Prevention of Low Blood Pressure in Persons With Tetraplegia

Spinal Cord Injury Clinical Trial

Official title:

Prevention of Low Blood Pressure in Persons With Tetraplegia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00237770
• Other study ID #: B3600-R
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: October 7, 2005
• Last updated: April 23, 2014
• Start date: June 2003
• Est. completion date: June 2010

Study information

• Verified date: April 2014
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal GovernmentUnited States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: June 2010
• Est. primary completion date: June 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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.

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hypotension
• Quadriplegia
• Spinal Cord Injuries
• Spinal Cord Injury

Intervention

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.

Locations

Country	Name	City	State
United States	VA Medical Center, Bronx	Bronx	New York

Sponsors (1)

Lead Sponsor	Collaborator
VA Office of Research and Development

Country where clinical trial is conducted

United States, 

References & Publications (4)

Wecht JM, Radulovic M, Lafountaine MF, Rosado-Rivera D, Zhang RL, Bauman WA. Orthostatic responses to nitric oxide synthase inhibition in persons with tetraplegia. Arch Phys Med Rehabil. 2009 Aug;90(8):1428-34. doi: 10.1016/j.apmr.2009.02.004. — View Citation

Wecht JM, Radulovic M, Rosado-Rivera D, Zhang RL, LaFountaine MF, Bauman WA. Orthostatic effects of midodrine versus L-NAME on cerebral blood flow and the renin-angiotensin-aldosterone system in tetraplegia. Arch Phys Med Rehabil. 2011 Nov;92(11):1789-95. — View Citation

Wecht JM, Weir JP, Goldstein DS, Krothe-Petroff A, Spungen AM, Holmes C, Bauman WA. Direct and reflexive effects of nitric oxide synthase inhibition on blood pressure. Am J Physiol Heart Circ Physiol. 2008 Jan;294(1):H190-7. Epub 2007 Oct 26. — View Citation

Wecht JM, Weir JP, Krothe AH, Spungen AM, Bauman WA. Normalization of supine blood pressure after nitric oxide synthase inhibition in persons with tetraplegia. J Spinal Cord Med. 2007;30(1):5-9. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Systolic Blood Pressure During Head-up Tilt	Average systolic blood pressure over 45 minutes at 45 degrees of head-up tilt.	Average systolic blood pressure during head-up tilt (45 degrees) comparing active drug (L-NAME: 1.0 and 2.0 mg/kg) to placebo.	No