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Memantine for Neuroprotection and Cognitive Enhancement Following Traumatic Brain Injury

Memantine for Neuroprotection and Cognitive Enhancement Following Traumatic Brain Injury

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02240589
Enrollment
11
Registered
2014-09-15
Start date
2014-12-31
Completion date
2016-04-30
Last updated
2017-08-30

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Traumatic Brain Injury

Keywords

Traumatic Brain Injury, Memantine, Memory

Brief summary

The purpose of this study is to determine if memantine can improve cognitive and neuropsychiatric outcomes after severe traumatic brain injury.

Detailed description

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.

Interventions

DRUGMemantine

Day 1 to 3: 10 mg bid memantine. Day 3 to 21: 20 mg bid memantine. Day 21 to 168: 10 mg bid memantine.

DRUGPlacebo

Day 1 to 3: 10 mg bid placebo. Day 3 to 21: 20 mg bid placebo. Day 21 to 168: 10 mg bid placebo.

Sponsors

Indiana University
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No

Inclusion criteria

* 18-65 years old of age at time of enrollment * Severe traumatic brain injury (TBI) * Feeding access (e.g., orogastric (OG), nasogastric (NG), or percutaneous endoscopic gastrostomy (PEG) tube) permitting delivery of memantine or placebo * Availability of legally-authorized representative (LAR) to provide consent and participate in some study activities (e.g., monitoring for side effects, providing information about the patient)

Exclusion criteria

* Pre-existing history of serious neurological disorder * Pre-existing history of serious psychiatric disorder (e.g., schizophrenia) * Anticipated poor prognosis, based on the presence of bilaterally fixed and dilated pupils, severe hemodynamic instability, severe elevations in intracranial pressure refractory to interventions, or other factors leading to a determination of a probable non-survivable injury * Primarily penetrating mechanism of injury (e.g., gunshot wound to the head) * Isolated epidural hematoma with anticipated good prognosis * Low probability of participant being compliant or being able to finish study procedures (e.g., present for outcome rating) in the judgment of the investigator * Not English speaking (due to inability to complete outcome measure) * Medical contraindications to memantine: Severe hepatic impairment (defined as albumin \> 15gm/dL, Alk Phos \> 375 U/L, ALT \> 150 U/L, AST \> 120 U/L or bilirubin \> 3mg/dL). Moderate-to-Severe renal impairment (defined as creatinine clearance \< 60) * Pregnancy or breastfeeding

Design outcomes

Primary

MeasureTime frameDescription
California Verbal Learning Test - Second Edition (CVLT-II) - Long Delay Free RecallWeek 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.

Secondary

MeasureTime frameDescription
Brief Visuospatial Memory Test - Revised (BVMT-R) Delayed RecallWeek 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.
BVMT-R LearningWeek 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.
Trail Making Part BWeek 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.
CVLT-II Trials 1-5 Free Recall TotalWeek 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.
Behavior Rating Inventory of Executive Function (BRIEF) InhibitWeek 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.
Traumatic Brain Injury Quality of Life Anger (TBI QOL Anger)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).
Stroop InterferenceWeek 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.

Countries

United States

Participant flow

Participants by arm

ArmCount
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.
5
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.
6
Total11

Baseline characteristics

CharacteristicPlaceboTotalMemantine
Age, Continuous40.83 years
STANDARD_DEVIATION 6.52
33.82 years
STANDARD_DEVIATION 14.29
25.4 years
STANDARD_DEVIATION 2.3
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants0 Participants0 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
6 Participants11 Participants5 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Asian
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Black or African American
0 Participants0 Participants0 Participants
Race (NIH/OMB)
More than one race
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants0 Participants0 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants0 Participants0 Participants
Race (NIH/OMB)
White
6 Participants11 Participants5 Participants
Sex: Female, Male
Female
4 Participants4 Participants0 Participants
Sex: Female, Male
Male
2 Participants7 Participants5 Participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
0 / 51 / 6
other
Total, other adverse events
5 / 56 / 6
serious
Total, serious adverse events
0 / 51 / 6

Outcome results

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.

Time frame: Week 24

ArmMeasureValue (MEAN)Dispersion
MemantineCalifornia Verbal Learning Test - Second Edition (CVLT-II) - Long Delay Free Recall-2.000 z-scoreStandard Deviation 1
PlaceboCalifornia Verbal Learning Test - Second Edition (CVLT-II) - Long Delay Free Recall-1.375 z-scoreStandard Deviation 2.016
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.

Time frame: Week 24

ArmMeasureValue (MEAN)Dispersion
MemantineBehavior Rating Inventory of Executive Function (BRIEF) Inhibit46.00 t-scoreStandard Deviation 9.416
PlaceboBehavior Rating Inventory of Executive Function (BRIEF) Inhibit61.00 t-scoreStandard Deviation 17.569
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.

Time frame: Week 24

ArmMeasureValue (MEAN)Dispersion
MemantineBrief Visuospatial Memory Test - Revised (BVMT-R) Delayed Recall47.00 t-scoreStandard Deviation 4.583
PlaceboBrief Visuospatial Memory Test - Revised (BVMT-R) Delayed Recall45.50 t-scoreStandard Deviation 11.561
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.

Time frame: Week 24

ArmMeasureValue (MEAN)Dispersion
MemantineBVMT-R Learning60.00 t-scoreStandard Deviation 8.266
PlaceboBVMT-R Learning46.50 t-scoreStandard Deviation 1
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.

Time frame: Week 24

ArmMeasureValue (MEAN)Dispersion
MemantineCVLT-II Trials 1-5 Free Recall Total31.000 t-scoreStandard Deviation 10.817
PlaceboCVLT-II Trials 1-5 Free Recall Total37.250 t-scoreStandard Deviation 15.262
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.

Time frame: Week 24

ArmMeasureValue (MEAN)Dispersion
MemantineStroop Interference51.67 t-scoreStandard Deviation 6.807
PlaceboStroop Interference52.25 t-scoreStandard Deviation 7.32
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.

Time frame: Week 24

ArmMeasureValue (MEAN)Dispersion
MemantineTrail Making Part B11.67 scaled scoreStandard Deviation 6.351
PlaceboTrail Making Part B13.25 scaled scoreStandard Deviation 4.349
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).

Time frame: Week 24

ArmMeasureValue (MEAN)Dispersion
MemantineTraumatic Brain Injury Quality of Life Anger (TBI QOL Anger)49.725 scaled scoreStandard Deviation 8.684
PlaceboTraumatic Brain Injury Quality of Life Anger (TBI QOL Anger)45.375 scaled scoreStandard Deviation 9.854

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026