Spinal Cord Injury
Conditions
Keywords
Midodrine, Blood pressure, Orthostatic hypotension, Spinal Cord Injury, Sympathetic vascular control, Cerebral blood flow velocity, Cognition function tasks, Quality of Life, MRI, fMRI
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.
Interventions
DRUGMidodrine
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.
DRUGPlacebo
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.
Sponsors
Kessler Foundation
James J. Peters Veterans Affairs Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Systolic Blood Pressure | 30 days | Seated systolic blood pressure following midodrine administration compared to placebo. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cerebral Blood Flow | 30 days | Middle cerebral artery blood flow velocity following midodrine administration compared to placebo. |
| Hopkins Verbal Learning Test | 30 days | Memory score on the Hopkins Verbal Learning Test following midodrine administration compared to placebo. Higher score is better, range from 0 to 36. |
| Number of Hypertensive Events | 30 days | Number of daily systolic blood pressure recordings above 140 mmHg following midodrine administration compared to placebo. |
Countries
United States
Participant flow
Pre-assignment details
Number of participants eligible for study was only 19.
Participants by arm
| Arm | Count |
|---|---|
| Midodrine/Placebo Arm 1 last 30 days. Subject will be given midodrine during arm 1 and placebo during arm 2.
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. | 8 |
| Placebo/Midodrine Arm 2 last 30 days. Subject will be given placebo during arm 1 and midodrine during arm 2.
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. | 11 |
| Total | 19 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 2 |
| Overall Study | Withdrawal by Subject | 2 | 2 |
Baseline characteristics
| Characteristic | Placebo/Midodrine | Total | Midodrine/Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 11 Participants | 19 Participants | 8 Participants |
| Age, Continuous | 42.4 years STANDARD_DEVIATION 10.2 | 41.5 years STANDARD_DEVIATION 10.3 | 40.4 years STANDARD_DEVIATION 11 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 4 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 6 Participants | 11 Participants | 5 Participants |
| Region of Enrollment United States | 11 participants | 19 participants | 8 participants |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 8 Participants | 14 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 19 | 0 / 19 |
| other Total, other adverse events | 5 / 19 | 0 / 19 |
| serious Total, serious adverse events | 0 / 19 | 0 / 19 |
Outcome results
Primary
Systolic Blood Pressure
Seated systolic blood pressure following midodrine administration compared to placebo.
Time frame: 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Midodrine | Systolic Blood Pressure | 116.3 mmHg | Standard Deviation 22.7 |
| Placebo | Systolic Blood Pressure | 98.0 mmHg | Standard Deviation 23.3 |
Secondary
Cerebral Blood Flow
Middle cerebral artery blood flow velocity following midodrine administration compared to placebo.
Time frame: 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Midodrine | Cerebral Blood Flow | 45.08 cm/sec | Standard Deviation 12.87 |
| Placebo | Cerebral Blood Flow | 43.97 cm/sec | Standard Deviation 16.7 |
Secondary
Hopkins Verbal Learning Test
Memory score on the Hopkins Verbal Learning Test following midodrine administration compared to placebo. Higher score is better, range from 0 to 36.
Time frame: 30 days
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Midodrine | Hopkins Verbal Learning Test | -3.56 score on a scale | Standard Deviation 4.16 |
| Placebo | Hopkins Verbal Learning Test | -2.27 score on a scale | Standard Deviation 6.47 |
Secondary
Number of Hypertensive Events
Number of daily systolic blood pressure recordings above 140 mmHg following midodrine administration compared to placebo.
Time frame: 30 days
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Midodrine | Number of Hypertensive Events | 112 blood pressure recordings |
| Placebo | Number of Hypertensive Events | 50 blood pressure recordings |