Memantine and Cognitive Dysfunction in Bipolar Disorder

NCT ID: NCT00586066

Last Updated: 2017-10-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE4
• Total Enrollment: 72 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-11-30
• Study Completion Date: 2009-12-31

Brief Summary

The purpose of this study is to see whether memantine improves memory function in participants with bipolar disorder who have minimal symptoms. Secondary analyses will test the role of memantine in improving residual mood symptoms (depression and mania) in participants with bipolar disorder.

We hypothesize that in participants with bipolar disorder who have minimal symptoms memantine will be effective in improving cognitive functions, as measured by the difference in neuropsychological test scores at the beginning and at the end of the trial.

Detailed Description

A large proportion of participants with bipolar disorder experience significant cognitive dysfunction, even when euthymic, after adequate treatment. The cognitive deficits in asymptomatic patients with bipolar disorder are very important for the participant's psychosocial function. In this population, cognitive deficits have been associated with poor psychosocial functioning, such as inability to hold a job. Memantine is a glutamate N-methyl-D-aspartate (NMDA) receptor antagonist which has shown efficacy in cognitive dysfunction due to moderate to severe Alzheimer disease.

Demonstrating the role of memantine in reducing cognitive dysfunction in minimally symptomatic participants with bipolar disorder promises to provide important clinical information, which could lead to improvements in well-being and functional status for large populations of participants with bipolar disorder.

Conditions

Bipolar Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Placebo

Placebo-matching memantine 5 mg tablet once per day for 1 week; dose increase if tolerated to placebo-matching memantine 5 mg twice a day, in the morning and the evening in Week 2; dose increase if tolerated to placebo-matching memantine 5 mg in the morning and placebo-matching memantine 10 mg in the evening in Week 3; dose increase if tolerated to placebo-matching memantine 10 mg twice a day, in the morning and the evening Weeks 4 to 12.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Inactive comparator. Placebo-matching memantine tablet.

Memantine

Re-purposed Alzheimer's drug to treat cognitive dysfunction associated with bipolar disorder. Memantine 5 mg tablet once per day for 1 week; dose increase if tolerated to memantine 5 mg twice a day, in the morning and the evening in Week 2; dose increase if tolerated to memantine 5 mg in the morning and memantine 10 mg in the evening in Week 3; dose increase if tolerated to memantine 10 mg twice a day, in the morning and the evening Weeks 4 to 12.

Group Type: EXPERIMENTAL

Memantine

Intervention Type: DRUG

Week 0: 5 mg memantine or placebo once a day (q.d.) Week 1: 5 mg memantine or placebo twice a day (b.i.d.) Week 2-3: 5 mg memantine or placebo once in the morning (q.a.m.)/10 mg once in the evening (q.p.m.) Week 4-12: 10mg Memantine or placebo b.i.d.

Interventions

Memantine

Week 0: 5 mg memantine or placebo once a day (q.d.) Week 1: 5 mg memantine or placebo twice a day (b.i.d.) Week 2-3: 5 mg memantine or placebo once in the morning (q.a.m.)/10 mg once in the evening (q.p.m.) Week 4-12: 10mg Memantine or placebo b.i.d.

Intervention Type: DRUG

Placebo

Inactive comparator. Placebo-matching memantine tablet.

Intervention Type: DRUG

Other Intervention Names

Namenda; Sugar pill

Eligibility Criteria

Inclusion Criteria

• Diagnostic and Statistical Manual-IV (DSM-IV) diagnostic criteria for any bipolar disorder [type I, type II, and not otherwise specified (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 Young Mania Rating Scale score of < 10 at screen and baseline visits.
• No acute episodes of depression or mania for the previous 12 weeks.
• Massachusetts General Hospital Cognitive and Physical Functioning Scale: Cut-off: >15 or Everyday Cognition Self-Report Form: Average of all items >1.5 or Repeatable Battery for the Assessment of Neuropsychological Status (RBANS): <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:

• Participants 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, intrauterine device (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 amyotrophic lateral sclerosis (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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Forest Laboratories

INDUSTRY

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: lead

Responsible Party

Andrew A. Nierenberg, MD

Director, Bipolar Clinic and Research Program

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Andrew A. Nierenberg, M.D.

Role: PRINCIPAL_INVESTIGATOR

Massachusetts General Hospital

Locations

Cedars Sinai Department of Psychiatry

Los Angeles, California, United States

Asher Depression Center, Northwestern University

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Countries

United States

Other Identifiers

2005-p-001651

Identifier Type: -

Identifier Source: org_study_id

NCT00645476

Identifier Type: -

Identifier Source: nct_alias