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The purpose of this study is to determine if memantine can improve cognitive and neuropsychiatric outcomes after severe traumatic brain injury.
This is a pilot/feasibility study of memantine in severe traumatic brain injury (TBI) persons, employing a randomized, double-blind, placebo-controlled, design. Outcome evaluations will occur after 24 weeks of treatment (on medication) and 4 weeks after treatment discontinuation.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Memantine | Experimental | 24 weeks of memantine with accelerated titration, beginning within 48 hours of injury. |
|
| Placebo | Placebo Comparator | 24 weeks of placebo matched to memantine formulation, beginning within 48 hours of injury. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Memantine | Drug | Day 1 to 3: 10 mg bid memantine. Day 3 to 21: 20 mg bid memantine. Day 21 to 168: 10 mg bid memantine. |
|
| Measure | Description | Time Frame |
|---|---|---|
| California Verbal Learning Test - Second Edition (CVLT-II) - Long Delay Free Recall | Neuropsychological test used to assess an individual's verbal memory abilities. The California Verbal Learning Test-Second Edition (CVLT-II) Long Delay Free Recall measures total word list items recalled after a 20-minute delay. The raw score is converted to a Z-score (Mean=0; SD=1) which was used for statistical analysis. Higher scores reflect worse performance (i.e., more recall errors) on this variable. | Week 24 |
| Measure | Description | Time Frame |
|---|---|---|
| CVLT-II Trials 1-5 Free Recall Total | Neuropsychological test used to assess an individual's verbal memory abilities. California Verbal Learning Test-Second Edition (CVLT-II) Trials 1-5 Free Recall Total measures the sum of all word list items correctly recalled on learning trials 1 through 5. This raw score is converted to a T-score (Mean=50; SD=10) which was used for statistical analysis. The total A1-5T score reflects accurate recall over the five learning trials of the first list, and is most often used as a summary index of learning on the CVLT-II, with higher scores reflecting better performance. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Flora Hammond, MD | Indiana University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Indiana University Health Facilities | Indianapolis | Indiana | 46202 | United States |
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| ID | Title | Description |
|---|---|---|
| FG000 | Memantine | 24 weeks of memantine with accelerated titration, beginning within 48 hours of injury. Memantine: Day 1 to 3: 10 mg bid memantine. Day 3 to 21: 20 mg bid memantine. Day 21 to 168: 10 mg bid memantine. |
| FG001 | Placebo | 24 weeks of placebo matched to memantine formulation, beginning within 48 hours of injury. Placebo: Day 1 to 3: 10 mg bid placebo. Day 3 to 21: 20 mg bid placebo. Day 21 to 168: 10 mg bid placebo. |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Memantine | 24 weeks of memantine with accelerated titration, beginning within 48 hours of injury. Memantine: Day 1 to 3: 10 mg bid memantine. Day 3 to 21: 20 mg bid memantine. Day 21 to 168: 10 mg bid memantine. |
| BG001 | Placebo |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | California Verbal Learning Test - Second Edition (CVLT-II) - Long Delay Free Recall | Neuropsychological test used to assess an individual's verbal memory abilities. The California Verbal Learning Test-Second Edition (CVLT-II) Long Delay Free Recall measures total word list items recalled after a 20-minute delay. The raw score is converted to a Z-score (Mean=0; SD=1) which was used for statistical analysis. Higher scores reflect worse performance (i.e., more recall errors) on this variable. | Posted | Mean | Standard Deviation | z-score | Week 24 |
|
6 months
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Memantine | 24 weeks of memantine with accelerated titration, beginning within 48 hours of injury. Memantine: Day 1 to 3: 10 mg bid memantine. Day 3 to 21: 20 mg bid memantine. Day 21 to 168: 10 mg bid memantine. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Death due to withdrawal of care | Nervous system disorders | Non-systematic Assessment | withdrawal of care |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Intracranial hypertension | Nervous system disorders | Non-systematic Assessment |
Small sample size.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Flora Hammond, MD | Indiana University School of Medicine | 317-329-2106 | flora.hammond@rhin.com |
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| ID | Term |
|---|---|
| D000070642 | Brain Injuries, Traumatic |
| ID | Term |
|---|---|
| D001930 | Brain Injuries |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| ID | Term |
|---|---|
| D008559 | Memantine |
| ID | Term |
|---|---|
| D000547 | Amantadine |
| D000218 | Adamantane |
| D001952 | Bridged-Ring Compounds |
| D006844 | Hydrocarbons, Cyclic |
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| Placebo | Drug | Day 1 to 3: 10 mg bid placebo. Day 3 to 21: 20 mg bid placebo. Day 21 to 168: 10 mg bid placebo. |
|
| Week 24 |
| Brief Visuospatial Memory Test - Revised (BVMT-R) Delayed Recall | Brief Visuospatial Memory Test-Revised (BVMT-R) Delayed Recall measures the correctly recalled designs (i.e., standard scoring of accuracy and location as described in the manual) after a 25 minute delay. The delayed recall raw score ranges from 0 to 12 with 12 being the highest and best possible score. The raw score is converted to a T-score (Mean=50; SD=10) which was used for statistical analysis. | Week 24 |
| BVMT-R Learning | Brief Visuospatial Memory Test-Revised (BVMT-R) Learning measures the correctly recalled designs (i.e., standard scoring of accuracy and location as described in the manual) over 3 learning trials. The Learning raw score is the sum of the higher number of correctly recalled designs on either Trial 2 or Trial 3 minus the number of correctly recalled designs on Trial 1. A higher score is a better score. The raw score was converted to a T-score (Mean=50; SD=10) for analysis. | Week 24 |
| Trail Making Part B | Neuropsychological test of visual attention and executive functioning. The trail making tests are thought to reflect a variety of cognitive processes including attention, visual search and scanning, sequencing and shifting, psychomotor speed, abstraction, flexibility, ability to execute and modify a plan of action, and ability to maintain two trains of thought simultaneously. In Trails B, the participant is instructed to draw lines to connect numbers and letters in an alternating numeric and alphabetic sequence as rapidly as possible. Lower scores are better scores and the range of scores can be from 0 to no limit for Trail Making Test part B. This is a timed test and the number of seconds to complete the task is recorded. The unit of measure in seconds is converted to a scaled score (mean =10, SD = 3) using the Heaton et al. norms with lower scores indicating better performance. | Week 24 |
| Stroop Interference | Stroop Interference Test is a neuropsychological test to assess a person's executive function. Specifically, the test is thought to reflect selective attention, cognitive flexibility and processing speed. The raw score for this measure is the number of items correctly identified within 45 seconds. The raw score was converted to a T-score (mean=50; SD=10) for analysis. Higher scores reflect better performance and less interference on reading ability. | Week 24 |
| Behavior Rating Inventory of Executive Function (BRIEF) Inhibit | The Behavior Rating Inventory of Executive Function (BRIEF) Inhibit subscale is a rating scale completed by the participant and independently by an observer that assesses the ability to control impulses (inhibitory control) and to stop engaging in a behavior. The frequency of behaviors indicated by items is rated on a 3-point scale (never, sometimes, often). The raw score for the Inhibit subscale is the sum of ratings for the 8 items included in this measure. This sum was converted to a T-score (mean=50; SD=10) for analysis. Higher scores suggest a higher level of dysfunction in a specific domain of executive functions. | Week 24 |
| Traumatic Brain Injury Quality of Life Anger (TBI QOL Anger) | The TBI-QOL Anger item bank includes 38 hierarchically ordered items designed to measure the full continuum of anger in a way which is both sensitive and appropriate for TBI. The TBI-QOL Anger item bank can be administered as a computer-adaptive test (CAT), allowing precise measurement of self-reported anger using only 4-8 adaptively selected items. Using CAT technology, an individual participant's responses to the TBIQoL Anger scale generated a T-score (Mean=50; SD=10) with a range of 0 (lowest anger) to 100 (greatest anger). | Week 24 |
24 weeks of placebo matched to memantine formulation, beginning within 48 hours of injury.
Placebo: Day 1 to 3: 10 mg bid placebo. Day 3 to 21: 20 mg bid placebo. Day 21 to 168: 10 mg bid placebo.
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
24 weeks of placebo matched to memantine formulation, beginning within 48 hours of injury. Placebo: Day 1 to 3: 10 mg bid placebo. Day 3 to 21: 20 mg bid placebo. Day 21 to 168: 10 mg bid placebo. |
|
|
| Secondary | CVLT-II Trials 1-5 Free Recall Total | Neuropsychological test used to assess an individual's verbal memory abilities. California Verbal Learning Test-Second Edition (CVLT-II) Trials 1-5 Free Recall Total measures the sum of all word list items correctly recalled on learning trials 1 through 5. This raw score is converted to a T-score (Mean=50; SD=10) which was used for statistical analysis. The total A1-5T score reflects accurate recall over the five learning trials of the first list, and is most often used as a summary index of learning on the CVLT-II, with higher scores reflecting better performance. | Posted | Mean | Standard Deviation | t-score | Week 24 |
|
|
|
| Secondary | Brief Visuospatial Memory Test - Revised (BVMT-R) Delayed Recall | Brief Visuospatial Memory Test-Revised (BVMT-R) Delayed Recall measures the correctly recalled designs (i.e., standard scoring of accuracy and location as described in the manual) after a 25 minute delay. The delayed recall raw score ranges from 0 to 12 with 12 being the highest and best possible score. The raw score is converted to a T-score (Mean=50; SD=10) which was used for statistical analysis. | Posted | Mean | Standard Deviation | t-score | Week 24 |
|
|
|
| Secondary | BVMT-R Learning | Brief Visuospatial Memory Test-Revised (BVMT-R) Learning measures the correctly recalled designs (i.e., standard scoring of accuracy and location as described in the manual) over 3 learning trials. The Learning raw score is the sum of the higher number of correctly recalled designs on either Trial 2 or Trial 3 minus the number of correctly recalled designs on Trial 1. A higher score is a better score. The raw score was converted to a T-score (Mean=50; SD=10) for analysis. | Posted | Mean | Standard Deviation | t-score | Week 24 |
|
|
|
| Secondary | Trail Making Part B | Neuropsychological test of visual attention and executive functioning. The trail making tests are thought to reflect a variety of cognitive processes including attention, visual search and scanning, sequencing and shifting, psychomotor speed, abstraction, flexibility, ability to execute and modify a plan of action, and ability to maintain two trains of thought simultaneously. In Trails B, the participant is instructed to draw lines to connect numbers and letters in an alternating numeric and alphabetic sequence as rapidly as possible. Lower scores are better scores and the range of scores can be from 0 to no limit for Trail Making Test part B. This is a timed test and the number of seconds to complete the task is recorded. The unit of measure in seconds is converted to a scaled score (mean =10, SD = 3) using the Heaton et al. norms with lower scores indicating better performance. | Posted | Mean | Standard Deviation | scaled score | Week 24 |
|
|
|
| Secondary | Stroop Interference | Stroop Interference Test is a neuropsychological test to assess a person's executive function. Specifically, the test is thought to reflect selective attention, cognitive flexibility and processing speed. The raw score for this measure is the number of items correctly identified within 45 seconds. The raw score was converted to a T-score (mean=50; SD=10) for analysis. Higher scores reflect better performance and less interference on reading ability. | Posted | Mean | Standard Deviation | t-score | Week 24 |
|
|
|
| Secondary | Behavior Rating Inventory of Executive Function (BRIEF) Inhibit | The Behavior Rating Inventory of Executive Function (BRIEF) Inhibit subscale is a rating scale completed by the participant and independently by an observer that assesses the ability to control impulses (inhibitory control) and to stop engaging in a behavior. The frequency of behaviors indicated by items is rated on a 3-point scale (never, sometimes, often). The raw score for the Inhibit subscale is the sum of ratings for the 8 items included in this measure. This sum was converted to a T-score (mean=50; SD=10) for analysis. Higher scores suggest a higher level of dysfunction in a specific domain of executive functions. | Posted | Mean | Standard Deviation | t-score | Week 24 |
|
|
|
| Secondary | Traumatic Brain Injury Quality of Life Anger (TBI QOL Anger) | The TBI-QOL Anger item bank includes 38 hierarchically ordered items designed to measure the full continuum of anger in a way which is both sensitive and appropriate for TBI. The TBI-QOL Anger item bank can be administered as a computer-adaptive test (CAT), allowing precise measurement of self-reported anger using only 4-8 adaptively selected items. Using CAT technology, an individual participant's responses to the TBIQoL Anger scale generated a T-score (Mean=50; SD=10) with a range of 0 (lowest anger) to 100 (greatest anger). | Posted | Mean | Standard Deviation | scaled score | Week 24 |
|
|
|
| 0 |
| 5 |
| 0 |
| 5 |
| 5 |
| 5 |
| EG001 | Placebo | 24 weeks of placebo matched to memantine formulation, beginning within 48 hours of injury. Placebo: Day 1 to 3: 10 mg bid placebo. Day 3 to 21: 20 mg bid placebo. Day 21 to 168: 10 mg bid placebo. | 1 | 6 | 1 | 6 | 6 | 6 |
|
| Pneumonia | Infections and infestations | Non-systematic Assessment |
|
| Conjuectivitis | Infections and infestations | Non-systematic Assessment |
|
| Wound infection | Infections and infestations | Non-systematic Assessment |
|
| Other, infection | Infections and infestations | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | Non-systematic Assessment |
|
| diarrhea | Gastrointestinal disorders | Non-systematic Assessment |
|
| anemia | Blood and lymphatic system disorders | Non-systematic Assessment |
|
| emesis | Gastrointestinal disorders | Non-systematic Assessment |
|
| Neurostorming | Nervous system disorders | Non-systematic Assessment |
|
| Agitation | Nervous system disorders | Non-systematic Assessment |
|
| Headache | Nervous system disorders | Non-systematic Assessment |
|
| seizures | Nervous system disorders | Non-systematic Assessment |
|
| rash | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
| anxiety | Psychiatric disorders | Non-systematic Assessment |
|
| lethargy | Nervous system disorders | Non-systematic Assessment |
|
| fatigue | Nervous system disorders | Non-systematic Assessment |
|
| insomnia | Nervous system disorders | Non-systematic Assessment |
|
| dehydration | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| fall | Injury, poisoning and procedural complications | Non-systematic Assessment |
|
| pain | Nervous system disorders | Non-systematic Assessment |
|
| depression | Psychiatric disorders | Non-systematic Assessment |
|
| hyponatremia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| hypokalemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| hypophosphotemia | Metabolism and nutrition disorders | Non-systematic Assessment |
|
| hypertension | Vascular disorders | Non-systematic Assessment |
|
| indigestion | Gastrointestinal disorders | Non-systematic Assessment |
|
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| D006259 |
| Craniocerebral Trauma |
| D020196 | Trauma, Nervous System |
| D014947 | Wounds and Injuries |
| D006838 |
| Hydrocarbons |
| D009930 | Organic Chemicals |