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: March 21, 2014
Last verified: March 2014
  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
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Safety and Efficacy of L-NAME and Midodrine to Increase MAP in Persons With Tetraplegia

Resource links provided by NLM:


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 no drug, L-NAME (IV: 1.0 mg/kg) and midodrine (PO: 10.0 mg) administration ] [ Designated as safety issue: No ]

Enrollment: 34
Study Start Date: May 2010
Study Completion Date: August 2013
Primary Completion Date: June 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Midodrine
A drug to treat low blood pressure.
Drug: Midodrine
To treat low blood pressure.
Experimental: L-Name
L-Name: A non-selective inhibitor of nitric oxide synthase and placebo. It has been used experimentally to induce hypertension.
Drug: L-NAME
A non-selective inhibitor of nitric oxide synthase and placebo. It has been used experimentally to induce hypertension.
Placebo Comparator: Placebo
Placebo: A pill with an inactive substance that looks like the study drug.
Drug: Placebo
A pill with an inactive substance that looks like the study drug.

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:

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00835224

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

Publications:
Responsible Party: Department of Veterans Affairs
ClinicalTrials.gov Identifier: NCT00835224     History of Changes
Other Study ID Numbers: A6161-W, VA Project #5481-08-017
Study First Received: January 30, 2009
Results First Received: September 12, 2013
Last Updated: March 21, 2014
Health Authority: United States: Federal Government
United States: Food and Drug Administration

Keywords provided by Department of Veterans Affairs:
Spinal Cord Injury
Orthostatic Hypotension
Blood Pressure
Midodrine Hydrochloride
L-NAME

Additional relevant MeSH terms:
Hypotension
Hypotension, Orthostatic
Spinal Cord Injuries
Wounds and Injuries
Vascular Diseases
Cardiovascular Diseases
Orthostatic Intolerance
Primary Dysautonomias
Autonomic Nervous System Diseases
Nervous System Diseases
Spinal Cord Diseases
Central Nervous System Diseases
Trauma, Nervous System
Midodrine
NG-Nitroarginine Methyl Ester
Sympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Vasoconstrictor Agents
Cardiovascular Agents
Therapeutic Uses
Adrenergic alpha-1 Receptor Agonists
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors

ClinicalTrials.gov processed this record on July 20, 2014