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

Recruiting in Palo Alto (17 mi)

+1 other location

Overseen byJill M Wecht, Ed.D

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Waitlist Available

Sponsor: James J. Peters Veterans Affairs Medical Center

No Placebo Group

Prior Safety Data

Trial Summary

What is the purpose of this trial?

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.

Research Team

Jill M Wecht, Ed.D

Principal Investigator

James J. Peters VA Medical Center

Eligibility Criteria

Inclusion Criteria

Spinal Cord Injured

Any level of injury

Any ASIA grade of SCI

See 2 more

Treatment Details

Interventions

Midodrine Hydrochloride (Alpha-1 Agonist)
Mirabegron (Beta-3 Agonist)
Placebo (Other)
Pyridostigmine Bromide (Acetylcholinesterase Inhibitor)

Participant Groups

2Treatment groups

Experimental Treatment

Group I: Study 2Experimental Treatment4 Interventions

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.

Group II: Study 1Experimental Treatment3 Interventions

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.

Midodrine Hydrochloride is already approved in Canada for the following indications: