Effect of Namenda on Short Term Memory and Attention in Patients With Mild to Moderate Traumatic Brain Injury

NCT00462228 | Terminated Phase 4 Results

• 1 other identifier: NAM-MD-44
• Study Type: interventional
• Target: 11
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether memantine (Namenda) improves memory and attention in patients with mild to moderate traumatic brain injury.

Conditions

Traumatic Brain Injury

Keywords

traumatic brain injury; memory; attention

Outcome Measures

Primary Outcomes (4)

• Improvements From Baseline Scores After 6 and 12 Weeks of Memantine Compared to Placebo on the Hopkins Verbal Learning Test Revised (HVLT-R) Total Recall Learning Scores.

  HVLT-R Learning Scores provide a brief assessment of immediate recall, delayed recall and delayed recognition. It is administered by reading the words aloud, then asking the client to verbally repeat the list of words (immediately; then after a delay), and identify the words from a word list that is presented verbally. The HVLT-R is easy to administer and score, and is well-tolerated by even significantly-impaired individuals. Tasks include three learning trials, which, when combined produce a total recall score; a delayed recall (25-30 minute delay) trial, and a yes/no delayed recognition trial. Raw scores are derived for Total Recall, Delayed Recall, Retention (percent retained) and a Recognition Discrimination Index. These results are for the HVLT-R total recall raw learning score. The HVLT-R total recall raw learning score ranges from 0 to 36 with 36 being the highest and best possible score.

  Baseline, 6 weeks, and 12 weeks after beginning memantine or placebo

• Improvements From Baseline Scores After 6 and 12 Weeks of Memantine Compared to Placebo on the Hopkins Verbal Learning Test Revised (HVLT-R) Delayed Recall Scores.

  HVLT-R Learning Scores provide a brief assessment of immediate recall, delayed recall and delayed recognition. It is administered by reading the words aloud, then asking the client to verbally repeat the list of words (immediately; then after a delay), and identify the words from a word list that is presented verbally. The HVLT-R is easy to administer and score, and is well-tolerated by even significantly-impaired individuals. Tasks include three learning trials, which, when combined produce a total recall raw score; a delayed recall (25-30 minute delay) trial, and a yes/no delayed recognition trial. Raw scores are derived for Total Recall, Delayed Recall, Retention (percent retained) and a Recognition Discrimination Index. These scores are for the delayed recall learning raw score. The HVLT-R delayed recall raw score ranges from 0 to 12 with 12 being the highest and best possible score.

  Baseline, 6 weeks, and 12 weeks after beginning memantine or placebo

• Improvements From Baseline Scores After 6 and 12 Weeks of Memantine Compared to Placebo on the Brief VisuoSpatial Memory Test Revised (BVMT-R) Total Recall Score.

  BVMT-R total recall score. Each of the six equivalent, alternate BVMT-R stimulus forms consists of six geometric figures, printed in a 2 x 3 array, on a separate page of the Recall Stimulus Booklet. In the three Learning Trials, the respondent views the Recall Stimulus page for 10 seconds, then is asked to draw as many of the figures as possible, in their correct page locations. The total recall score is the sum of the three learning trials. After a 25-minute delay, which includes primarily verbal activities, the task is repeated. The respondent is asked to identify which of the 12 figures in the Recognition Stimulus Booklet were included in the 6 geometric figures on the original Recall Stimulus page. These scores are for the total recall raw score which ranges from 0-36 with 36 being the highest and best possible score.

  Baseline, 6 weeks, 12 weeks after beginning Namenda or placebo

• Improvements From Baseline Scores After 6 and 12 Weeks of Memantine Compared to Placebo on the Brief VisuoSpatial Memory Test Revised (BVMT-R) Delayed Recall Score.

  BVMT-R Delayed recall. Each of the six equivalent, alternate BVMT-R stimulus forms consists of six geometric figures, printed in a 2 x 3 array, on a separate page of the Recall Stimulus Booklet. In the three Learning Trials, the respondent views the Recall Stimulus page for 10 seconds, then is asked to draw as many of the figures as possible, in their correct page locations. After a 25-minute delay, which includes primarily verbal activities, the task is repeated. The respondent is asked to identify which of the 12 figures in the Recognition Stimulus Booklet were included in the 6 geometric figures on the original Recall Stimulus page. These scores are for the delayed recall raw score which ranges from 0 to 12 with 12 being the highest and best possible score.

  Baseline, 6 weeks, and 12 weeks after beginning memantine or placebo

Secondary Outcomes (4)

• Improvements From Baseline Scores After 6 and 12 Weeks of Memantine Compared to Placebo on the Trail Making Test Part A.

  baseline, 6 weeks, 12 weeks

• Improvements From Baseline Scores After 6 and 12 Weeks of Memantine Compared to Placebo on the Trail Making Test Part B.

  Baseline, 6 weeks, and 12 weeks after beginning memantine or placebo

• Improvements From Baseline Scores After 6 and 12 Weeks of Memantine Compared to Placebo on the Symbol Digit Modality Test (SDMT)Written Score.

  baseline, 6 weeks, 12 weeks

• Improvements From Baseline Scores After 6 and 12 Weeks of Memantine Compared to Placebo on the Symbol Digit Modality Test (SDMT) Oral Score.

  Baseline, 6 weeks, and 12 weeks after beginning memantine or placebo

Study Arms (2)

Memantine

EXPERIMENTAL

Subjects will be titrated up to 20 mg of memantine per day for 12 weeks, followed by placebo for 12 weeks

Drug: Memantine

Placebo

PLACEBO COMPARATOR

Subjects will be titrated up to 20 mg of placebo per day for 12 weeks, followed by memantine for 12 weeks

Drug: Placebo

Interventions

Memantine DRUG

After randomization of the subject, subjects will be titrated up to 20 mg of memantine or placebo per day. Memantine and placebo are provided as 5 mg tablets. Subjects will be started at 5 mg per day. The dose will be increased by 5 mg increments to 10 mg per day (5 mg twice per day), 15 mg per day (5 mg and 10 mg as separate doses) and 20 mg per day (10 mg twice per day). The minimum interval between dose increases will be one week. Subjects will take memantine or placebo for 12 weeks during each part of the crossover study. Subjects are randomized to begin either memantine or placebo in each arm of the study.

Also known as: Namenda

Memantine

Placebo DRUG

After randomization of the subject, subjects will be titrated up to 20 mg of memantine or placebo per day. Memantine and placebo are provided as 5 mg tablets. Subjects will be started at 5 mg per day. The dose will be increased by 5 mg increments to 10 mg per day (5 mg twice per day), 15 mg per day (5 mg and 10 mg as separate doses) and 20 mg per day (10 mg twice per day). The minimum interval between dose increases will be one week. Subjects will take memantine or placebo for 12 weeks during each part of the crossover study. Subjects are randomized to begin either memantine or placebo in each arm of the study.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Patients will have persistent memory and attention deficits due to a closed traumatic brain injury not less than one year prior to entrance in the study.
• Meet or exceed American Congress of Rehabilitation Medicine (ACRM) criteria for mild TBI.
• Mini-Mental State Exam (MMSE) score of 20 to 27 at the screening visit or a California Verbal Learning Test (CVLT) score for trials 1-5 one standard deviation lower than the age matched normative score. The CVLT score from the medical record may be used for entry criteria if it was obtained one year or more post-TBI and within two years of study entry.
• Galveston Orientation and Amnesia Test (GOAT) score of at least 75.
• Be of sufficient cognitive ability to complete neuropsychological tests.
• Male or female, 18-50 years of age.
• Females of childbearing potential must use acceptable means of birth control and have a negative screening beta-human chorionic gonadotrophin (b-HCG) pregnancy test. Acceptable birth control includes hormonal birth control (such as oral birth control pills, implanted or injected contraceptives), an intrauterine device (IUD), surgical sterilization (such as tubal ligation or hysterectomy), a spermicide with barrier methods (condoms or diaphragm), or a partner who has had a vasectomy.
• Patients taking donepezil (Aricept) or rivastigmine (Exelon) must be at a steady state dose for a minimum of six months.
• Patients taking any other medication(s) affecting cognition must be at a steady state dose for a minimum of two months.
• Able to provide written informed consent.
• Able to read, write, and speak in English.
• Willing and able to comply with the physician's instructions for all aspects of the study.

You may not qualify if:

• Patients must not have any medical or psychiatric disorder that in the opinion of the PI would interfere with or bias the assessment of efficacy or place their health at risk when placed on the memantine (Namenda) regimen.
• Patients with a history of seizure are excluded.
• Patients with a history of severe renal insufficiency are excluded.
• Patients must not have taken any experimental drug within the last 30 days prior to entering the protocol.
• Patients must not have taken any drug known to have major organ system toxicity within the last 30 days prior to entering the protocol.
• Women who are pregnant, nursing, or intend to become pregnant during the study are excluded.
• Patients with a penetrating TBI are excluded.
• Patients whose screening laboratory values are 1.5 times greater than upper limits of normal range(ULN) are excluded.
• Patients with systolic blood pressure greater than 180 mm Hg or less than 90 mm Hg or diastolic blood pressure greater than 105 mm Hg or less than 50 mm Hg at the screening visit are excluded.
• Concomitant use of amantadine (Symmetrel) is prohibited and a washout period of 4 weeks is required before study entry.

Sponsors & Collaborators

• University of Missouri-Columbia: lead
• Forest Laboratories: collaborator

Study Sites (1)

University of Missouri-Columbia

Columbia, Missouri, 65212, United States

Location

MeSH Terms

Conditions

Brain Injuries, Traumatic

Interventions

Memantine

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Limitations and Caveats

The enrollment goal for the study was 20 subjects. The study included 11 subjects but was terminated due to a lack of additional subjects.

Results Point of Contact

• Title: Dr. S. Jon Rupright
• Organization: Department of Physical Medicine and Rehabilitation, University of Missouri

RuprightJ@health.missouri.edu

573-882-3101

Study Officials

• S. Jon Rupright, D.O.

  Associate Professer, Clinical Physical Medicine & Rehabilitation, School of Medicine, University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

• George R. Johnstone, Ph.D.

  Professor, Department of Health Psychology, University of Missouri-Columbia

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2007
• First Posted: April 18, 2007
• Study Start: April 1, 2007
• Primary Completion: December 1, 2010
• Study Completion: December 1, 2010
• Last Updated: January 23, 2017
• Results First Posted: November 18, 2013

Record last verified: 2016-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)