Safety and Efficacy of L-NAME and Midodrine to Increase MAP

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00835224
First received: January 30, 2009
Last updated: September 9, 2013
Last verified: September 2013

January 30, 2009
September 9, 2013
May 2010
June 2013   (final data collection date for primary outcome measure)
Blood pressure [ Time Frame: Blood pressure during the 4 hour period after no drug, L-NAME (IV: 1.0 mg/kg) and midodrine (PO: 10.0 mg) administration ] [ Designated as safety issue: No ]
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 ]
Complete list of historical versions of study NCT00835224 on ClinicalTrials.gov Archive Site
Not Provided
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Safety and Efficacy of L-NAME and Midodrine to Increase MAP
Safety and Efficacy of L-NAME and Midodrine to Increase MAP in Persons With Tetraplegia

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.

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.

Interventional
Phase 2
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Orthostatic Hypotension
  • Spinal Cord Injury
  • Drug: L-NAME
    A non-selective inhibitor of nitric oxide synthase and placebo. It has been used experimentally to induce hypertension.
  • Drug: Midodrine Hydrochloride
    An adrenergic alpha agonist and placebo. It is used as a vasoconstrictor agent in the treatment of hypotension.
Experimental: Arm 1
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
Interventions:
  • Drug: L-NAME
  • Drug: Midodrine Hydrochloride
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
August 2013
June 2013   (final data collection date for primary outcome measure)

Inclusion Criteria:

Spinal Cord Injured Subjects:

  • chronic spinal cord injury (1 year post injury) with a seated MAP of 65mmHg (almost all individuals with tetraplegia demonstrate this)
  • Male or female with an age of 18 - 65 years

Control Subjects:

  • Male or female with an age of 18 - 65 years

Exclusion Criteria:

Spinal Cord Injured Subjects:

  • acute illness
  • cardiovascular disease
  • renal disease
  • medications that affect the cardiovascular system

Control Subjects:

  • acute illness
  • cardiovascular disease
  • renal disease
  • medications that affect the cardiovascular system
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00835224
A6161-W, VA Project #5481-08-017
No
Department of Veterans Affairs
Department of Veterans Affairs
Not Provided
Principal Investigator: Jill Wecht, EdD VA Medical Center, Bronx
Department of Veterans Affairs
September 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP