Traumatic Brain InjuryNCT00489892
Efficacy of Pharmacological Treatment of Working Memory Impairment After Traumatic Brain Injury: Evaluation With fMRI
A study testing Modafinil in people with Traumatic Brain Injury and Severe Traumatic Brain Injury, run by Kessler Foundation at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 45 years
- Conditions the study is for
- Traumatic Brain Injury, Severe Traumatic Brain Injury
- What is being tested?
- Modafinil
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2003to Dec 2008
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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)
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site, 1 recruiting
- Recruiting
Kessler Medical Rehabilitation Research & Education Corporation
West Orange, New Jersey, 07052
Elie P Elovic, M.D.
Glenn Wylie, Ph.D
About this study
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
- 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.
- 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.
Read the 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.
- Being tested
- Modafinil
- Keywords
- traumatic brain injury, TBI, working memory, modafinil, fMRI, MRI
- Medical subject headings
- Brain Injuries, Traumatic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ModafinilDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
mPASAT
Measured: Pre-Treatment, Post-Treatment
Dispersion of fMRI signal
Measured: Pre-Treatment, Post-Treatment
Simple Vigilance Task
Measured: Pre-Treatment, Post-Treatment
Neuropsychological Battery (Digit Vigilance Task, California Verbal Learning Test, Digit Span and Continuous Performance Task)
Measured: Pre-Treatment, Post-Treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jun 2007 (estimated)
- Study startAug 2003
- Study completionDec 2008 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (10)Papers the sponsor has linked to this study.
- Other trials for Traumatic Brain InjuryStudies of the same condition, open and under way.
- More trials run by Kessler FoundationThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Enrolment
- 20 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Kessler Foundation
- Sponsor type
- University, hospital or other
- Collaborators
- University of Medicine and Dentistry of New Jersey, Cephalon
- Investigators
- Elie P Elovic, M.D., Principal investigator, Kessler Medical Rehabilitation Research & Education Corporation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00489892
- Sponsor's protocol ID
- D-437-02
- Other IDs
- 0120020166, M-166-2002
- Status last verified
- Jul 2007
- First submitted
- 20 Jun 2007
- Last updated
- 25 Jul 2007
- Results posted
- No
- Data monitoring committee
- No
Publications
Baddeley A. Working memory. Science. 1992 Jan 31;255(5044):556-9. doi: 10.1126/science.1736359.
PubMed 1736359Levin 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.
PubMed 2213159McDowell 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.
PubMed 9347480Ponsford J, Kinsella G. Attentional deficits following closed-head injury. J Clin Exp Neuropsychol. 1992 Sep;14(5):822-38. doi: 10.1080/01688639208402865.
PubMed 1474148Stuss 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.
PubMed 4022286McAllister 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.
PubMed 10522888Thurman 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.
PubMed 10671706Schootman M, Fuortes LJ. Ambulatory care for traumatic brain injuries in the US, 1995-1997. Brain Inj. 2000 Apr;14(4):373-81. doi: 10.1080/026990500120664.
PubMed 10815845Guerrero 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.
PubMed 10695573Smith 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.
PubMed 8670634
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2007. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy of Pharmacological Treatment of Working Memory Impairment After Traumatic Brain Injury: Evaluation With fMRI
- ClinicalTrials.gov ID
- NCT00489892
- Acronym / sponsor ID
- D-437-02
- Keywords
- traumatic brain injury, TBI, working memory, modafinil, fMRI, MRI
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 20 participants (estimated)
- Lead sponsor
- Kessler FoundationUniversity, hospital or other
- Collaborators
- University of Medicine and Dentistry of New Jersey, Cephalon
- Study start
- Aug 2003
- Study completion
- Dec 2008 (estimated)
- First posted
- 21 Jun 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
- 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.
- 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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
Who may qualify
- Ages
- 18 to 45 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- 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)
Key exclusion criteria (0 listed)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Modafinil | Drug | – |
Primary outcome
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2007.
- Background: PubMed 1736359Baddeley A. Working memory. Science. 1992 Jan 31;255(5044):556-9. doi: 10.1126/science.1736359.
- Background: PubMed 2213159Levin 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.
- Background: PubMed 9347480McDowell 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.
- Background: PubMed 1474148Ponsford J, Kinsella G. Attentional deficits following closed-head injury. J Clin Exp Neuropsychol. 1992 Sep;14(5):822-38. doi: 10.1080/01688639208402865.
- Background: PubMed 4022286Stuss 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.
- Background: PubMed 10522888McAllister 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.
- Background: PubMed 10671706Thurman 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.
- Background: PubMed 10815845Schootman M, Fuortes LJ. Ambulatory care for traumatic brain injuries in the US, 1995-1997. Brain Inj. 2000 Apr;14(4):373-81. doi: 10.1080/026990500120664.
- Background: PubMed 10695573Guerrero 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.
- Background: PubMed 8670634Smith 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Elie P Elovic, M.D. principal investigator
Kessler Medical Rehabilitation Research & Education Corporation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Modafinil in people with Traumatic Brain Injury and Severe Traumatic Brain Injury, run by Kessler Foundation at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Jul 2007. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Elie P Elovic, M.D. ((973) 243-6815, eelovic@kmrrec.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
mPASAT (time frame: Pre-Treatment, Post-Treatment). The study lists 4 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00489892, which also lists 10 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2007.