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Spinal Cord InjuryPhase 2NCT02893553

The Effects of Normalizing Blood Pressure on Cerebral Blood Flow in Hypotensive Individuals With Spinal Cord Injury

A Phase 2 study testing Midodrine Hydrochloride, Pyridostigmine Bromide and Mirabegron in people with Spinal Cord Injury and Autonomic Dysreflexia, run by James J. Peters Veterans Affairs Medical Center at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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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). Read more about this study

Who is it for?
Ages 18 to 85 years
What is being tested?
Midodrine Hydrochloride, Pyridostigmine Bromide and Mirabegron
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
21 participants
Where
2 sitesUnited States
Study dates
Dec 2016to Dec 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Spinal Cord Injured
  • Any level of injury
  • Any ASIA grade of SCI
  • Primarily wheelchair dependent for mobility
  • Duration of injury ˃ 1 year

Who cannot join

  • 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)
Show all 16Show fewer
  • 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

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • James J Peters VAMC

    The Bronx, New York, 10468

  • Kessler Foundation Research Center

    West Orange, New Jersey, 07052

Other trials in United States

About this study

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.

Read the detailed 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.

Being tested
Midodrine Hydrochloride, Pyridostigmine Bromide, Mirabegron, Placebo
Medical subject headings
Spinal Cord Injuries, Autonomic Dysreflexia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Midodrine HydrochlorideDrug

    Also called midodrine

    study 1 will be single blind. study 2 will be blinded randomized-control trial.

  • Pyridostigmine BromideDrug

    Also called pyridostigmine

    study 1 will be single blind. study 2 will be blinded randomized-control trial.

  • MirabegronDrug

    study 1 will be single blind. study 2 will be blinded randomized-control trial.

  • PlaceboOther

    placebo will only be used for study arm 2, the randomized blinded phase.

Study groups in NCT02893553
Study groupRoleWhat they receive
Study 1ExperimentalStudy 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.
Receives: Drug: Midodrine Hydrochloride; Drug: Pyridostigmine Bromide; Drug: Mirabegron
Study 2ExperimentalStudy2: 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.
Receives: Drug: Midodrine Hydrochloride; Drug: Pyridostigmine Bromide; Drug: Mirabegron; Other: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Systolic Blood Pressure

    Seated systolic blood pressure following intervention administration.

    Measured: 4 hours

  2. 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

    Measured: 4 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted8 Sep 2016 (estimated)
  2. Study startDec 2016
  3. Primary completionDec 2021
  4. Study completionDec 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02893553
Sponsor's protocol ID
WEC-16-015
Status last verified
Sep 2024
First submitted
29 Aug 2016
Last updated
1 Oct 2024
Data monitoring committee
No
Individual data sharing
Undecided

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Midodrine Hydrochloride, Pyridostigmine Bromide and Mirabegron in people with Spinal Cord Injury and Autonomic Dysreflexia, run by James J. Peters Veterans Affairs Medical Center at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 1 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 1 Oct 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Systolic Blood Pressure (time frame: 4 hours). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02893553.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 1 Oct 2024.

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