Effect of Namenda on Short Term Memory and Attention in Patients With Mild to Moderate Traumatic Brain Injury
The purpose of this study is to determine whether memantine (Namenda) improves memory and attention in patients with mild to moderate traumatic brain injury.
Background and significance:
Each year in the United States approximately 1.5 million people sustain a traumatic brain injury (TBI) and of these approximately 80-90,000 result in long-term or lifelong disability. An estimated 5.3 million people are currently living with a disability due to TBI. The CDC estimated that about 75% (1.1 million) of the reported TBIs are concussions or other forms of mild TBIs (MTBI). However, the incidence of MTBI has been vastly underestimated according to a CDC Report to Congress.
The long term problem associated with MTBI is primarily memory impairment. Memory impairment resulting form MTBI is not likely to improve with time beyond the initial stabilizing period of about one year post-injury. Dementia from Alzheimer's Disease produces cognitive problems that are similar to those experienced by patients with mild to moderate traumatic brain injury. The efficacy of Namenda for treatment of cognitive problems due to Alzheimer's Dementia suggests it may have efficacy for treatment of short term memory and attention deficits in patients with mild to moderate traumatic brain injury.
Overall Design and Plan of Study:
Twenty post-TBI patients whose TBI occurred at least 1 year prior to beginning the study will be recruited for this pilot study. Patients who meet screening criteria will have cognitive abilities assessed at baseline and at subsequent visits while taking Namenda or placebo. Patients will be randomly assigned to begin either Namenda or placebo and will then crossover to the alternate treatment. Each patient will participate in the study for a total of 32 to 34 weeks. Patients completing the study will have 10 total visits and 6 visits at which a cognitive test battery will be administered. This will include 24 weeks of study drug treatment (12 weeks of Namenda and 12 weeks of placebo) and two 4-week washout periods. Patients will be titrated up to 20 mg of Namenda per day. Namenda and placebo will be provided by Forest Laboratories Inc.
Cognitive screening criteria include a Galveston Orientation and Amnesia Test (GOAT) score of at least 75, and either a Mini-Mental State Exam (MMSE) score of 20 to 27 obtained at the screening visit, or a California Verbal Learning Test (CVLT) total score for trials 1-5 one standard deviation lower than the age matched normative score. The CVLT score for inclusion may be obtained from the medical record provided that the CVLT testing occurred one year or more post TBI and within two years of study entry.
The cognitive test battery measurements will be made at the first baseline before Namenda or placebo administration (week 0), and at weeks 6, & 12 after Namenda or placebo administration. After washout for 4 weeks, the second baseline (week 16) will be assessed, and the cognitive test battery will be administered again at weeks 22 & 28 after Namenda or placebo administration.
The cognitive test battery used to assess efficacy will utilize the following tests;
Verbal Memory: Hopkins Verbal Learning Test Revised (HVLT-R). Visual Memory: Brief Visuo-Spatial Memory Test Revised (BVMT-R). Speed of processing: Trail Making Test Part A. Attention: Trail Making Test Part B. Memory/processing speed: Symbol Digit Modality Test (SDMT).
The primary endpoints for cognitive assessment will be the HVLT-R and the BVMT-R. The 6 different forms of the HVLT-R and BVMT-R will be administered at each of the 6 cognitive test battery assessments. The sequence of forms administered will be randomized. The other listed cognitive tests will be considered secondary endpoints. An additional secondary efficacy endpoint will be the Physicians Global Impression of Change which will be recorded with the same visit frequency as other cognitive tests.
In addition to the neuropsychological tests, patients will have physical examinations, electrocardiograms, and laboratory tests of blood and urine. Safety and tolerability will be monitored by clinical assessment, reporting of adverse events, and laboratory values. Patient health will be assessed at clinic visits every 3-6 weeks throughout the study. Serum pregnancy (for females of child bearing potential) will be completed at screening and at weeks 12 and 28. Urine pregnancy tests will be completed at baseline (week 0) and weeks 16 & 32. A Safety Officer will be utilized as the primary means of monitoring safety of the study. The Safety Officer will be a physician not associated with the study in any other capacity. The Safety Officer will be given periodic reports of clinical assessments, laboratory values, and adverse events.
Allocation: Randomized, Control: Placebo Control, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment
Traumatic Brain Injury
University of Missouri-Columbia
University of Missouri-Columbia
Results (where available)
- Source: http://clinicaltrials.gov/show/NCT00462228
- Information obtained from ClinicalTrials.gov on July 15, 2010
Medical and Biotech [MESH] Definitions
AMANTADINE derivative that has some dopaminergic effects. It has been proposed as an antiparkinson agent.
Coma, Post-head Injury
Prolonged unconsciousness from which the individual cannot be aroused, associated with traumatic injuries to the BRAIN. This may be defined as unconsciousness persisting for 6 hours or longer. Coma results from injury to both cerebral hemispheres or the RETICULAR FORMATION of the BRAIN STEM. Contributing mechanisms include DIFFUSE AXONAL INJURY and BRAIN EDEMA. (From J Neurotrauma 1997 Oct;14(10):699-713)
Acute and chronic (see also BRAIN INJURIES, CHRONIC) injuries to the brain, including the cerebral hemispheres, CEREBELLUM, and BRAIN STEM. Clinical manifestations depend on the nature of injury. Diffuse trauma to the brain is frequently associated with DIFFUSE AXONAL INJURY or COMA, POST-TRAUMATIC. Localized injuries may be associated with NEUROBEHAVIORAL MANIFESTATIONS; HEMIPARESIS, or other focal neurologic deficits.
Head Injuries, Closed
Traumatic injuries to the cranium where the integrity of the skull is not compromised and no bone fragments or other objects penetrate the skull and dura mater. This frequently results in mechanical injury being transmitted to intracranial structures which may produce traumatic brain injuries, hemorrhage, or cranial nerve injury. (From Rowland, Merritt's Textbook of Neurology, 9th ed, p417)
Brain Hemorrhage, Traumatic
Bleeding within the brain as a result of penetrating and nonpenetrating CRANIOCEREBRAL TRAUMA. Traumatically induced hemorrhages may occur in any area of the brain, including the CEREBRUM; BRAIN STEM (see BRAIN STEM HEMORRHAGE, TRAUMATIC); and CEREBELLUM.
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