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Memantine and Cognitive Dysfunction in Bipolar Disorder

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT00586066
First Posted: January 4, 2008
Last Update Posted: October 6, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborator:
Forest Laboratories
Information provided by (Responsible Party):
Andrew A. Nierenberg, MD, Massachusetts General Hospital
  Purpose

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.


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

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, 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 Andrew A. Nierenberg, MD, Massachusetts General Hospital:

Primary Outcome Measures:
  • California Verbal Learning Test (CVLT) at Week 12 [ Time Frame: Week 12 ]
    The CVLT is used to measure verbal learning and episodic long-term memory. It assesses learning, short- and long-delayed recall and recognition for a list of 16 shopping items. Subjects are expected to remember a list of words. They are asked to repeat the words remembered 5 times (5 trials). Each of the words correctly remembered, in each trial, is marked as 1 point. The reported data represent the number of correct items for the Trial 1, Trial 5, Short Delay Free Recall, and Long Delay Free Recall. The long-delayed recall is assessed at 20 minutes. The CVLT enables a comprehensive characterization of a participant's memory profile.

  • California Verbal Learning Test (CVLT) at Week 6 [ Time Frame: Week 6 ]
    The CVLT is used to measure verbal learning and episodic long-term memory. It assesses learning, short- and long-delayed recall and recognition for a list of 16 shopping items. Subjects are expected to remember a list of words. They are asked to repeat the words remembered 5 times (5 trials). Each of the words correctly remembered, in each trial, is marked as 1 point. The reported data represent the number of correct items for the Trial 1, Trial 5, Short Delay Free Recall, and Long Delay Free Recall. The long-delayed recall is assessed at 20 minutes. The CVLT enables a comprehensive characterization of a participant's memory profile.


Secondary Outcome Measures:
  • Rapid Visual Information Processing Task (RVP) [ Time Frame: Weeks 6 and 12 ]

    RVP is a sensitive measure of sustained attention. In this test, a white box appears in the center of the screen with digits from 2-9 in a pseudorandom order at a rate of 100 digits per minute. Participants are asked to identify target sequences of three digits and to register responses using the press pad.

    RVPA is a measure of target sensitivity (i.e., the ability to discriminate between target and distractors). The outcome is defined as a z-score (statistical deviation from normal). A z-score of 0 is average. Higher z-scores represent better than average performance and negative z-scores represent worse than average performance.

    RVPB is an index of response bias (i.e., the tendency to respond or not respond in general). The outcome is defined as a z-score (statistical deviation from normal). A z-score of 0 is average. Higher z-scores represent a stronger tendency to respond and negative z-scores represent a less than average tendency to respond.



Enrollment: 72
Actual 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
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.
Drug: Placebo
Inactive comparator. Placebo-matching memantine tablet.
Other Name: Sugar pill
Experimental: 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.
Drug: 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.
Other Name: Namenda

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.

  Eligibility

Information from the National Library of Medicine

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, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 65 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Responsible Party: Andrew A. Nierenberg, MD, Director, Bipolar Clinic and Research Program, Massachusetts General Hospital
ClinicalTrials.gov Identifier: NCT00586066     History of Changes
Obsolete Identifiers: NCT00645476
Other Study ID Numbers: 2005-p-001651
First Submitted: December 21, 2007
First Posted: January 4, 2008
Results First Submitted: March 24, 2017
Results First Posted: May 5, 2017
Last Update Posted: October 6, 2017
Last Verified: September 2017

Keywords provided by Andrew A. Nierenberg, MD, Massachusetts General Hospital:
Bipolar disorder
Cognitive dysfunction
Memantine
NMDA antagonist

Additional relevant MeSH terms:
Disease
Bipolar Disorder
Cognitive Dysfunction
Pathologic Processes
Bipolar and Related Disorders
Mental Disorders
Cognition Disorders
Neurocognitive Disorders
Memantine
Antiparkinson Agents
Anti-Dyskinesia Agents
Dopamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents