A Dose Response Trial Using 5 and 10 Mg of Midodrine Hydrochloride

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00426842
Recruitment Status : Completed
First Posted : January 25, 2007
Results First Posted : May 12, 2015
Last Update Posted : October 10, 2016
Information provided by (Responsible Party):
Jill M. Wecht, Ed.D., James J. Peters Veterans Affairs Medical Center

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.

Condition or disease Intervention/treatment Phase
Orthostatic Hypotension Spinal Cord Injury Drug: Midodrine Hydrochloride Phase 2

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.

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 11 participants
Intervention Model: Single Group Assignment
Masking: None (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
Study Start Date : January 2007
Actual Primary Completion Date : March 2011
Actual Study Completion Date : March 2011

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
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.

Primary Outcome Measures :
  1. 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)

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00426842

United States, New York
VA Medical Center, Bronx
Bronx, New York, United States, 10468
Sponsors and Collaborators
James J. Peters Veterans Affairs Medical Center
Principal Investigator: Jill Wecht, EdD VA Medical Center, Bronx
Principal Investigator: William Bauman, MD VA Medical Center, Bronx

Publications of Results:
Responsible Party: Jill M. Wecht, Ed.D., Research Health Scientist, James J. Peters Veterans Affairs Medical Center Identifier: NCT00426842     History of Changes
Other Study ID Numbers: 00893
VA Project #5481-06-051 ( Other Identifier: JJPVAMC IRB )
First Posted: January 25, 2007    Key Record Dates
Results First Posted: May 12, 2015
Last Update Posted: October 10, 2016
Last Verified: August 2016

Keywords provided by Jill M. Wecht, Ed.D., James J. Peters Veterans Affairs Medical Center:
Blood pressure
Orthostatic hypotension
Spinal Cord Injury
Sympathetic vascular control

Additional relevant MeSH terms:
Spinal Cord Injuries
Hypotension, Orthostatic
Spinal Cord Diseases
Central Nervous System Diseases
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Vascular Diseases
Cardiovascular Diseases
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Vasoconstrictor Agents
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action