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

NCT00489892 | Unknown

• 3 other identifiers: D-437-020120020166M-166-2002
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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. Hypotheses

1. 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. 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.

Conditions

Traumatic Brain Injury; Severe Traumatic Brain Injury

Keywords

traumatic brain injury; TBI; working memory; modafinil; fMRI; MRI

Outcome Measures

Primary Outcomes (4)

• mPASAT

  Pre-Treatment, Post-Treatment

• Dispersion of fMRI signal

  Pre-Treatment, Post-Treatment

• Simple Vigilance Task

  Pre-Treatment, Post-Treatment

• Neuropsychological Battery (Digit Vigilance Task, California Verbal Learning Test, Digit Span and Continuous Performance Task)

  Pre-Treatment, Post-Treatment

Interventions

Modafinil DRUG

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

Sponsors & Collaborators

• Kessler Foundation: lead
• University of Medicine and Dentistry of New Jersey: collaborator
• Cephalon: collaborator

Study Sites (1)

Kessler Medical Rehabilitation Research & Education Corporation

West Orange, New Jersey, 07052, United States

RECRUITING

Related Publications (10)

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  PMID: 1736359 BACKGROUND

• Levin HS, Gary HE Jr, Eisenberg HM, Ruff RM, Barth JT, Kreutzer J, High WM Jr, Portman S, Foulkes MA, Jane JA, et al. Neurobehavioral outcome 1 year after severe head injury. Experience of the Traumatic Coma Data Bank. J Neurosurg. 1990 Nov;73(5):699-709. doi: 10.3171/jns.1990.73.5.0699.

  PMID: 2213159 BACKGROUND

• McDowell S, Whyte J, D'Esposito M. Working memory impairments in traumatic brain injury: evidence from a dual-task paradigm. Neuropsychologia. 1997 Oct;35(10):1341-53. doi: 10.1016/s0028-3932(97)00082-1.

  PMID: 9347480 BACKGROUND

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  PMID: 1474148 BACKGROUND

• Stuss DT, Ely P, Hugenholtz H, Richard MT, LaRochelle S, Poirier CA, Bell I. Subtle neuropsychological deficits in patients with good recovery after closed head injury. Neurosurgery. 1985 Jul;17(1):41-7. doi: 10.1227/00006123-198507000-00007.

  PMID: 4022286 BACKGROUND

• McAllister TW, Saykin AJ, Flashman LA, Sparling MB, Johnson SC, Guerin SJ, Mamourian AC, Weaver JB, Yanofsky N. Brain activation during working memory 1 month after mild traumatic brain injury: a functional MRI study. Neurology. 1999 Oct 12;53(6):1300-8. doi: 10.1212/wnl.53.6.1300.

  PMID: 10522888 BACKGROUND

• Thurman DJ, Alverson C, Dunn KA, Guerrero J, Sniezek JE. Traumatic brain injury in the United States: A public health perspective. J Head Trauma Rehabil. 1999 Dec;14(6):602-15. doi: 10.1097/00001199-199912000-00009.

  PMID: 10671706 BACKGROUND

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  PMID: 10815845 BACKGROUND

• Guerrero JL, Thurman DJ, Sniezek JE. Emergency department visits associated with traumatic brain injury: United States, 1995-1996. Brain Inj. 2000 Feb;14(2):181-6.

  PMID: 10695573 BACKGROUND

• Smith EE, Jonides J, Koeppe RA. Dissociating verbal and spatial working memory using PET. Cereb Cortex. 1996 Jan-Feb;6(1):11-20. doi: 10.1093/cercor/6.1.11.

  PMID: 8670634 BACKGROUND

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Modafinil

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Study Officials

• Elie P Elovic, M.D.

  Kessler Medical Rehabilitation Research & Education Corporation

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Elie P Elovic, M.D.

CONTACT

(973) 243-6815; eelovic@kmrrec.org

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: June 20, 2007
• First Posted: June 21, 2007
• Study Start: August 1, 2003
• Study Completion: December 1, 2008
• Last Updated: July 25, 2007

Record last verified: 2007-07

Locations

US (1)