Phenytoin for Memory Impairment Secondary to Megestrol
Condition: Cognitive Impairment
MeSH terms: Cognitive Dysfunction
Intervention: Phenytoin 200 mg capsule; Megestrol 800 mg liquid; Phenytoin-matched Placebo capsule; Megestrol-matched liquid Placebo
Intervention description: Phenytoin oral capsule was initiated on Day 1 and administered at 200 mg twice/day for four consecutive days (Days 1 - 4).; Liquid megestrol 800 mg/was initiated on Day 2 and administered at 09:00 for three consecutive days (Days 2 - 4).; Phenytoin-matched oral Placebo capsule was initiated on Day 1 and administered for four consecutive days (Days 1 - 4).; Megestrol-matched liquid placebo was initiated on Day 2 and administered at 09:00 for three consecutive days (Days 2 - 4).
Intervention MeSH terms: Megestrol; Megestrol Acetate; Phenytoin
Phase: Phase 4
Study type: Interventional
Primary purpose: Other
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Each participant receives three treatments: phenytoin + megestrol, placebo + megestrol, or placebo + placebo
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 21.0
Sex: All
Minimum age: 18 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers

Summary:

      This study is designed to test if megestrol acetate induces changes in declarative memory in
      healthy controls and if pre-administration of phenytoin can ameliorate any induced cognitive
      impairments.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Healthy men and women age 18-50 years

          -  Education of ≥ 12 years and baseline Rey Auditory Verbal Learning Test (RAVLT) total
             words recalled score ≥ 40 (normal baseline memory)

          -  Body mass index (BMI) between 18.5-35

          -  The ability to read and speak English as not all neurocognitive assessments have been
             translated and validated in other languages.

        Exclusion Criteria:

          -  History (lifetime) of Bipolar Disorder, Major Depressive Disorder, psychotic
             depressive, schizophrenic, schizoaffective, or other Axis I psychotic disorders

          -  Has an unstable general medical condition (GMC) or significant medical condition,
             including but not limited to myocardial infarction, cancer, diabetes (hypertension is
             allowed if condition is being treated and is stable)

          -  Vulnerable populations including pregnant or nursing women, the incarcerated, or those
             with severe cognitive disorders

          -  Education history that includes Special Education or history of mental disability

          -  History of psychotropic medication therapy in the past 30 days

          -  Baseline Quick Inventory of Depressive Symptoms-Clinician Rated (QIDS-C) > 5

          -  Initiation of new medications within 14 days of the baseline visit, with the exception
             of over-the-counter (OTC) as needed medications (e.g. Tylenol, Advil, Motrin, etc.)

          -  Significant hypertensive blood pressure at baseline, defined as either systolic
             pressure > 150 or diastolic pressure > 95

          -  Febrile at baseline, defined as body temperature ≥ 100.5°F (38°C)

          -  Baseline heart rate > 100 bpm or < 50 bpm

          -  Medical history of diseases with central nervous system (CNS)-involvement, including
             but not limited to stroke, traumatic brain injury, and loss of consciousness > 1
             minute

          -  History of allergic reaction or medical contraindication to megestrol or phenytoin

          -  Clinically significant abnormalities on baseline labs (e.g. hypokalemia,
             hypernatremia, anemia)

          -  Lifetime history of an immunosuppressive disorder or immunosuppressive therapy with
             within the past 6 months

          -  History of blood clots such as myocardial infarction (MI), stroke, deep vein
             thromboses (DVTs), pulmonary embolism (PE) or blood clotting disorder

          -  Currently actively suicidal or considered a high suicide risk (e.g. more than one
             lifetime suicide attempt or any attempt in the past 12 months)

          -  Any reason not listed which, as determined by the principle investigator (PI), would
             affect participant safety in the study