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A Dose Response Trial Using 5 and 10 Mg of Midodrine Hydrochloride
This study is currently recruiting participants.
Verified by Department of Veterans Affairs, August 2008
Sponsored by: Department of Veterans Affairs
Information provided by: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00426842
  Purpose

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
Orthostatic Hypotension
Spinal Cord Injury
Drug: Midodrine Hydrochloride
Phase II

MedlinePlus related topics: Low Blood Pressure Spinal Cord Injuries
Drug Information available for: Midodrine Midodrine hydrochloride
U.S. FDA Resources
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

Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Blood pressure [ Time Frame: Blood pressure will be taken and recorded on both days (no drug and drug) every 15 minutes while supine and every 5 minutes during the 60-minute head-up tilt maneuver. ] [ Designated as safety issue: No ]

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
1: Experimental
Blood pressure response during HUT following Midodrine compared with placebo.
Drug: Midodrine Hydrochloride
Alpha agonist and placebo

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 orthostatic hypotension (total time [minutes] spent with hypotension [ 20% fall in mean arterial pressure from supine laboratory observation] during a 24-hour observation period.

Exclusion Criteria:

  • hypertension
  • diabetes
  • vascular disease
  • cardiac disease
  • cardiovascular medication
  • pregnancy
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00426842

Contacts
Contact: Jill Wecht, EdD jm.wecht@va.gov
Contact: Dwindally Rosado Rivera, EdD (718) 584-9000 ext 3128 dwindally.rosadorivera@va.gov

Locations
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            
Sponsors and Collaborators
Investigators
Principal Investigator: Jill Wecht, EdD VA Medical Center, Bronx
  More Information

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

Keywords provided by Department of Veterans Affairs:
Blood pressure
Orthostatic hypotension
Spinal Cord Injury
Sympathetic vascular control

Study placed in the following topic categories:
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

Additional relevant MeSH terms:
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

ClinicalTrials.gov processed this record on January 13, 2009