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Safety and Efficacy of L-NAME and Midodrine to Increase MAP
This study is not yet open for participant recruitment.
Verified by Department of Veterans Affairs, January 2009
First Received: January 30, 2009   No Changes Posted
Sponsored by: Department of Veterans Affairs
Information provided by: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00835224
  Purpose

After a spinal cord injury the brain is no longer completely in control of the body below the level of injury. This affects many organs and systems in the body, we are interested in understanding how a spinal cord injury affects blood pressure and blood flow to the brain. We are going to study blood pressure while the person is seated in a wheelchair before and after we give the subject medications which should increase blood pressure in a laboratory setting and over the course of a normal day in persons with spinal cord injury.


Condition Intervention Phase
Orthostatic Hypotension
Spinal Cord Injury
Drug: L-NAME
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, Randomized, Single Blind (Subject), Single Group Assignment, Safety/Efficacy Study
Official Title: Safety and Efficacy of L-NAME and Midodrine to Increase MAP in Persons With Tetraplegia

Further study details as provided by Department of Veterans Affairs:

Primary Outcome Measures:
  • Blood pressure [ Time Frame: Blood pressure during the 4 hour period after placebo (IV & oral), L-NAME (IV: 1.0 & 2.0 mg/kg) and midodrine (PO: 5.0 & 10.0 mg) administration ] [ Designated as safety issue: No ]

Estimated Enrollment: 105
Study Start Date: May 2009
Estimated Study Completion Date: March 2012
Estimated Primary Completion Date: March 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Blood pressure profile before and after administration of either Midodrine, L-NAME or placebo while the person is seated in a wheelchair and over the course of a normal day
Drug: L-NAME
Nitric Oxide inhibitor
Drug: Midodrine Hydrochloride
Alpha agonist and placebo

Detailed Description:

Blood pressure regulation is compromised in persons with tetraplegia due to de-centralization of sympathetic cardiovascular control, associated with hypotension during upright positioning (7, 10, 18, 33). An alpha receptor agonist (midodrine hydrochloride) has been reported to raise blood pressure in persons with tetraplegia (25, 26, 30). Midodrine is the only drug that is presently available to treat orthostatic hypotension. In the clinical armamentarium, it is always beneficial to have agents from multiple drug classes to treat a condition. In the treatment of hypertension, several classes of drugs may be prescribed to lower blood pressure, alone or in combination. The clinician and patient would benefit if another class of drug, with a totally separate mechanism of action, were available to treat orthostatic hypotension. A nitric oxide synthase inhibitor (NOSi), nitro-L-arginine methyl ester (L-NAME), has been shown by our group to "normalize" blood pressure in persons with tetraplegia (32). The safety and efficacy of these two hypertensive agents has not been investigated or compared in persons with chronic tetraplegia. Although the mechanism of action of each of these agents is appreciated, the relative cardiovascular effect in persons with SCI compared with controls is not known. The study will determine the efficacy and safety of these two medications at restoring mean arterial pressure (MAP) during daily activities in persons with chronic tetraplegia. Furthermore, the implication of restoring MAP to normal levels (80 10 mmHg) in individuals with tetraplegia on cardiovascular, autonomic, hormonal and cognitive function.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

Tetraplegia Subjects:

  1. chronic tetraplegia ( 1 year post injury) with a seated MAP of 65mmHg (almost all individuals with tetraplegia demonstrate this);
  2. Male or female with an age of 18 years or older (no upper limit);
  3. cervical SCI (C 3-8) & upper thoracic ( T 3)

Control Subjects:

1) Male or female with an age of 18 - 65 years

Exclusion Criteria:

Tetraplegia Subjects:

  1. acute illness;
  2. cardiovascular disease;
  3. renal disease;
  4. medications that affect the cardiovascular system.

Control Subjects:

  1. acute illness;
  2. cardiovascular disease;
  3. renal disease;
  4. medications that affect the cardiovascular system.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00835224

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

Locations
United States, New York
VA Medical Center, Bronx
Bronx, New York, United States, 10468
Sponsors and Collaborators
Investigators
Principal Investigator: Jill Wecht, EdD VA Medical Center, Bronx
  More Information

No publications provided

Responsible Party: Department of Veterans Affairs ( Wecht, Jill - Principal Investigator )
Study ID Numbers: A6161W, VA Project #5481-08-017
Study First Received: January 30, 2009
Last Updated: January 30, 2009
ClinicalTrials.gov Identifier: NCT00835224     History of Changes
Health Authority: United States: Federal Government;   United States: Food and Drug Administration

Study placed in the following topic categories:
Hypotension
Neurotransmitter Agents
Adrenergic alpha-Agonists
Hypotension, Orthostatic
Adrenergic Agents
Spinal Cord Diseases
Vascular Diseases
Wounds and Injuries
Central Nervous System Diseases
Disorders of Environmental Origin
Cardiovascular Agents
Quadriplegia
Trauma, Nervous System
Adrenergic Agonists
Nitric Oxide
Spinal Cord Injuries
NG-Nitroarginine Methyl Ester
Vasoconstrictor Agents
Midodrine
Postural Hypotension
Peripheral Nervous System Agents

Additional relevant MeSH terms:
Hypotension
Neurotransmitter Agents
Hypotension, Orthostatic
Spinal Cord Diseases
Adrenergic Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Disorders of Environmental Origin
Adrenergic Agonists
Spinal Cord Injuries
Therapeutic Uses
Midodrine
Vasoconstrictor Agents
Cardiovascular Diseases
Adrenergic alpha-Agonists
Sympathomimetics
Nervous System Diseases
Wounds and Injuries
Vascular Diseases
Central Nervous System Diseases
Trauma, Nervous System
Cardiovascular Agents
Pharmacologic Actions
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on May 07, 2009