Memantine and Cognitive Dysfunction in Bipolar Disorder
Memantine is a glutamate NMDA receptor antagonist which has shown efficacy in cognitive dysfunction due to moderate to severe Alzheimer disease (Reisberg et al., 2003).
The investigators propose to treat 75 subjects with bipolar disorder with minimal mood symptoms and cognitive dysfunction with memantine or placebo. The 75 subjects will be enrolled at three sites. The same study will be performed at all three sites, with each site functioning independently of the other.
The investigators study will include objective neuropsychological testing of memory and executive functions before and after treatment, as well as ratings of mood symptoms and subjective patient ratings of memory function at every study visit.
The principal aim of this study is to measure the efficacy of memantine on improving memory function in minimally symptomatic subjects with bipolar disorder. The investigators hypothesize that in minimally symptomatic subjects with bipolar disorder memantine will be efficacious in improving cognitive functions, as measured by the difference in neuropsychological test scores at the beginning and at the end of the trial.
Secondary analyses will test the role of memantine in improving residual mood symptoms (depression and mania) in subjects with bipolar disorder.
Demonstrating the role of memantine in reducing cognitive dysfunction in minimally symptomatic subjects with bipolar disorder promises to provide important clinical information, which could lead to improvements in well-being and functional status for large populations of subjects with bipolar disorder.
There will be an optional open label 12-week extension to the study. Subjects will be restarted on memantine similar to the regimen in the first phase of the study. Subjects will meet with the investigators every four weeks (weeks 16, 20, and 24) for assessment as mentioned above. Neuropsychological testing will be repeated at week 24. It is the investigator's belief that this added timeline will better demonstrate any improvements in cognitive function.
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||This is a Placebo-controlled Study. It Will Compare the Effects of Memantine With Placebo on Cognitive Dysfunction|
- Neuropsychological Testing Battery [ Time Frame: Two times for an average of 14 weeks ] [ Designated as safety issue: No ]
|Study Start Date:||February 2006|
|Study Completion Date:||June 2010|
|Primary Completion Date:||June 2010 (Final data collection date for primary outcome measure)|
Week 0 Memantine 5 mg q.d.
Week 1 if mild side effects -continue previous dose Memantine, 5 mg q.d. if well tolerated - Memantine 5 mg b.i.d
Weeks 2-3 if well tolerated - Memantine 5 mg b.i.d - if mild side effects - continue Memantine , 5 mg b.i.d. if well tolerated - Memantine 5 mg q.a.m and 10 mg q.p.
Week 4-12 if well tolerated - Memantine 5 mg q.a.m and 10 mg q.p.m - if mild side effects - continue Memantine, 5 mg q.a.m and 10 mg q.p.m if well tolerated - Memantine 10 mg b.i.d
|Placebo Comparator: Placebo||
Week 0 placebo 5 mg q.d.
Week 1 if mild side effects -continue previous dose placebo, 5 mg q.d. if well tolerated - placebo 5 mg b.i.d
Weeks 2-3 if well tolerated - placebo 5 mg b.i.d - if mild side effects - continue placebo , 5 mg b.i.d. if well tolerated - placebo 5 mg q.a.m and 10 mg q.p.
Week 4-12 if well tolerated - placebo 5 mg q.a.m and 10 mg q.p.m - if mild side effects - continue placebo, 5 mg q.a.m and 10 mg q.p.m if well tolerated - placebo 10 mg b.i.d
Study: MEMANTINE AND COGNITIVE DYSFUNCTION IN BIPOLAR DISORDER The study design involves double-blind, prospective, and longitudinal treatment with flexible doses of memantine or placebo for 12 weeks in minimally symptomatic subjects with bipolar disorder and memory dysfunction. We will use objective neuropsychological testing of memory functions before and after treatment, as well as subjective patient ratings of memory throughout the treatment.
The primary analysis will compare neuropsychological test scores before and after treatment among subjects treated with memantine or placebo.
A minimum of 25 subjects with bipolar disorder will be enrolled. We will enroll subjects with bipolar disorder, diagnosed with the use of the Structured Clinical Interview for DSM-IV-TR Mood Module (SCID Mood Module) (screen visit only). Subjects will have baseline scores on the 17-item Hamilton Depression Rating Scale and on the Young Mania Rating Scale of 10 or lower. Both of these instruments will be administered by trained raters.
Screen: Week -2; Baseline Visit: Week 0; Visit 1Week 4; Visit 2Week 8;Visit 3Week 12
Please refer to this study by its ClinicalTrials.gov identifier: NCT00645476
|United States, California|
|Cedars-Sinai Medical Center, Department of Psychiatry Research and Behavioral Neurosciences|
|Los Angeles, California, United States, 90048|