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

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.

Conditions

• Spinal Cord Injury
• Autonomic Dysreflexia
• Baroreceptor Integrity
• Sympathetic Integrity
• Vagal Integrity
• Autonomic Integrity
• Hypotensive
• Cognitive Function
• Cerebral Blood Flow
• Blood Pressure

Interventions

DRUG

Midodrine Hydrochloride

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

DRUG

Pyridostigmine Bromide

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

DRUG

Mirabegron

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

OTHER

Placebo

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

Sponsors & Collaborators

• Kessler Foundation

  collaborator OTHER

• James J. Peters Veterans Affairs Medical Center

  lead FED

Principal Investigators

• Jill M Wecht, Ed.D · James J. Peters VA Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

DOUBLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

85 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-12-31

Primary Completion

2021-12-31

Completion

2021-12-31

Countries

• United States

Study Locations