Phenytoin for Memory Impairment Secondary to Megestrol
Condition: Cognitive Impairment
MeSH terms: Cognitive Dysfunction
Study type: Interventional
Phase: Phase 4

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.
    

Detailed description: 
      Healthy adults (n=20) will be recruited and informed consent will be obtained. Participants
      will agree to a number of visits, a Baseline Visit, 6 Study Visits, and a follow-up Safety
      Visit. Each course of study drug will be followed by a washout, but allowed preexisting
      medications will not be stopped for study participation. A small subset (n=4) of participants
      will also undergo MRI scanning as a component of their visits following drug administration.

      Baseline Visit: Cognition will be assessed by a variety of measures, which will determine
      baseline declarative memory and working memory. Mood will be assessed by a psychiatric
      interview, self-assessments, and a review of any standing physical symptoms will be completed
      for comparison to any side effects which develop after medication administration. Vital signs
      will be recorded and women will be screened for pregnancy. Blood will be collected for
      complete blood count (CBC) and comprehensive metabolic panel (CMP).

      Visit 1: Participants will be randomized to one of three treatment possibilities: 1)
      phenytoin with megestrol, 2) placebo with megestrol, 3) placebo with placebo. Participants
      will receive phenytoin (200 mg BID) or placebo and will be instructed to take this medication
      for one full day (two doses) before starting their megestrol. They will take this medication
      for a total of 3.5 days.

      Visit 2: After the participants have completed their medication course on the morning of this
      visit day, they will return to have cognition and mood reassessed. Vital signs will be taken
      and blood will be drawn to assess CMP, CBC, cortisol and phenytoin levels. Participants will
      now enter a "washout" period of this medicine combination (approximately 3 weeks) before
      returning for their next visit. For those participants offered the MRI scans, their visit
      will extend to approximately 3 hours.

      Visit 3: Participants will return and be randomized to one of remaining two treatment
      possibilities as detailed above. Participants will again be instructed to start the first
      medication and take for one full day before taking the second medication, and will be
      instructed to take their second medication at starting the following day after starting the
      first medication at 0900 hours and continue taking the drugs for 3 consecutive days.

      Visit 4: After the participants have completed their medication course on the morning of this
      visit day, they will return to have cognition and mood reassessed; completing all previously
      administered assessments excepting the Structured Clinical Interview for the Diagnostic and
      Statistical Manual of Mental Disorders (SCID). Vital signs will be taken and blood will be
      drawn to assess CMP, CBC, cortisol and phenytoin levels. Participants will now enter a
      "washout" period of this medicine combination (approximately 3 weeks) before returning for
      their next visit. For those participants offered the MRI scans, their visit will extend to
      approximately 3 hours.

      Visit 5: Participants will return and receive the remaining treatment possibility, detailed
      above. Participants will again be instructed to start the first medication and take for one
      full day before taking the second medication and will be instructed to take their second
      medication at starting the following day after starting the first medication at 0900 hours
      and continue taking the drugs for 3 consecutive days.

      Visit 6: After the participants have completed their medication course on the morning of this
      visit day, they will return to have cognition and mood reassessed. Vital signs will be taken
      and blood will be drawn to assess CMP, CBC, cortisol and phenytoin levels. Participants will
      now enter a "washout" period of this medicine combination (approximately 3 weeks) before
      returning for their final visit. For those participants offered the MRI scans, their visit
      will extend to approximately 3 hours.

      Safety Visit: Participants will return for a final "safety" visit which will evaluate any
      remaining side effects, take vital signs, and include a final urinary pregnancy test (for
      women).
    

Intervention name(s): Phenytoin 200 mg capsule; Megestrol 800 mg liquid; Phenytoin-matched Placebo capsule; Megestrol-matched liquid Placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 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
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)
Primary purpose: Other