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

NCT02893553 | Completed Phase 2 Results

• 1 other identifier: WEC-16-015
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 2

Brief 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

Outcome Measures

Primary Outcomes (2)

• Systolic Blood Pressure

  Seated systolic blood pressure following intervention administration.

  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

  4 hours

Study Arms (2)

Study 1

EXPERIMENTAL

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

Study 2

EXPERIMENTAL

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

Interventions

Midodrine Hydrochloride DRUG

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

Also known as: midodrine

Study 1; Study 2

Pyridostigmine Bromide DRUG

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

Also known as: pyridostigmine

Study 1; Study 2

Mirabegron DRUG

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

Study 1; Study 2

Placebo OTHER

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

Study 2

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• James J. Peters Veterans Affairs Medical Center: lead
• Kessler Foundation: collaborator

Study Sites (2)

Kessler Foundation Research Center

West Orange, New Jersey, 07052, United States

Location

James J Peters VAMC

The Bronx, New York, 10468, United States

Location

MeSH Terms

Conditions

Spinal Cord Injuries; Autonomic Dysreflexia

Interventions

Midodrine; Pyridostigmine Bromide; mirabegron

Condition Hierarchy (Ancestors)

Spinal Cord Diseases; Central Nervous System Diseases; Nervous System Diseases; Trauma, Nervous System; Wounds and Injuries; Autonomic Nervous System Diseases

Intervention Hierarchy (Ancestors)

Ethanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Amines; Pyridinium Compounds; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Dr. Jill Wecht
• Organization: James J Peters VAMC

jm.wecht@va.gov

718-584-9000

Study Officials

• Jill M Wecht, Ed.D

  James J. Peters VA Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: FED
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Health Scientist

Study Record Dates

• First Submitted: August 29, 2016
• First Posted: September 8, 2016
• Study Start: December 1, 2016
• Primary Completion: December 1, 2021
• Study Completion: December 1, 2021
• Last Updated: October 1, 2024
• Results First Posted: October 1, 2024

Record last verified: 2024-09

Locations

US (2)