Memantine and Cognitive Dysfunction in Bipolar Disorder

This study has been completed.
Sponsor:
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Andrew A. Nierenberg, MD, Massachusetts General Hospital
ClinicalTrials.gov Identifier:
NCT00586066
First received: December 21, 2007
Last updated: July 1, 2013
Last verified: July 2013
  Purpose

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

We hypothesize that in subjects 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.


Condition Intervention Phase
Bipolar Disorder
Drug: Memantine
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Memantine and Cognitive Dysfunction in Bipolar Disorder

Resource links provided by NLM:


Further study details as provided by Massachusetts General Hospital:

Primary Outcome Measures:
  • California Verbal Learning Test [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Rapid Visual Information Processing Task [ Time Frame: 4 months ] [ Designated as safety issue: No ]

Enrollment: 40
Study Start Date: November 2005
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Placebo Comparator: Placebo
Inactive comparator
Drug: Placebo
Inactive comparator
Other Name: Sugar pill
Experimental: Memantine
Repurposed Alzheimer's drug to treat cognitive dysfunction associated with bipolar disorder
Drug: Memantine
Week 0 - 5mg Memantine or placebo q.d. Week 1 - 5mg Memantine or placebo b.i.d. Week 2-3 - 5mg Memantine or placebo q.a.m./10mg q.p.m. Week 4-12 - 10mg Memantine or placebo b.i.d.
Other Name: Memantine, Namenda

Detailed Description:

A large proportion of subjects 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 subject'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 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.

  Eligibility

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

Inclusion Criteria:

  • Diagnostic and Statistical Manual-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 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:

  • 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, 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 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
  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: NCT00586066

Locations
United States, California
Cedars Sinai Department of Psychiatry
Los Angeles, California, United States, 90048
United States, Illinois
Asher Depression Center, Northwestern University
Chicago, Illinois, United States, 60611
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Sponsors and Collaborators
Massachusetts General Hospital
Forest Laboratories
Investigators
Principal Investigator: Andrew A. Nierenberg, M.D. Massachusetts General Hospital
  More Information

No publications provided

Responsible Party: Andrew A. Nierenberg, MD, Director, Bipolar Clinic and Research Program, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00586066     History of Changes
Other Study ID Numbers: 2005-p-001651
Study First Received: December 21, 2007
Last Updated: July 1, 2013
Health Authority: United States: Federal Government

Keywords provided by Massachusetts General Hospital:
Bipolar disorder
Cognitive dysfunction
Memantine
NMDA antagonist

Additional relevant MeSH terms:
Disease
Bipolar Disorder
Cognition Disorders
Pathologic Processes
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 September 18, 2014