Clinical trial NCT02595723
Conditions: Cognitive Impairment
Sponsor: University of Texas Southwestern Medical Center
Start date: 2015-07-01; Completion date: 2016-12-01
Enrollment: 21 participants; Allocation: RANDOMIZED; Intervention model: CROSSOVER

Brief 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).

Arms: arm 1: Participants first received pretreatment with Phenytoin 200 mg capsule twice/day for one day. Participants then received both Phenytoin (200 mg capsule twice/day) and liquid Megestrol (800 mg/day) for three consecutive days. arm 2: Participants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Megestrol (800 mg/day) for three consecutive days. arm 3: Participants first received pretreatment with Placebo (matching Phenytoin 200 mg capsule) twice/day for one day. Participants then received both Placebo (matching Phenytoin 200 mg capsule) twice/day and liquid Placebo (matching liquid Megestrol 800 mg/day) for three consecutive days.
Interventions: intervention 1: Phenytoin 200 mg capsule intervention 2: Megestrol 800 mg liquid intervention 3: Phenytoin-matched Placebo capsule intervention 4: Megestrol-matched liquid Placebo
Intervention descriptions: intervention 1: Phenytoin oral capsule was initiated on Day 1 and administered at 200 mg twice/day for four consecutive days (Days 1 - 4). intervention 2: Liquid megestrol 800 mg/was initiated on Day 2 and administered at 09:00 for three consecutive days (Days 2 - 4). intervention 3: Phenytoin-matched oral Placebo capsule was initiated on Day 1 and administered for four consecutive days (Days 1 - 4). intervention 4: Megestrol-matched liquid placebo was initiated on Day 2 and administered at 09:00 for three consecutive days (Days 2 - 4).

Protocol documents: