Prevention of Low Blood Pressure in Persons With Tetraplegia

NCT ID: NCT00237770

Last Updated: 2014-05-19

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 16 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2003-06-30
• Study Completion Date: 2010-06-30

Brief 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.

Detailed 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.

Conditions

Hypotension; Spinal Cord Injury

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Arm 1

Placebo control (normal saline) is employed on a separate visit during procedure.

Group Type: PLACEBO_COMPARATOR

N-Nitro L-arginine-methylester (L-NAME)

Intervention Type: DRUG

A non-specific inhibitor of the nitric oxide synthase enzyme.

Head-up Tilt maneuver

Intervention Type: PROCEDURE

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.

Interventions

N-Nitro L-arginine-methylester (L-NAME)

A non-specific inhibitor of the nitric oxide synthase enzyme.

Intervention Type: DRUG

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.

Intervention Type: PROCEDURE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

US Department of Veterans Affairs

FED

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

William Bauman, MD

Role: PRINCIPAL_INVESTIGATOR

VA Medical Center, Bronx

Locations

VA Medical Center, Bronx

The Bronx, New York, United States

Countries

United States

References

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. doi: 10.1080/10790268.2007.11753907.

Reference Type: RESULT

PMID: 17385265 (View on PubMed)

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. doi: 10.1152/ajpheart.00366.2007. Epub 2007 Oct 26.

Reference Type: RESULT

PMID: 17965289 (View on PubMed)

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.

Reference Type: RESULT

PMID: 19651280 (View on PubMed)

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. doi: 10.1016/j.apmr.2011.03.022. Epub 2011 Jul 16.

Reference Type: RESULT

PMID: 21762873 (View on PubMed)

La Fountaine MF, Wecht JM, Bauman WA. Acute nitric oxide synthase inhibition and cardiac conduction in persons with spinal cord injury: a short report. Pharmazie. 2013 Apr;68(4):245-50.

Reference Type: DERIVED

PMID: 23700789 (View on PubMed)

Other Identifiers

B3600-R

Identifier Type: -

Identifier Source: org_study_id