial Using 5 and 10 mg. of Midodrine Hydrochloride to Treat Orthostatic Hypotension in Persons With SCI
Study Type
Interventional
2. Study Status
Record Verification Date
August 2016
Overall Recruitment Status
Completed
Study Start Date
January 2007 (undefined)
Primary Completion Date
March 2011 (Actual)
Study Completion Date
March 2011 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
James J. Peters Veterans Affairs Medical Center
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief 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.
Detailed Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Orthostatic Hypotension, Spinal Cord Injury
Keywords
Blood pressure, Orthostatic hypotension, Spinal Cord Injury, Sympathetic vascular control, Midodrine
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Arm 1
Arm Type
Experimental
Arm Description
Blood pressure response during HUT following administration of Midodrine Hydrochloride compared with no drug.
Intervention Type
Drug
Intervention Name(s)
Midodrine Hydrochloride
Intervention Description
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.
Primary Outcome Measure Information:
Title
Systolic Blood Pressure
Description
brachial artery systolic blood pressure (mmHg)
Time Frame
The difference between the average supine systolic blood pressure and the average systolic blood pressure at 45 degree head-up tilt position.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jill Wecht, EdD
Organizational Affiliation
VA Medical Center, Bronx
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
William Bauman, MD
Organizational Affiliation
VA Medical Center, Bronx
Official's Role
Principal Investigator
Facility Information:
Facility Name
VA Medical Center, Bronx
City
Bronx
State/Province
New York
ZIP/Postal Code
10468
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
20801263
Citation
Wecht JM, Rosado-Rivera D, Handrakis JP, Radulovic M, Bauman WA. Effects of midodrine hydrochloride on blood pressure and cerebral blood flow during orthostasis in persons with chronic tetraplegia. Arch Phys Med Rehabil. 2010 Sep;91(9):1429-35. doi: 10.1016/j.apmr.2010.06.017.
Results Reference
result
PubMed Identifier
21762873
Citation
Wecht JM, Radulovic M, Rosado-Rivera D, Zhang RL, LaFountaine MF, Bauman WA. Orthostatic effects of midodrine versus L-NAME on cerebral blood flow and the renin-angiotensin-aldosterone system in tetraplegia. Arch Phys Med Rehabil. 2011 Nov;92(11):1789-95. doi: 10.1016/j.apmr.2011.03.022. Epub 2011 Jul 16.
Results Reference
result
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A Dose Response Trial Using 5 and 10 Mg of Midodrine Hydrochloride
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