Orthostatic Hypotension, Spinal Cord Injury
Conditions
Keywords
Spinal Cord Injury, Orthostatic Hypotension, Blood Pressure, Midodrine Hydrochloride, L-NAME
Brief summary
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.
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.
Interventions
DRUGL-NAME
A non-selective inhibitor of nitric oxide synthase and placebo. It has been used experimentally to induce hypertension.
DRUGMidodrine
To treat low blood pressure.
DRUGPlacebo
A pill with an inactive substance that looks like the study drug.
Sponsors
US Department of Veterans Affairs
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Blood Pressure | Blood pressure during the 4 hour period after no drug, L-NAME (IV: 1.0 mg/kg) and midodrine (PO: 10.0 mg) administration |
Countries
United States
Participant flow
Recruitment details
34 subjects were consented 24 completed testing. Subjects were recruited through the Center of Excellence for the Medical Consequences of Spinal Cord Injury (SCI) from June 2010 to August of 2013.
Pre-assignment details
Eligibility criteria were covered by the study coordinator prior to enrollment.
Participants by arm
| Arm | Count |
|---|---|
| All Participants All participants were studied on three laboratory visits and underwent seated blood pressure assessment before and after administration of Midodrine, L-NAME or placebo, which were given in random order. | 34 |
| Total | 34 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 34 Participants |
| Age, Continuous | 40 years STANDARD_DEVIATION 12 |
| Region of Enrollment United States | 34 participants |
| Sex: Female, Male Female | 7 Participants |
| Sex: Female, Male Male | 27 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 0 / 15 | 0 / 9 | 0 / 15 | 0 / 9 | 0 / 15 | 0 / 9 |
| serious Total, serious adverse events | 0 / 15 | 0 / 9 | 0 / 15 | 0 / 9 | 0 / 15 | 0 / 9 |
Outcome results
Primary
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
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Arm 1A | Blood Pressure | 120 mmHg | Standard Deviation 17 |
| Arm 1B | Blood Pressure | 112 mmHg | Standard Deviation 10 |
| Arm 2A | Blood Pressure | 117 mmHg | Standard Deviation 19 |
| Arm 2B | Blood Pressure | 109 mmHg | Standard Deviation 5 |
| Arm 3A | Blood Pressure | 96 mmHg | Standard Deviation 12 |
| Arm 3B | Blood Pressure | 109 mmHg | Standard Deviation 6 |