Efficacy of Pharmacological Treatment of Working Memory Impairment After Traumatic Brain Injury: Evaluation With fMRI

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00489892
Recruitment Status : Unknown
Verified July 2007 by Kessler Foundation.
Recruitment status was:  Recruiting
First Posted : June 21, 2007
Last Update Posted : July 25, 2007
University of Medicine and Dentistry of New Jersey
Information provided by:
Kessler Foundation

Brief Summary:

This study is designed to examine the effects of a wake-promoting agent (Modafinil) on working memory (WM) in persons with moderate to severe TBI utilizing a double blinded placebo controlled methodology. Our approach is to evaluate participants with BOLD fMRI and a limited neuropsychological battery to examine WM performance before and after pharmacological intervention.


  1. Because increased cognitive effort (as a function of decreased efficiency after TBI) is presumed to underlie fMRI activation dispersion that is seen during central executive WM tasks, we anticipate an attenuation of cerebral activation in prefrontal cortex during pharmacological intervention with Modafinil when compared to placebo administration on the mPASAT and vigilance testing.
  2. There will be a correlation between the decreased dispersion of the fMRI signal on scans and improvement in neuropsychological measures when individuals are on Modafinil that is not seen when they are taking placebo.

Condition or disease Intervention/treatment Phase
Traumatic Brain Injury Severe Traumatic Brain Injury Drug: Modafinil Not Applicable

Detailed Description:

Work from our institution has shown that moderate and severe TBI subjects demonstrate an altered cerebral representation when they attempt to process a verbal WM task. Specifically, our data show a post-TBI pattern of activation that is dispersed and more lateralized to the right hemisphere, as compared to healthy controls. Taken together, we interpret these findings to mean that it is requires more cerebral resources for TBI subjects to process tasks that were previously more automatic. In other words, their processing is less efficient. This is consistent with TBI patients’ self-reports of needing to expend greater cognitive effort to perform such tasks, both in the lab and in everyday life. Our preliminary data was the first step in understanding the cerebral substrate of these difficulties. However, simply indicating that individuals with TBI have a WM problem is not enough. The development of targeted interventions to ameliorate these deficits is the next step in the treatment process.

The present proposal has important implications for TBI rehabilitation. One of the major goals of cognitive remediation is to help TBI patients learn new information more accurately and efficiently, and to improve their performance in activities of everyday life. 123 Because WM impairments are so prevalent in TBI, the present study can help to shed light on potential treatment alternatives for these potentially devastating problems. In spite of the prevalence and popularity of cognitive remediation strategies and procedures, there remains little empirical support for their efficacy, and virtually no understanding of the underlying neurocognitive processes that facilitate intervention. The ability to develop a potentially efficacious treatment modality, which has a solid foundation, would be immensely beneficial.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double
Primary Purpose: Treatment
Official Title: Efficacy of Pharmacological Treatment of Working Memory Impairment After Traumatic Brain Injury: Evaluation With fMRI
Study Start Date : August 2003
Estimated Study Completion Date : December 2008

Resource links provided by the National Library of Medicine

Primary Outcome Measures :
  1. mPASAT [ Time Frame: Pre-Treatment, Post-Treatment ]
  2. Dispersion of fMRI signal [ Time Frame: Pre-Treatment, Post-Treatment ]
  3. Simple Vigilance Task [ Time Frame: Pre-Treatment, Post-Treatment ]
  4. Neuropsychological Battery (Digit Vigilance Task, California Verbal Learning Test, Digit Span and Continuous Performance Task) [ Time Frame: Pre-Treatment, Post-Treatment ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 45 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

We will include only those subjects who have sustained moderate to severe initial injuries, as defined by an initial 24-hour Glasgow Coma Scale 128 scores below 13. In the event that a GCS score is not available, subjects will only be included if there is sufficient medical documentation that would allow for a post-hoc estimation of initial GCS, or if other confirmatory data (e.g., positive anatomic neuroimaging findings, focal neurologic signs) are available. Individuals with a history of prior moderate to severe head injury, stroke, seizures, severe psychiatric disturbances (i.e., those known to influence memory performance, such as schizophrenia, bipolar disorder), or drug abuse will not be included as subjects. In addition, a score of 11 or greater on the Mini Mental Status Exam will be required to insure that subject can participate effectively in the study protocol. Because of potential effects on cognition and hemodynamic response, subjects currently taking benzodiazepines, narcotics, neuroleptics, anticonvulsants, antispasticity agents or psychostimulants will not be included.

In addition, any patient that is on medications that may interact with any of the study medications (e.g. birth control bills or cyclosporin). Psychiatric symptoms and substance abuse history will be obtained using a structured psychiatric interview, the Diagnostic Interview Schedule 129DIS. In addition patients with history of drug dependency, hypertension out of control, significant cardiac disease, or inability to undergo MRI. (e.g. metalworker, Medtronic infusion pump)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00489892

Contact: Elie P Elovic, M.D. (973) 243-6815

United States, New Jersey
Kessler Medical Rehabilitation Research & Education Corporation Recruiting
West Orange, New Jersey, United States, 07052
Principal Investigator: Elie P Elovic, M.D.         
Sub-Investigator: Glenn Wylie, Ph.D         
Sub-Investigator: John DeLuca, Ph.D.         
Sponsors and Collaborators
Kessler Foundation
University of Medicine and Dentistry of New Jersey
Principal Investigator: Elie P Elovic, M.D. Kessler Medical Rehabilitation Research & Education Corporation

Publications: Identifier: NCT00489892     History of Changes
Other Study ID Numbers: D-437-02
First Posted: June 21, 2007    Key Record Dates
Last Update Posted: July 25, 2007
Last Verified: July 2007

Keywords provided by Kessler Foundation:
traumatic brain injury
working memory

Additional relevant MeSH terms:
Wounds and Injuries
Brain Injuries
Brain Injuries, Traumatic
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Craniocerebral Trauma
Trauma, Nervous System
Wakefulness-Promoting Agents
Central Nervous System Stimulants
Cytochrome P-450 CYP3A Inducers
Cytochrome P-450 Enzyme Inducers
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs