Phase 2
N=10
Acetylcholinesterase Inhibition and Orthostatic Hypotension in SCI
Hypotension, Postural
Bottom Line
View on ClinicalTrials.gov: NCT02307526 ↗Enrolled (actual)
10
Serious AEs
10.0%
Results posted
Jul 2017
Primary outcome: Primary: Systolic Blood Pressure — 97; 103; 90; 88 mm Hg
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Pyridostigmine Bromide (Drug); Tilt table test (Device)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- James J. Peters Veterans Affairs Medical Center
- Primary completion
- Mar 2015
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Systolic Blood Pressure |
97; 103; 90; 88 | — |
| PRIMARY Diastolic Blood Pressure |
64; 66; 64; 63 | — |
| PRIMARY Heart Rate |
52; 55; 66; 72 | — |
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
Data sourced from ClinicalTrials.gov (NCT02307526). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.