Blood Pressure, Cerebral Blood Flow and Cognition in Spinal Cord Injury

Spinal Cord Injury Clinical Trial

Official title:

Blood Pressure, Cerebral Blood Flow and Cognition in SCI

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02307565
• Other study ID #: WEC-13-066
• Status: Completed
• Phase: Phase 3
• Start date: March 2014
• Est. completion date: December 2019

Study information

• Verified date: June 2023
• Source: James J. Peters Veterans Affairs Medical Center
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 2019
• Est. primary completion date: December 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Spinal Cord Injuries
• Spinal Cord Injury

Intervention

Drug:
• Midodrine
Each arm (2) will last 30 days with a 14 day washout in between each arm. Subjects nor the investigators will know which drug (midodrine or placebo) is administered to the subject for the first arm (30 days) and the second arm (30 days). The subjects will take a pill three times a day. Each subject will return home with a blood pressure monitor and will be asked to report his/her blood pressure at least 3 times a day and complete questionnaires based on how he/she is feeling.
• Placebo
Each arm (2) will last 30 days with a 14 day washout in between each arm. Subjects nor the investigators will know which drug (midodrine or placebo) is administered to the subject for the first arm (30 days) and the second arm (30 days). The subjects will take a pill three times a day. Each subject will return home with a blood pressure monitor and will be asked to report his/her blood pressure at least 3 times a day and complete questionnaires based on how he/she is feeling.

Locations

Country	Name	City	State
United States	James J Peters VAMC	Bronx	New York
United States	Kessler Foundation Research Center	West Orange	New Jersey

Sponsors (2)

Lead Sponsor	Collaborator
James J. Peters Veterans Affairs Medical Center	Kessler Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Systolic Blood Pressure	Seated systolic blood pressure following midodrine administration compared to placebo.	Up to 3 years
Secondary	Cerebral Blood Flow	Middle cerebral artery blood flow velocity following midodrine administration compared to placebo.	Up to 3 years
Secondary	Memory	Memory score on the Hopkins Verbal Learning Test following midodrine administration compared to placebo.	Up to 3 years
Secondary	Number of Hypertensive Events	Number of daily blood pressure recordings above 140/90 mmHg following midodrine administration compared to placebo.	Up to 3 years