Phenytoin for Memory Impairment Secondary to Megestrol

NCT02595723 | Completed Phase 4 Results

• 1 other identifier: 032015-004
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Cognitive Impairment

Outcome Measures

Primary Outcomes (1)

• Rey Auditory Verbal Learning Test (RAVLT)

  Rey Auditory Verbal Learning Test (RAVLT) is a test of verbal learning and declarative memory. During the test, 15 nouns that are read aloud for 5 consecutive trials. Each trial is followed by a free recall test (participant is asked to recall the words that were just read to them). The sum of correctly recalled words across 5 trials is called the total raw score. The raw scores on the total recall (number of words correct across trials 1-5) are converted to standardized T-scores (Mean=50; SD=10; range 20-100) based on participant age and gender. The scores below are presented as T-scores, with higher scores indicative of better performance.

  4 days after intervention administration

Study Arms (3)

Phenytoin, Then Megestrol

EXPERIMENTAL

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.

Drug: Phenytoin 200 mg capsule; Drug: Megestrol 800 mg liquid

Placebo, Then Megestrol

EXPERIMENTAL

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.

Drug: Megestrol 800 mg liquid; Drug: Phenytoin-matched Placebo capsule

Placebo, Then Placebo

EXPERIMENTAL

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.

Drug: Phenytoin-matched Placebo capsule; Drug: Megestrol-matched liquid Placebo

Interventions

Phenytoin 200 mg capsule DRUG

Phenytoin oral capsule was initiated on Day 1 and administered at 200 mg twice/day for four consecutive days (Days 1 - 4).

Phenytoin, Then Megestrol

Megestrol 800 mg liquid DRUG

Liquid megestrol 800 mg/was initiated on Day 2 and administered at 09:00 for three consecutive days (Days 2 - 4).

Phenytoin, Then Megestrol; Placebo, Then Megestrol

Phenytoin-matched Placebo capsule DRUG

Phenytoin-matched oral Placebo capsule was initiated on Day 1 and administered for four consecutive days (Days 1 - 4).

Placebo, Then Megestrol; Placebo, Then Placebo

Megestrol-matched liquid Placebo DRUG

Megestrol-matched liquid placebo was initiated on Day 2 and administered at 09:00 for three consecutive days (Days 2 - 4).

Placebo, Then Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Texas Southwestern Medical Center: lead
• The Rogosin Institute: collaborator

Study Sites (1)

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

MeSH Terms

Conditions

Cognitive Dysfunction

Interventions

Phenytoin; Megestrol; Fluid Therapy

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Hydantoins; Imidazolidines; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Drug Therapy; Therapeutics

Results Point of Contact

• Title: E. Sherwood Brown, M.D., Ph.D.
• Organization: UT Southwestern Medical Center

sherwood.brown@utsouthwestern.edu

214-645-6950

Study Officials

• E. Sherwood Brown, MD, PhD

  University of Texas Southwestern Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Each participant receives three treatments: phenytoin + megestrol, placebo + megestrol, or placebo + placebo

Study Record Dates

• First Submitted: July 2, 2015
• First Posted: November 3, 2015
• Study Start: July 1, 2015
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2016
• Last Updated: September 9, 2019
• Results First Posted: September 9, 2019

Record last verified: 2019-09

Locations

US (1)