Blood Pressure, Cerebral Blood Flow and Cognition in Spinal Cord Injury
Condition: Spinal Cord Injury
MeSH terms: Spinal Cord Injuries
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Midodrine; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): 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.; 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.
Other intervention name(s): Midodrine or Placebo; Midodrine or Placebo
Intervention MeSH terms: Midodrine
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Midodrine; Blood pressure; Orthostatic hypotension; Spinal Cord Injury; Sympathetic vascular control; Cerebral blood flow velocity; Cognition function tasks; Quality of Life; MRI; fMRI