Phenytoin as a Neuroprotective Agent Against Corticosteroid-induced Functional Imaging Changes - Full Text View

Sponsor:	University of Texas Southwestern Medical Center
Information provided by:	University of Texas Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT00591006

Purpose

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.

Condition	Intervention	Phase
Healthy	Drug: Phenytoin, Dilantin	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Factorial Assignment Masking: Double Blind (Subject, Investigator) Primary Purpose: Treatment
Official Title:	Phenytoin as a Neuroprotective Agent Against Corticosteroid-induced Functional Imaging Changes

Resource links provided by NLM:

MedlinePlus related topics: Memory

Drug Information available for: Hydrocortisone acetate Hydrocortisone Phenytoin Proctofoam-HC Hydrocortisone hemisuccinate Hydrocortamate Hydrocortisone 21-sodium succinate Hydrocortisone cypionate Phenytoin sodium Cortisol succinate Cortisol 21-phosphate Corticosteroids

U.S. FDA Resources

Further study details as provided by University of Texas Southwestern Medical Center:

Primary Outcome Measures:

Scored Memory and Mood Assessments specified; fMRI Neuroimaging data obtained through Novelty Detection Tasks; Structural MRI and MRS measuring Hippocampal volume and activation [ Time Frame: 3 days after introduction to Phenytoin/Hydrocortisone or Placebo ] [ Designated as safety issue: No ]

Estimated Enrollment:	16
Study Start Date:	January 2008
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Placebo, Placebo	Drug: Phenytoin, Dilantin participants will take two capsules containing phenytoin tablets (100 mg) or identical placebo 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 imaging will be performed at 1300 hours. Other Names: 5,5-Diphenylhydantoin Fenitoin Antisacer Difenin Dihydan Dilantin Diphenylhydantoin Epamin Hydantol Sodium Diphenylhydantoinate
Experimental: 2 Phenytoin, Placebo	Drug: Phenytoin, Dilantin participants will take two capsules containing phenytoin tablets (100 mg) or identical placebo 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 imaging will be performed at 1300 hours. Other Names: 5,5-Diphenylhydantoin Fenitoin Antisacer Difenin Dihydan Dilantin Diphenylhydantoin Epamin Hydantol Sodium Diphenylhydantoinate
Experimental: 3 Hydrocortisone, Placebo	Drug: Phenytoin, Dilantin participants will take two capsules containing phenytoin tablets (100 mg) or identical placebo 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 imaging will be performed at 1300 hours. Other Names: 5,5-Diphenylhydantoin Fenitoin Antisacer Difenin Dihydan Dilantin Diphenylhydantoin Epamin Hydantol Sodium Diphenylhydantoinate
Experimental: 4 Hydrocortisone, Phenytoin	Drug: Phenytoin, Dilantin participants will take two capsules containing phenytoin tablets (100 mg) or identical placebo 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 imaging will be performed at 1300 hours. Other Names: 5,5-Diphenylhydantoin Fenitoin Antisacer Difenin Dihydan Dilantin Diphenylhydantoin Epamin Hydantol Sodium Diphenylhydantoinate

Show Detailed Description

Eligibility

Ages Eligible for Study:	18 Years to 50 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	Yes

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 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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00591006

Locations

United States, Texas
UT Southwestern Medical Center of Dallas/Parkland Memorial Hospital
Dallas, Texas, United States, 75390-8849

Sponsors and Collaborators

University of Texas Southwestern Medical Center

Investigators

Principal Investigator:

Sherwood Brown, M.D.,Ph.D.

UT Southwestern Medical Center of Dallas

More Information

Additional Information:

Psychoneuroendocrine Research Group Website This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Dr. Sherwood Brown, PhD. MD. Assistant Professor and Program Director, UT Southwestern Medical Center
ClinicalTrials.gov Identifier:	NCT00591006 History of Changes
Other Study ID Numbers:	1R21MH078182, 1R21MH078182
Study First Received:	December 27, 2007
Last Updated:	August 2, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by University of Texas Southwestern Medical Center:

Phenytoin
Dilantin
Corticosteroid
Neuroprotection
Mania
Cognition
Mood

Memory
Hydrocortisone
Healthy Controls
MRI
Determine the effect of hydrocortisone on hippocampal activation during a task.
Determine the effect of phenytoin on hippocampal activation during a task.
Determine if phenytoin given prior to hydrocortisone will prevent changes in hippocampal activation on fMRI.

Additional relevant MeSH terms:

Phenytoin
Cortisol succinate
Hydrocortisone acetate
Hydrocortisone
Neuroprotective Agents
Anticonvulsants

Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Anti-Inflammatory Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on February 12, 2012