Phenytoin as a Neuroprotective Agent Against Corticosteroid-induced Functional Imaging Changes
Condition: Healthy
Intervention: Phenytoin (brand name Dilantin); Hydrocortisone; Placebo
Intervention description: Three days prior to imaging, participants will take two capsules containing phenytoin tablets (100 mg) by mouth at 0900 hours and 2100 hours (400 mg/day) for a total of three days with the last dose at 0900 hours on the day of the imaging (7 doses total).; Beginning two days prior to the imaging (the day after initiating the phenytoin or placebo), participants will begin taking 4 tablets containing hydrocortisone (20 mg) or placebo also at 0900 hours and 2100 hours (160 mg/day) with the last dose at 0900 hours on the day of the imaging (5 doses total). The doses were selected to achieve a low therapeutic blood level of phenytoin and stress level of cortisol. Newcomer et al. (1999) used this dose of hydrocortisone in healthy controls. The imaging will be performed at approximately 1300 hours.; Participants take two capsules of placebo 100 mg at 0900 hours and 2100 hours for a total of 3 days with the last dose at 0900 hours on the day of imaging (7 doses total). Beginning two days prior to the imaging (the day after initiating placebo), participants will being taking 4 tablets containing placebo (20 mg) also at 0900 hours and 2100 hours with the last dose at 0900 hours on the day of the imaging (5 doses total).
Intervention MeSH terms: Hydrocortisone; Phenytoin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: Double (Participant, Investigator)
Enrollment: 17.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Phenytoin; Dilantin; Corticosteroid; Neuroprotection; Mania; Cognition; Mood; Memory; Hydrocortisone; Healthy Controls; MRI; hippocampal activation

Summary:

      The purpose of this research is to determine if patients who receive phenytoin (also commonly
      known as Dilantin) before taking corticosteroids will show less memory impairment and
      hypomanic symptoms (feelings of agitation, overexcitement or hyperactivity) than those
      receiving placebo (an inactive substance). This research also seeks to determine if patients
      taking phenytoin before corticosteroids show more activity in the area of the brain involved
      with memory than those receiving placebo.

      This research is being done because increased levels of cortisol (the body's natural
      corticosteroid) in the body are frequently associated with forgetfulness, and interventions
      that may prevent or reverse this effect are of great importance.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Age 18-50 years

          -  Men or women

          -  Vision corrected to at least 20-40

          -  No tobacco use

          -  Education of ≥12 years (No GED)

        Exclusion Criteria:

          -  History of major psychiatric illness defined as major depressive disorder, bipolar
             disorder, post traumatic stress disorder, panic disorder, schizoaffective disorder,
             schizophrenia or eating disorders

          -  History of drug or alcohol abuse or dependence

          -  History of neurological disorders including seizures, brain surgery, multiple
             sclerosis, Parkinson's disease

          -  Taking central nervous system (CNS) acting medications (e.g. antidepressants,
             hypnotics)

          -  History of allergic reaction or medical contraindication to phenytoin or
             hydrocortisone therapy

          -  Metal implants, claustrophobia or other contraindications to MRI

          -  Significant medical conditions (e.g. myocardial infarction, diabetes)

          -  Pregnant or nursing women

          -  Prisoners

          -  History of mental retardation, special education classes, dementia or other severe
             cognitive disorders

          -  Baseline Hamilton Rating Scale for Depression Score > 7

          -  History of a suicide attempt

          -  History of systemic corticosteroid use or current inhaled corticosteroid use