Acetylcholinesterase Inhibition and Orthostatic Hypotension in SCI
Condition: Hypotension, Postural
MeSH terms: Hypotension, Orthostatic; Hypotension
Intervention: Pyridostigmine Bromide; Tilt table test
Intervention description: After being transferred onto a tilt table, subject will lie in a rested, supine position in which the study drug, pyridostigmine bromide will be administered at the 30 minute time point. Following the administration of the study drug, the subject will remain in the supine position for an additional 30 minutes until the tilting protocol commences.; After 60 minutes in supine resting position, a progressive head-up tilt will be utilized in which the table will be adjusted to 15°, 25°, 35° for 5 minutes at each angle and then maintained at 45° for 45 minutes or until the subjects experiences symptoms of compromised cerebral blood flow, which include, but are not limited to, light headedness, blurry vision, dizziness and nausea.
Intervention MeSH terms: Bromides; Pyridostigmine Bromide
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 10.0
Sex: All
Minimum age: 18 Years
Maximum age: 65 Years
Healthy volunteers: No
Keywords: Hypotension, Postural

Summary:

      Due to de-centralized cardiovascular control, persons with spinal cord injury (SCI)
      experience blood pressure (BP) dysregulation which manifests in chronic hypotension with
      exacerbation during orthostatic positioning. Although many individuals with SCI remain
      asymptomatic to hypotension and orthostatic hypotension (OH), we recently reported reduced
      memory and marginally reduced attention and processing speed in hypotensive individuals with
      SCI compared to a normotensive cohort. Thus, we believe that treatment of overtly
      asymptomatic hypotension and OH in the SCI population is clinically warranted. Currently the
      FDA has approved only midodrine hydrochloride for the treatment of dizziness associated with
      OH and proof of efficacy is limited. Acetylcholinesterase inhibition for treatment of OH is a
      novel concept and has gained recent recognition in models of neurogenic OH (multiple system
      atrophy; pure autonomic failure, diabetic neuropathy). The physiological rationale of this
      concept is unique: acetylcholine (AcH) is the pre-ganglionic neurotransmitter of the
      sympathetic nervous system. Inhibition of acetylcholinesterase will limit the breakdown of
      AcH thereby facilitating vascular adrenergic tone and peripheral vasoconstriction.
      Acetylcholinesterase inhibition has been reported to be efficacious in models of both
      pre-ganglionic (multiple system atrophy) and post-ganglionic (pure autonomic failure,
      diabetic neuropathy) origin and persons with SCI reflect a model of a preganglionic disorder.
      In theory, if an individual has a complete autonomic lesion, acetylcholinesterase inhibition
      would not be expected to improve orthostatic BP because little/no neural traffic would be
      transmitted to the pre-synapse. However, individuals with an incomplete autonomic lesion may
      benefit from this class of agent. Researchers are currently investigating the orthostatic BP
      effects of acetylcholinesterase inhibition with pyridostigmine bromide (60 mg) in 10
      individuals with SCI.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18-65 years old

          -  Spinal cord injury with American Spinal Injury Association Impairment Scale (AIS)
             level of Grade A, B, C or D 9non-ambulatory)

          -  Neurological level of injury C3-T2

          -  Duration of injury greater than 1 year

        Exclusion Criteria:

          -  Currently taking medications with known blood pressure raising or lowering effects.

          -  Taking over-the-counter medications for allergies or cold symptoms 24-hours prior to
             testing.

          -  I have a C3 level of injury and I am ventilator dependent.

          -  History of cardiovascular arrhythmias (especially slow heart rate, less than 45 bpm),
             block in the electrical signal within the heart, cardiac arrest.

          -  History of convulsions or seizures.

          -  Currently taking medication to treat active asthma.

          -  Thyroid problems.

          -  Current smoker.

          -  Known coronary heart and/or artery disease.

          -  High blood pressure

          -  Diabetes

          -  Current illness or infection

          -  Major surgery in the last 30 days

          -  Hypersensitivity to pyridostigmine, bromides, or any component of the formulation; (as
             determined by review of known drug allergies reported in the medical history intake
             form and confirmed by the study physician)

          -  Pregnancy