Memantine and Cognitive Dysfunction in Bipolar Disorder

This study has been completed.
Sponsor:
Collaborators:
Forest Laboratories
Massachusetts General Hospital
Northwestern University
Information provided by:
Cedars-Sinai Medical Center
ClinicalTrials.gov Identifier:
NCT00645476
First received: March 24, 2008
Last updated: March 26, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention
Bipolar Disorder
Drug: Memantine
Drug: Placebo

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by Cedars-Sinai Medical Center:

Primary Outcome Measures:
  • Neuropsychological Testing Battery [ Time Frame: Two times for an average of 14 weeks ] [ Designated as safety issue: No ]

Enrollment: 47
Study Start Date: February 2006
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Memantine Drug: Memantine

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 Drug: 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


Detailed Description:

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.

Visit Timeline:

Screen: Week -2; Baseline Visit: Week 0; Visit 1Week 4; Visit 2Week 8;Visit 3Week 12

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

Inclusion criteria: the following conditions must be met for patient eligibility:

  • DSM-IV diagnostic criteria for any bipolar disorder (type I, type II, and NOS) (diagnosed with the use of the Structured Clinical Interview for DSM-IV-TR Mood Module (SCID Mood Module)
  • Written informed consent
  • Men or women aged 18-65
  • A baseline Hamilton-D 17 score of < 10 at screen and baseline visits.
  • A baseline YMRS score of < 10 at screen and baseline visits.
  • No acute episodes of depression or mania for the previous 12 weeks.
  • MGH Cognitive and Physical Functioning Scale: Cut-off : >15 or
  • Everyday Cognition Self-Report Form: Average of all items >1.5 orRBANS:

    • <12 years education, RBANS total scale score of <85
    • =12 years education, RBANS total scale score of <93
    • >12 years education, RBANS total scale score of <100
  • Able to read and understand English.

Exclusion Criteria:

Patients meeting any of the following criteria will be excluded from the study:

  • Subjects with suicidal ideation where outpatient treatment is determined unsafe by the study clinician. These patients will be immediately referred to appropriate clinical treatment.
  • Pregnant women, nursing mothers, or women of childbearing potential who are not using a medically accepted means of contraception (defined as oral contraceptive pill or implant, condom, diaphragm, spermicide, IUD, s/p tubal ligation, partner with vasectomy).
  • Serious or unstable medical illness, including liver impairment, kidney impairment, cardiovascular, hepatic, respiratory, endocrine, neurologic or hematologic disease.
  • History of seizure disorder, brain injury, any history of known neurological disease (multiple sclerosis, degenerative disease such as ALS, Parkinson disease and any movement disorders, etc).
  • History or current diagnosis of the following DSM-IV psychiatric illness: organic mental disorder, schizophrenia, schizoaffective disorder, delusional disorder, psychotic disorders not otherwise specified, major depressive disorder, patients with substance dependence disorders, including alcohol, active within the last 12 months.
  • History of multiple adverse drug reactions.
  • Patients with mood congruent or mood incongruent psychotic features within the last 12 months.
  • Clinical or laboratory evidence of hypothyroidism.
  • Patients who have had an episode of acute depression or mania during the 12 weeks prior to enrollment.
  • Patients who have had electroconvulsive therapy (ECT) within the 6 months preceding enrollment.
  • Patients taking drugs which alkalinize the urine (e.g., carbonic anhydrase inhibitors, sodium bicarbonate)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00645476

Locations
United States, California
Cedars-Sinai Medical Center, Department of Psychiatry Research and Behavioral Neurosciences
Los Angeles, California, United States, 90048
Sponsors and Collaborators
Cedars-Sinai Medical Center
Forest Laboratories
Massachusetts General Hospital
Northwestern University
  More Information

No publications provided

Responsible Party: A.Fan, M.D,, Cedars-Sinai Medical Center Research Department of Psychiatry and Behavavioral Neurosciences
ClinicalTrials.gov Identifier: NCT00645476     History of Changes
Other Study ID Numbers: NAM-MD-31C
Study First Received: March 24, 2008
Last Updated: March 26, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Cedars-Sinai Medical Center:
DSM-IV diagnostic criteria for any bipolar disorder (type I, type II, and NOS)
(diagnosed with the use of the Structured Clinical Interview for DSM-IV-TR Mood Module (SCID Mood Module)

Additional relevant MeSH terms:
Bipolar Disorder
Cognition Disorders
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Delirium, Dementia, Amnestic, Cognitive Disorders
Memantine
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents

ClinicalTrials.gov processed this record on August 25, 2014