Clinical trial NCT02307565: Blood Pressure, Cerebral Blood Flow and Cognition in Spinal Cord Injury
Official title: Blood Pressure, Cerebral Blood Flow and Cognition in SCI
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Spinal Cord Injury
Keywords: Midodrine
Blood pressure
Orthostatic hypotension
Spinal Cord Injury
Sympathetic vascular control
Cerebral blood flow velocity
Cognition function tasks
Quality of Life
MRI
fMRI
Lead sponsor: James J. Peters Veterans Affairs Medical Center
Sponsor class: FED
Collaborators: name: Kessler Foundation
First posted: 2014-12-04
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: Following spinal cord injury autonomic regulation of the cardiovascular system is impaired, which results in a variety of measurable abnormalities in blood pressure. Evidence of causality has been documented in the general medical literature with findings of improved cognitive function following acute increases in blood pressure using the anti-hypotensive agent Midodrine Hydrochloride (midodrine). Additionally, a recent report documented an inverse association between blood pressure and depression suggesting that low blood pressure may confer greater risk than high blood pressure. Midodrine is a drug approved by the Food and Drug Administration to treat low blood pressure in the general population. Midodrine is not approved in the United States to treat low blood pressure in persons with spinal cord injury. Therefore, its use in this study is investigational. The first objective is to characterize the relationship between blood pressure, cerebral blood flow velocity and cognitive function after a single dose of midodrine compared to placebo. Second objective is to determine the long-term safety and efficacy of midodrine administration.

Detailed description: Acute Study:The purpose of this research study is to measure a spinal cord injured individual's blood pressure and blood flow to the brain at rest and during thinking tasks before and after a single dose of midodrine, a drug used to treat low blood pressure (10 mg). Eligible participants will complete 2 visits to the laboratory. Visit 1, the subject will be given midodrine and Visit 2, the subject will be given a placebo. The order of the drug is random.

Observational Study:The purpose of this research study is to determine how blood pressure changes throughout the day in a spinal cord injured individual. There is no drug in this study. This study will last about 1 month and the subject will visit the laboratory 2 times, at the beginning and at the end of the month. The subject will be given a blood pressure monitor and will be asked to record his/her blood pressure at least 3 times a day. The laboratory visits will involve the participant discussing his/her monthly blood pressure recordings and experience with blood pressure monitor.

30-Day Crossover Study: The purpose of this research study is to determine the safety and efficacy of midodrine administration over a 30-day period of time. Midodrine is a drug approved by the Food and Drug Administration to treat low blood pressure in the general population. Midodrine is not approved in the United States to treat low blood pressure in persons with spinal cord injury. Therefore, its use in this study is investigational. The subject's participation will involve about 10 weeks and the subject will be asked to visit the laboratory 8 times. The subject will be asked to take midodrine for the first 30 days and after the 14 day washout period, the subject will be asked to take a placebo for 30 days. The order of the drug will be random. The subject and the study investigators will not know which drug the subject is receiving first and second during the 30 day-treatment phase. For visit 1,4, 5 and 8(Initial visits-start of new drug administration and Post Visits- end of new drug administration), the subject will complete many different thinking tasks while his/her blood pressure, heart rate and cerebral blood flow is taken. The subject will also complete quality of life surveys, autonomic dysreflexia surveys, and will take home a blood pressure monitor to continue to monitor blood pressure. For visit 2, 3, 6, and 7, the subject's blood pressure, cerebral blood flow and heart rate will be measured. Subject will also complete the autonomic dysreflexia survey.

30-Day Crossover \& MRI/Functional MRI (fMRI) Study: Eligible participants will in addition to completing the 30-Day Crossover study (procedure explained above), will also complete a MRI/fMRI Visit 1, 4, and 8.

Eligibility criteria: Inclusion Criteria:

Spinal Cord Injured

* Between the ages of 18-65 years old.
* Level of injury is between C1-T12
* Primarily wheelchair dependent for ambulation
* Have a spinal cord injury that is ASIA Impairment Scale (AIS) grade of A, B or C
* Injury occurred more than 1 year ago
* Low blood pressure (Systolic BP less than 110 mmHg for males, Systolic BP less than 100 mmHg for females)
* Primary language is English
* I am right handed

Exclusion Criteria:

* Currently have an illness or infection
* Severe history of AD (more than 3 symptomatic events per week, evidence of blood pressure elevations above 140/90 mmHg,significant adverse subjective symptoms reporting)
* Hypertension or diabetes
* 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
* Diagnosis of a psychiatric disorder such as post-traumatic stress disorder, schizophrenia or bipolar disorder
* Within the past 6 months, abused illicit drugs
* Pre-screen mini mental status exam score of less than 24, as rated by the researcher
* Vision is impaired- more than 20/60 in worst eye (with prescription eyewear)
* Coronary heart and/or artery disease
* Major surgery in the last 30 days
* Pregnant

Primary outcomes:
measure: Systolic Blood Pressure
timeFrame: 30 days
Secondary outcomes:
measure: Cerebral Blood Flow
timeFrame: 30 days
measure: Hopkins Verbal Learning Test
timeFrame: 30 days
measure: Number of Hypertensive Events
timeFrame: 30 days
Other outcomes:
Locations:
city: West Orange
country: United States
facility: Kessler Foundation Research Center
state: New Jersey
city: Bronx
country: United States
facility: James J Peters VAMC
state: New York
Study officials:
affiliation: JJPVAMC
name: Jill M Wecht, Ed.D
role: PRINCIPAL_INVESTIGATOR
affiliation: Kessler Foundation
name: Trevor Dyson-Hudson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Bloom O, Wecht JM, Legg Ditterline BE, Wang S, Ovechkin AV, Angeli CA, Arcese AA, Harkema SJ. Prolonged Targeted Cardiovascular Epidural Stimulation Improves Immunological Molecular Profile: A Case Report in Chronic Severe Spinal Cord Injury. Front Syst Neurosci. 2020 Oct 15;14:571011. doi: 10.3389/fnsys.2020.571011. eCollection 2020.
citation: Wecht JM, Weir JP, Katzelnick CG, Chiaravalloti ND, Kirshblum SC, Dyson-Hudson TA, Weber E, Bauman WA. Double-blinded, placebo-controlled crossover trial to determine the effects of midodrine on blood pressure during cognitive testing in persons with SCI. Spinal Cord. 2020 Sep;58(9):959-969. doi: 10.1038/s41393-020-0448-0. Epub 2020 Mar 17.