Back to resultsMemantine for Neuroprotection and Cognitive Enhancement Following Traumatic Brain Injury
Primary Purpose
Traumatic Brain Injury
Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Memantine
Placebo
Sponsored by
About this trial
This is an interventional treatment trial for Traumatic Brain Injury focused on measuring Traumatic Brain Injury, Memantine, Memory
Eligibility Criteria
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
Sites / Locations
- Indiana University Health Facilities
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Memantine
Placebo
Arm Description
24 weeks of memantine with accelerated titration, beginning within 48 hours of injury.
24 weeks of placebo matched to memantine formulation, beginning within 48 hours of injury.
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
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.
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.
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.
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.
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.
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).
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT02240589
Brief Title
Memantine for Neuroprotection and Cognitive Enhancement Following Traumatic Brain Injury
Official Title
Memantine for Neuroprotection and Cognitive Enhancement Following Traumatic Brain Injury
Study Type
Interventional
2. Study Status
Record Verification Date
August 2017
Overall Recruitment Status
Completed
Study Start Date
December 2014 (undefined)
Primary Completion Date
April 2016 (Actual)
Study Completion Date
April 2016 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Indiana University
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Traumatic Brain Injury
Keywords
Traumatic Brain Injury, Memantine, Memory
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Memantine
Arm Type
Experimental
Arm Description
24 weeks of memantine with accelerated titration, beginning within 48 hours of injury.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
24 weeks of placebo matched to memantine formulation, beginning within 48 hours of injury.
Intervention Type
Drug
Intervention Name(s)
Memantine
Other Intervention Name(s)
Namenda
Intervention Description
Day 1 to 3: 10 mg bid memantine. Day 3 to 21: 20 mg bid memantine. Day 21 to 168: 10 mg bid memantine.
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Day 1 to 3: 10 mg bid placebo. Day 3 to 21: 20 mg bid placebo. Day 21 to 168: 10 mg bid placebo.
Primary Outcome Measure Information:
Title
California Verbal Learning Test - Second Edition (CVLT-II) - Long Delay Free Recall
Description
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
Secondary Outcome Measure Information:
Title
CVLT-II Trials 1-5 Free Recall Total
Description
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
Title
Brief Visuospatial Memory Test - Revised (BVMT-R) Delayed Recall
Description
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
Title
BVMT-R Learning
Description
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
Title
Trail Making Part B
Description
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
Title
Stroop Interference
Description
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
Title
Behavior Rating Inventory of Executive Function (BRIEF) Inhibit
Description
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
Title
Traumatic Brain Injury Quality of Life Anger (TBI QOL Anger)
Description
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Flora Hammond, MD
Organizational Affiliation
Indiana University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Indiana University Health Facilities
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Memantine for Neuroprotection and Cognitive Enhancement Following Traumatic Brain Injury
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