Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT02893553 |
Other study ID # |
WEC-16-015 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 2
|
First received |
|
Last updated |
|
Start date |
December 2016 |
Est. completion date |
December 2021 |
Study information
Verified date |
June 2023 |
Source |
James J. Peters Veterans Affairs Medical Center |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
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.
Description:
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.