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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified July 2007 by Kessler Foundation.
Recruitment status was  Recruiting
Sponsor:
Collaborators:
University of Medicine and Dentistry of New Jersey
Cephalon
Information provided by:
Kessler Foundation
ClinicalTrials.gov Identifier:
NCT00489892
First received: June 20, 2007
Last updated: July 23, 2007
Last verified: July 2007
  Purpose

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.

Hypotheses

  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 Intervention
Traumatic Brain Injury
Severe Traumatic Brain Injury
Drug: Modafinil

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Efficacy of Pharmacological Treatment of Working Memory Impairment After Traumatic Brain Injury: Evaluation With fMRI

Resource links provided by NLM:


Further study details as provided by Kessler Foundation:

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

Estimated Enrollment: 20
Study Start Date: August 2003
Estimated Study Completion Date: December 2008
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.

  Eligibility

Ages Eligible for Study:   18 Years to 45 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00489892

Contacts
Contact: Elie P Elovic, M.D. (973) 243-6815 eelovic@kmrrec.org

Locations
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
Cephalon
Investigators
Principal Investigator: Elie P Elovic, M.D. Kessler Medical Rehabilitation Research & Education Corporation
  More Information

Publications:

ClinicalTrials.gov Identifier: NCT00489892     History of Changes
Other Study ID Numbers: D-437-02, 0120020166, M-166-2002
Study First Received: June 20, 2007
Last Updated: July 23, 2007
Health Authority: United States: Food and Drug Administration
United States: Institutional Review Board

Keywords provided by Kessler Foundation:
traumatic brain injury
TBI
working memory
modafinil
fMRI
MRI

Additional relevant MeSH terms:
Brain Injuries
Brain Diseases
Central Nervous System Diseases
Craniocerebral Trauma
Nervous System Diseases
Trauma, Nervous System
Wounds and Injuries
Modafinil
Central Nervous System Agents
Central Nervous System Stimulants
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses
Wakefulness-Promoting Agents

ClinicalTrials.gov processed this record on October 23, 2014