A Phase 2 interventional study of Midodrine Hydrochloride and Pyridostigmine Bromide in Spinal Cord Injury, Autonomic Dysreflexia and Baroreceptor Integrity, sponsored by James J. Peters Veterans Affairs Medical Center. Completed at 2 sites in United States. Open to participants aged 18 Years to 85 Years. Per ClinicalTrials.gov, last updated 2024-10-01.
Sponsored by James J. Peters Veterans Affairs Medical Center · Phase 2, Interventional, and Treatment
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.
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.
1,988 studies on the registry are indexed under Spinal Cord Injuries; 516 are open to participants now.
This study's enrollment of 21 is below the median of 24 across 1,594 interventional studies indexed under Spinal Cord Injuries.
Browse Spinal Cord Injuries studies →James J. Peters Veterans Affairs Medical Center is the lead sponsor of 50 studies on the registry; 4 are open to participants now.
Of its 8 completed or terminated interventional studies of FDA-regulated products, 2 (25%) have results posted.
Counted across the registry records on this site, refreshed daily.
Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.
Spinal Cord Injured
Exclusion Criteria:
Study 1: is a dose escalation to determine the individualized dose of each of 3 medications (midodrine, pyridostigmine, mirabegron) that increases SBP into the normal range (111-139 mmHg). The investigator will be using midodrine hydrochloride, pyridostigmine bromide and mirabegron.
Drug: Midodrine Hydrochloride · Drug: Pyridostigmine Bromide · Drug: Mirabegron
Study2: is a randomized placebo-controlled double-blinded investigation to determine the effect of the normalization of SBP on cerebral blood flow, cognitive function (memory and attention processing) and quality of life. The investigator will be using midodrine hydrochloride, pyridostigmine bromide, mirabegron and placebo.
Drug: Midodrine Hydrochloride · Drug: Pyridostigmine Bromide · Drug: Mirabegron · Other: Placebo
study 1 will be single blind. study 2 will be blinded randomized-control trial.
Also known as: midodrine
study 1 will be single blind. study 2 will be blinded randomized-control trial.
Also known as: pyridostigmine
study 1 will be single blind. study 2 will be blinded randomized-control trial.
placebo will only be used for study arm 2, the randomized blinded phase.
Systolic Blood Pressure
Seated systolic blood pressure following intervention administration.
Time frame: 4 hours
Number of Participants With Normal Blood Pressure Readings
Number of participants with a systolic blood pressure readings between 111-139 mmHg in response to each of the four conditions: 1. Placebo 2. Midodrine 3. Mirabegron 4. Pyridostigmine
Time frame: 4 hours
| Milestone | Study 1 |
|---|---|
| Started | 21 |
| Midodrine (low) | 19 |
| Midodrine (medium) | 6 |
| Midodrine (high) | 0 |
| Mirabegron (low) | 19 |
| Mirabegron (medium) | 15 |
| Mirabegron (high) | 8 |
| Pyridostigmine (low) | 19 |
| Pyridostigmine (medium) | 10 |
| Pyridostigmine (high) | 5 |
| Placebo | 0 |
| Completed | 19 |
| Not completed | 2 |
| Milestone | Study 1 |
|---|---|
| Started | 18 |
| Midodrine (low) | 11 |
| Midodrine (medium) | 5 |
| Midodrine (high) | 0 |
| Mirabegron (low) | 3 |
| Mirabegron (medium) | 7 |
| Mirabegron (high) | 7 |
| Pyridostigmine (low) | 7 |
| Pyridostigmine (medium) | 5 |
| Pyridostigmine (high) | 5 |
| Placebo | 16 |
| Completed | 16 |
| Not completed | 2 |
Seated systolic blood pressure following intervention administration.
| mmHg | Study 2: Placebo | Study 2: Midodrine | Study 2: Mirabegron | Study 2: Pyridostigmine |
|---|---|---|---|---|
| Systolic Blood Pressure | 93.21 ± 9.01 | 107.00 ± 11.07 | 95.8 ± 9.5 | 93.84 ± 9.69 |
Number of participants with a systolic blood pressure readings between 111-139 mmHg in response to each of the four conditions: 1. Placebo 2. Midodrine 3. Mirabegron 4. Pyridostigmine
| Participants | Study 2: Placebo | Study 2: Midodrine | Study 2: Mirabegron | Study 2:Pyridostigmine |
|---|---|---|---|---|
| Number of Participants With Normal Blood Pressure Readings | 4 | 14 | 6 | 5 |
Collected over For the duration of the study (4-hours).. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Midodrine (Low) | 0/19 (0%) | 0/19 (0%) | 0/19 (0%) |
| Midodrine (Mid) | 0/6 (0%) | 0/6 (0%) | 0/6 (0%) |
| Midodrine (High) | — | — | — |
| Mirabegron (Low) | 0/19 (0%) | 0/19 (0%) | 0/19 (0%) |
| Mirabegron (Mid) | 0/15 (0%) | 0/15 (0%) | 0/15 (0%) |
| Mirabegron (hi) | 0/8 (0%) | 0/8 (0%) | 0/8 (0%) |
| Pyridostigmine (Low) | 0/19 (0%) | 0/19 (0%) | 0/19 (0%) |
| Pyridostigmine (Mid) | 0/10 (0%) | 0/10 (0%) | 0/10 (0%) |
| Pyridostigmine (hi) | 0/5 (0%) | 0/5 (0%) | 0/5 (0%) |
| Placebo | 0/16 (0%) | 0/16 (0%) | 0/16 (0%) |
| Age, Categorical(Participants) | Study 1 |
|---|---|
| <=18 years | 0 |
| Between 18 and 65 years | 21 |
| >=65 years | 0 |
| Age, Continuous(years) | Study 1 |
|---|---|
| Mean | 40.47 ± 10.08 |
| Sex: Female, Male(Participants) | Study 1 |
|---|---|
| Female | 7 |
| Male | 14 |
| Race (NIH/OMB)(Participants) | Study 1 |
|---|---|
| American Indian or Alaska Native | 0 |
| Asian | 1 |
| Native Hawaiian or Other Pacific Islander | 0 |
| Black or African American | 4 |
| White | 16 |
| More than one race | 0 |
| Unknown or Not Reported | 0 |
| Region of Enrollment(participants) | Study 1 |
|---|---|
| United States | 21 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Undecided
This study is completed, as verified in Sep 2024. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Studies of the drugs tested here: Midodrine · Pyridostigmine · Mirabegron
James J. Peters Veterans Affairs Medical Center