Prevention of Low Blood Pressure in Persons With Tetraplegia

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Department of Veterans Affairs
ClinicalTrials.gov Identifier:
NCT00237770
First received: October 7, 2005
Last updated: April 23, 2014
Last verified: April 2014

October 7, 2005
April 23, 2014
June 2003
June 2010   (final data collection date for primary outcome measure)
Systolic Blood Pressure During Head-up Tilt [ Time Frame: Average systolic blood pressure during head-up tilt (45 degrees) comparing active drug (L-NAME: 1.0 and 2.0 mg/kg) to placebo. ] [ Designated as safety issue: No ]
Average systolic blood pressure over 45 minutes at 45 degrees of head-up tilt.
  • To determine the supine (study 1a) and orthostatic
  • (study 1b) blood pressure response to NOS inhibition with
  • L-NAME in persons with chronic complete tetraplegia compared to non-SCI control subjects.
Complete list of historical versions of study NCT00237770 on ClinicalTrials.gov Archive Site
Not Provided
  • The secondary objectives are:
  • In persons with chronic tetraplegia compared to non-SCI controls:
  • 1. To determine the minimum dose of L-NAME that results in the maximum blood pressure response without exceeding normotensive values, i.e. ≤ 180 systolic or ≤ 110 diastolic mmHg at the end of drug infusion (60 minutes).
  • 2. To determine the absolute and relative (percent of baseline) peak MAP response to L-NAME.
  • 3. To determine the time to peak MAP following L-NAME administration.
  • 4. To determine the duration of action (i.e., the length of time at which blood pressure remains elevated ≥5% of baseline) for L-NAME.
  • 5. To determine the sympathetic response (i.e., plasma NE and heart rate/blood pressure variabilities) to L-NAME.
  • 6. To determine change in airway resistance as measured by the impulse oscillation system (IOS) following infusion of L-NAME.
  • 7. Determine the role of L-NAME on platelet aggregation.
Not Provided
Not Provided
 
Prevention of Low Blood Pressure in Persons With Tetraplegia
Prevention of Low Blood Pressure in Persons With Tetraplegia

The aim of this investigation is to determine the blood pressure response to NOS inhibition, with L-NAME, in persons with tetraplegia compared to non-SCI control subjects and to establish if blood pressure can be increased while upright in those with tetraplegia. If blood pressure is increased with NOS inhibition in persons with tetraplegia, this would improve our treatment of the condition of low blood pressure during seated postures in individuals with tetraplegia.

Despite disruption of central command of the vasculature during orthostatic maneuvers, individuals with tetraplegia are generally able to be seated in an upright position for long periods of time without developing symptoms of orthostatic intolerance. It must be appreciated however, that orthostatic hypotension may occur unpredictably in persons with chronic tetraplegia. This may result in a range of symptoms due to cerebral hypoperfusion from mild reduction in mental acuity to loss of consciousness. Nitric oxide (NO) is the most potent endogenous vasodilator which is synthesized by the enzyme NO synthase (NOS) and may be largely responsible for orthostatic hypotension in individuals with immobilizing conditions. Recent evidence suggests an up-regulation of inducible nitric oxide synthases (NOS) activity with prolonged exposure to hind limb suspension. The effects of NOS inhibition during orthostasis on blood pressure regulation in those with chronic tetraplegia may provide insight into effective pharmacological therapy to reduce or prevent pathologic orthostatic changes. Treatment with a NOS inhibitor may facilitate the process of mobilization in those with acute higher cord lesions.

Interventional
Phase 2
Phase 3
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Crossover Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Hypotension
  • Spinal Cord Injury
  • Drug: N-Nitro L-arginine-methylester (L-NAME)
    A non-specific inhibitor of the nitric oxide synthase enzyme.
  • Procedure: Head-up Tilt maneuver
    Participant will be placed onto tilt table and brought to 15 degrees of head up tilt for 60 minutes (intravenous infusion time). After this time, a progressive increase to 45 degrees will be completed with a 10 degree increase every 5 minutes. Participant will remain at 45 degrees for 45 minutes or until symptom onset.
Placebo Comparator: Arm 1
Placebo control (normal saline) is employed on a separate visit during procedure.
Interventions:
  • Drug: N-Nitro L-arginine-methylester (L-NAME)
  • Procedure: Head-up Tilt maneuver

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
16
June 2010
June 2010   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • 18 to 65 year olds.
  • Non-ambulatory Chronic tetraplegia (1 year after acute SCI).

Exclusion Criteria:

  • central nervous system disease (other than SCI) e.g., multiple sclerosis, amyotrophic lateral sclerosis, syringomyelia, tabes dorsalis;
  • peripheral neuropathies;
  • surgical sympathectomy;
  • coronary heart and/or artery disease;
  • anemia;
  • hypertension;
  • renal function abnormalities;
  • diabetes mellitus;
  • pituitary insufficiency;
  • adrenal insufficiency;
  • hypothyroidism; and
  • medications known to affect the cardiovascular system.
Both
18 Years to 65 Years
Yes
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00237770
B3600-R
No
Department of Veterans Affairs
Department of Veterans Affairs
Not Provided
Principal Investigator: William Bauman, MD VA Medical Center, Bronx
Department of Veterans Affairs
April 2014

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