Trial Outcomes & Findings for Memantine for Neuroprotection and Cognitive Enhancement Following Traumatic Brain Injury (NCT NCT02240589)
NCT ID: NCT02240589
Last Updated: 2017-08-30
Results Overview
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.
COMPLETED
NA
11 participants
Week 24
2017-08-30
Participant Flow
Participant milestones
| Measure |
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.
|
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.
|
|---|---|---|
|
Overall Study
STARTED
|
5
|
6
|
|
Overall Study
COMPLETED
|
3
|
4
|
|
Overall Study
NOT COMPLETED
|
2
|
2
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Memantine for Neuroprotection and Cognitive Enhancement Following Traumatic Brain Injury
Baseline characteristics by cohort
| Measure |
Memantine
n=5 Participants
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.
|
Placebo
n=6 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.
|
Total
n=11 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
25.4 years
STANDARD_DEVIATION 2.3 • n=5 Participants
|
40.83 years
STANDARD_DEVIATION 6.52 • n=7 Participants
|
33.82 years
STANDARD_DEVIATION 14.29 • n=5 Participants
|
|
Sex: Female, Male
Female
|
0 Participants
n=5 Participants
|
4 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
7 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
5 Participants
n=5 Participants
|
6 Participants
n=7 Participants
|
11 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Week 24Neuropsychological 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.
Outcome measures
| Measure |
Memantine
n=3 Participants
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.
|
Placebo
n=4 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.
|
|---|---|---|
|
California Verbal Learning Test - Second Edition (CVLT-II) - Long Delay Free Recall
|
-2.000 z-score
Standard Deviation 1.000
|
-1.375 z-score
Standard Deviation 2.016
|
SECONDARY outcome
Timeframe: Week 24Neuropsychological 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.
Outcome measures
| Measure |
Memantine
n=3 Participants
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.
|
Placebo
n=4 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.
|
|---|---|---|
|
CVLT-II Trials 1-5 Free Recall Total
|
31.000 t-score
Standard Deviation 10.817
|
37.250 t-score
Standard Deviation 15.262
|
SECONDARY outcome
Timeframe: Week 24Brief 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.
Outcome measures
| Measure |
Memantine
n=3 Participants
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.
|
Placebo
n=4 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.
|
|---|---|---|
|
Brief Visuospatial Memory Test - Revised (BVMT-R) Delayed Recall
|
47.00 t-score
Standard Deviation 4.583
|
45.50 t-score
Standard Deviation 11.561
|
SECONDARY outcome
Timeframe: Week 24Brief 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.
Outcome measures
| Measure |
Memantine
n=3 Participants
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.
|
Placebo
n=4 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.
|
|---|---|---|
|
BVMT-R Learning
|
60.00 t-score
Standard Deviation 8.266
|
46.50 t-score
Standard Deviation 1.000
|
SECONDARY outcome
Timeframe: Week 24Neuropsychological 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.
Outcome measures
| Measure |
Memantine
n=3 Participants
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.
|
Placebo
n=4 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.
|
|---|---|---|
|
Trail Making Part B
|
11.67 scaled score
Standard Deviation 6.351
|
13.25 scaled score
Standard Deviation 4.349
|
SECONDARY outcome
Timeframe: Week 24Stroop 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.
Outcome measures
| Measure |
Memantine
n=3 Participants
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.
|
Placebo
n=4 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.
|
|---|---|---|
|
Stroop Interference
|
51.67 t-score
Standard Deviation 6.807
|
52.25 t-score
Standard Deviation 7.320
|
SECONDARY outcome
Timeframe: Week 24The 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.
Outcome measures
| Measure |
Memantine
n=3 Participants
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.
|
Placebo
n=4 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.
|
|---|---|---|
|
Behavior Rating Inventory of Executive Function (BRIEF) Inhibit
|
46.00 t-score
Standard Deviation 9.416
|
61.00 t-score
Standard Deviation 17.569
|
SECONDARY outcome
Timeframe: Week 24The 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).
Outcome measures
| Measure |
Memantine
n=3 Participants
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.
|
Placebo
n=4 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.
|
|---|---|---|
|
Traumatic Brain Injury Quality of Life Anger (TBI QOL Anger)
|
49.725 scaled score
Standard Deviation 8.684
|
45.375 scaled score
Standard Deviation 9.854
|
Adverse Events
Memantine
Placebo
Serious adverse events
| Measure |
Memantine
n=5 participants at risk
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.
|
Placebo
n=6 participants at risk
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.
|
|---|---|---|
|
Nervous system disorders
Death due to withdrawal of care
|
0.00%
0/5 • 6 months
|
16.7%
1/6 • Number of events 1 • 6 months
|
Other adverse events
| Measure |
Memantine
n=5 participants at risk
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.
|
Placebo
n=6 participants at risk
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.
|
|---|---|---|
|
Nervous system disorders
Agitation
|
40.0%
2/5 • Number of events 2 • 6 months
|
33.3%
2/6 • Number of events 2 • 6 months
|
|
Nervous system disorders
Headache
|
40.0%
2/5 • Number of events 2 • 6 months
|
33.3%
2/6 • Number of events 2 • 6 months
|
|
Nervous system disorders
Intracranial hypertension
|
20.0%
1/5 • Number of events 1 • 6 months
|
0.00%
0/6 • 6 months
|
|
Infections and infestations
Pneumonia
|
60.0%
3/5 • Number of events 3 • 6 months
|
50.0%
3/6 • Number of events 3 • 6 months
|
|
Infections and infestations
Conjuectivitis
|
20.0%
1/5 • Number of events 1 • 6 months
|
0.00%
0/6 • 6 months
|
|
Infections and infestations
Wound infection
|
0.00%
0/5 • 6 months
|
16.7%
1/6 • Number of events 1 • 6 months
|
|
Infections and infestations
Other, infection
|
0.00%
0/5 • 6 months
|
33.3%
2/6 • Number of events 2 • 6 months
|
|
Gastrointestinal disorders
Constipation
|
20.0%
1/5 • Number of events 1 • 6 months
|
16.7%
1/6 • Number of events 1 • 6 months
|
|
Gastrointestinal disorders
diarrhea
|
20.0%
1/5 • Number of events 1 • 6 months
|
16.7%
1/6 • Number of events 1 • 6 months
|
|
Blood and lymphatic system disorders
anemia
|
20.0%
1/5 • Number of events 1 • 6 months
|
0.00%
0/6 • 6 months
|
|
Gastrointestinal disorders
emesis
|
40.0%
2/5 • Number of events 2 • 6 months
|
0.00%
0/6 • 6 months
|
|
Nervous system disorders
Neurostorming
|
60.0%
3/5 • Number of events 3 • 6 months
|
33.3%
2/6 • Number of events 2 • 6 months
|
|
Nervous system disorders
seizures
|
20.0%
1/5 • Number of events 1 • 6 months
|
0.00%
0/6 • 6 months
|
|
Skin and subcutaneous tissue disorders
rash
|
20.0%
1/5 • Number of events 1 • 6 months
|
16.7%
1/6 • Number of events 1 • 6 months
|
|
Psychiatric disorders
anxiety
|
0.00%
0/5 • 6 months
|
16.7%
1/6 • Number of events 1 • 6 months
|
|
Nervous system disorders
lethargy
|
0.00%
0/5 • 6 months
|
16.7%
1/6 • Number of events 1 • 6 months
|
|
Nervous system disorders
fatigue
|
20.0%
1/5 • Number of events 1 • 6 months
|
0.00%
0/6 • 6 months
|
|
Nervous system disorders
insomnia
|
20.0%
1/5 • Number of events 1 • 6 months
|
33.3%
2/6 • Number of events 2 • 6 months
|
|
Metabolism and nutrition disorders
dehydration
|
60.0%
3/5 • Number of events 3 • 6 months
|
0.00%
0/6 • 6 months
|
|
Injury, poisoning and procedural complications
fall
|
0.00%
0/5 • 6 months
|
33.3%
2/6 • Number of events 3 • 6 months
|
|
Nervous system disorders
pain
|
40.0%
2/5 • Number of events 2 • 6 months
|
16.7%
1/6 • Number of events 1 • 6 months
|
|
Psychiatric disorders
depression
|
0.00%
0/5 • 6 months
|
16.7%
1/6 • Number of events 1 • 6 months
|
|
Metabolism and nutrition disorders
hyponatremia
|
20.0%
1/5 • Number of events 1 • 6 months
|
0.00%
0/6 • 6 months
|
|
Metabolism and nutrition disorders
hypokalemia
|
0.00%
0/5 • 6 months
|
16.7%
1/6 • Number of events 1 • 6 months
|
|
Metabolism and nutrition disorders
hypophosphotemia
|
0.00%
0/5 • 6 months
|
16.7%
1/6 • Number of events 1 • 6 months
|
|
Vascular disorders
hypertension
|
0.00%
0/5 • 6 months
|
16.7%
1/6 • Number of events 1 • 6 months
|
|
Gastrointestinal disorders
indigestion
|
0.00%
0/5 • 6 months
|
16.7%
1/6 • Number of events 1 • 6 months
|
Additional Information
Flora Hammond, MD
Indiana University School of Medicine
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place