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Memantine and Cognitive Dysfunction in Bipolar Disorder

Primary Purpose

Bipolar Disorder

Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Memantine
Placebo
Sponsored by
Massachusetts General Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Bipolar Disorder focused on measuring Bipolar disorder, Cognitive dysfunction, Memantine, NMDA antagonist

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Cedars Sinai Department of Psychiatry
  • Asher Depression Center, Northwestern University
  • Massachusetts General Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Placebo Comparator

Experimental

Arm Label

Placebo

Memantine

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

California Verbal Learning Test (CVLT) at 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
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)
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.

Full Information

First Posted
December 21, 2007
Last Updated
September 7, 2017
Sponsor
Massachusetts General Hospital
Collaborators
Forest Laboratories
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1. Study Identification

Unique Protocol Identification Number
NCT00586066
Brief Title
Memantine and Cognitive Dysfunction in Bipolar Disorder
Official Title
Memantine and Cognitive Dysfunction in Bipolar Disorder
Study Type
Interventional

2. Study Status

Record Verification Date
September 2017
Overall Recruitment Status
Completed
Study Start Date
November 2005 (Actual)
Primary Completion Date
December 2009 (Actual)
Study Completion Date
December 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Massachusetts General Hospital
Collaborators
Forest Laboratories

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Disorder
Keywords
Bipolar disorder, Cognitive dysfunction, Memantine, NMDA antagonist

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
72 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
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.
Arm Title
Memantine
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Memantine
Other Intervention Name(s)
Namenda
Intervention Description
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
Intervention Name(s)
Placebo
Other Intervention Name(s)
Sugar pill
Intervention Description
Inactive comparator. Placebo-matching memantine tablet.
Primary Outcome Measure Information:
Title
California Verbal Learning Test (CVLT) at Week 12
Description
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.
Time Frame
Week 12
Title
California Verbal Learning Test (CVLT) at Week 6
Description
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.
Time Frame
Week 6
Secondary Outcome Measure Information:
Title
Rapid Visual Information Processing Task (RVP)
Description
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.
Time Frame
Weeks 6 and 12

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrew A. Nierenberg, M.D.
Organizational Affiliation
Massachusetts General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Cedars Sinai Department of Psychiatry
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Asher Depression Center, Northwestern University
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60611
Country
United States
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States

12. IPD Sharing Statement

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Memantine and Cognitive Dysfunction in Bipolar Disorder

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