The Effects of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive Individuals With Spinal Cord Injury
| Status: | Recruiting |
|---|---|
| Conditions: | Cognitive Studies, Cognitive Studies, High Blood Pressure (Hypertension), Cardiology, Hospital, Hospital, Orthopedic |
| Therapuetic Areas: | Cardiology / Vascular Diseases, Psychiatry / Psychology, Orthopedics / Podiatry, Other |
| Healthy: | No |
| Age Range: | 18 - 85 |
| Updated: | 3/2/2019 |
| Start Date: | December 2016 |
| End Date: | December 2019 |
| Contact: | Alexander T Lombard, MS |
| Email: | alombard@kesslerfoundation.org |
| Phone: | 973-324-3588 |
Dysregulation of blood pressure (BP), secondary to decentralized autonomic nervous system
(ANS) control of the cardiovascular system, often results in chronic hypotension and
orthostatic hypotension (OH) in persons with spinal cord injury (SCI), particularly in those
with high cord lesions (i.e., above T6). While most hypotensive individuals with chronic SCI
remain asymptomatic and do not complain of symptoms associated with cerebral hypoperfusion,
evidence of reduced resting cerebral blood flow (CBF) has been reported in association with
low systemic BP in the SCI and non-SCI populations. Reduced CBF in hypotensive individuals
may lead to cognitive dysfunction, and we reported significantly impaired memory and
marginally impaired attention processing in hypotensive individuals with SCI compared to a
normotensive SCI cohort. Furthermore, we found that CBF was not increased during cognitive
testing in individuals with SCI, which may contribute to impaired cognitive function compared
to non-SCI controls. Although asymptomatic hypotension may have an adverse impact on
cognitive function and quality of quality of life (QOL) clinical management of this condition
is extremely low. In fact, we reported that while nearly 40% of Veterans with SCI were
hypotensive, less than 1% carried the diagnosis of hypotension or were prescribed an
anti-hypotensive medication. The discrepancy between incidence and treatment of asymptomatic
hypotension in the SCI population may relate to a paucity of treatment options which are
supported by rigorous clinical trials documenting safe and effective use of anti-hypotensive
therapy on BP, CBF and cognitive function. We hypothesize these study medications may
increase systolic blood pressure to the normal range and improve cerebral blood flow
velocity. Results and conclusions will not be removed from the record.
(ANS) control of the cardiovascular system, often results in chronic hypotension and
orthostatic hypotension (OH) in persons with spinal cord injury (SCI), particularly in those
with high cord lesions (i.e., above T6). While most hypotensive individuals with chronic SCI
remain asymptomatic and do not complain of symptoms associated with cerebral hypoperfusion,
evidence of reduced resting cerebral blood flow (CBF) has been reported in association with
low systemic BP in the SCI and non-SCI populations. Reduced CBF in hypotensive individuals
may lead to cognitive dysfunction, and we reported significantly impaired memory and
marginally impaired attention processing in hypotensive individuals with SCI compared to a
normotensive SCI cohort. Furthermore, we found that CBF was not increased during cognitive
testing in individuals with SCI, which may contribute to impaired cognitive function compared
to non-SCI controls. Although asymptomatic hypotension may have an adverse impact on
cognitive function and quality of quality of life (QOL) clinical management of this condition
is extremely low. In fact, we reported that while nearly 40% of Veterans with SCI were
hypotensive, less than 1% carried the diagnosis of hypotension or were prescribed an
anti-hypotensive medication. The discrepancy between incidence and treatment of asymptomatic
hypotension in the SCI population may relate to a paucity of treatment options which are
supported by rigorous clinical trials documenting safe and effective use of anti-hypotensive
therapy on BP, CBF and cognitive function. We hypothesize these study medications may
increase systolic blood pressure to the normal range and improve cerebral blood flow
velocity. Results and conclusions will not be removed from the record.
Study 1: Subjects will visit the laboratory between 3 and 9 times for 4 hours to determine
the BP response to each dose of the 3 study medications (midodrine, pyridostigmine, and
mirabegron). Upon arrival to the laboratory subjects will be randomized to receive midodrine,
pyridostigmine, or mirabegron. Subjects will remain seated in their wheelchair for the
duration of testing. Instrumentation will be applied by study personnel while subject is
seated quietly, this can take up to 20 minutes. Instrumentation includes placement of 3 ECG
electrodes for continuous HR monitoring and finger and brachial BP cuffs. BP, BR and HR will
be recorded for 5-minutes before medication administration (baseline). After baseline, a
small pill will be given with a glass of water. BP, BR and HR will be monitored for 5-minutes
every 30 minutes for 4 hours after drug administration.
Study 2: Twenty will visit the laboratory on 4 occasions to determine the effects of three
anti-hypotensive agents, compared to placebo, on BP, CBFv, and cognitive performance on
selected neuropsychological tests. Upon arrival to the laboratory for every visit subjects
will be randomized to receive midodrine, pyridostigmine, mirabegron, or matching placebo.
Neither the study subject nor the investigator will know which is being administered.
Subjects will remain seated in their wheelchair throughout the duration of the study session
and will be closely monitored by study personnel. Instrumentation will include placement of 3
ECG electrodes for continuous heart rate (HR) monitoring, finger and brachial BP cuffs, and a
Doppler ultrasound probe positioned at the left MCA for continuous CBFv monitoring. Subjects
will remain quietly seated in their wheelchair for 30-minutes after instrumentation for a
5-minute recording of continuous HR, BP, and CBFv (baseline). Prior to the baseline data
collection period, the first battery of cognitive tests will be administered. The study
medication will be administered to the subject along with a glass of water approximately
30-minutes after arrival to the laboratory. There will be a 2 hour break period until the
second cognitive battery begins.
the BP response to each dose of the 3 study medications (midodrine, pyridostigmine, and
mirabegron). Upon arrival to the laboratory subjects will be randomized to receive midodrine,
pyridostigmine, or mirabegron. Subjects will remain seated in their wheelchair for the
duration of testing. Instrumentation will be applied by study personnel while subject is
seated quietly, this can take up to 20 minutes. Instrumentation includes placement of 3 ECG
electrodes for continuous HR monitoring and finger and brachial BP cuffs. BP, BR and HR will
be recorded for 5-minutes before medication administration (baseline). After baseline, a
small pill will be given with a glass of water. BP, BR and HR will be monitored for 5-minutes
every 30 minutes for 4 hours after drug administration.
Study 2: Twenty will visit the laboratory on 4 occasions to determine the effects of three
anti-hypotensive agents, compared to placebo, on BP, CBFv, and cognitive performance on
selected neuropsychological tests. Upon arrival to the laboratory for every visit subjects
will be randomized to receive midodrine, pyridostigmine, mirabegron, or matching placebo.
Neither the study subject nor the investigator will know which is being administered.
Subjects will remain seated in their wheelchair throughout the duration of the study session
and will be closely monitored by study personnel. Instrumentation will include placement of 3
ECG electrodes for continuous heart rate (HR) monitoring, finger and brachial BP cuffs, and a
Doppler ultrasound probe positioned at the left MCA for continuous CBFv monitoring. Subjects
will remain quietly seated in their wheelchair for 30-minutes after instrumentation for a
5-minute recording of continuous HR, BP, and CBFv (baseline). Prior to the baseline data
collection period, the first battery of cognitive tests will be administered. The study
medication will be administered to the subject along with a glass of water approximately
30-minutes after arrival to the laboratory. There will be a 2 hour break period until the
second cognitive battery begins.
Inclusion Criteria:
Spinal Cord Injured
- Any level of injury
- Any ASIA grade of SCI
- Primarily wheelchair dependent for mobility
- Duration of injury ˃ 1 year
Exclusion Criteria:
- Current illness or infection
- History of severe autonomic dysreflexia (AD: condition where BP increases)
- More than 3 symptomatic events per week; BP elevations above 140/90 mmHg; adverse
symptoms reporting (e.g., light headedness, dizziness, goosebumps, chills, nausea,
etc.)
- Diagnosis of hypertension
- History of Traumatic Brain Injury (TBI)
- Documented history of traumatic brain injury (TBI)
- Neurological condition other than SCI (Alzheimer's disease, dementia, stroke, multiple
sclerosis, Parkinson's disease, etc)
- History of epilepsy or other seizure disorder
- Liver or kidney disease
- Bladder problems including blockage of the urine and/or weak urine stream
- Diagnosis of a psychiatric disorder such as schizophrenia or bipolar disorder
- Diagnosis of artery disease, heart failure, irregular heartbeat, and AV block
- Allergies to aspirin, a yellow dye, pyridostigmine bromide, midodrine hydrochloride,
lyethylene oxide, polyethylene glycol, hydroxypropyl cellulose, butylated
hydroxytoluene, magnesium stearate, hypromellose, yellow ferric oxide, and red ferric
oxide
- Had major surgery in the last 30 days
- Illicit drug abuse within the last 6 months
- Pregnant
We found this trial at
2
sites
West Orange, New Jersey 07052
Principal Investigator: Jill M Wecht
Phone: 973-324-3588
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Bronx, New York 10468
Principal Investigator: Jill M Wecht, EdD
Phone: 718-584-9000
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