Memantine and Cognitive Dysfunction in Bipolar Disorder

NCT00586066 | Completed Phase 4 Results DMC

• 1 other identifier: 2005-p-001651
• Study Type: interventional
• Target: 72
• Locations: 1 country
• Sites: 3

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.

Conditions

Bipolar Disorder

Keywords

Bipolar disorder; Cognitive dysfunction; Memantine; NMDA antagonist

Outcome Measures

Primary Outcomes (2)

• 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.

  Week 12

• 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.

  Week 6

Secondary Outcomes (1)

• Rapid Visual Information Processing Task (RVP)

  Weeks 6 and 12

Study Arms (2)

Placebo

PLACEBO COMPARATOR

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

Memantine

EXPERIMENTAL

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

Interventions

Memantine 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.

Also known as: Namenda

Memantine

Placebo DRUG

Inactive comparator. Placebo-matching memantine tablet.

Also known as: Sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Massachusetts General Hospital: lead
• Forest Laboratories: collaborator

Study Sites (3)

Cedars Sinai Department of Psychiatry

Los Angeles, California, 90048, United States

Location

Asher Depression Center, Northwestern University

Chicago, Illinois, 60611, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

MeSH Terms

Conditions

Bipolar Disorder; Cognitive Dysfunction

Interventions

Memantine; Sugars

Condition Hierarchy (Ancestors)

Bipolar and Related Disorders; Mood Disorders; Mental Disorders; Cognition Disorders; Neurocognitive Disorders

Intervention Hierarchy (Ancestors)

Amantadine; Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Carbohydrates

Results Point of Contact

• Title: Andrew Nierenberg, Principal Investigator
• Organization: Massachusetts General Hospital

anierenberg@partners.org

6177240837

Study Officials

• Andrew A. Nierenberg, M.D.

  Massachusetts General Hospital

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director, Bipolar Clinic and Research Program

Study Record Dates

• First Submitted: December 21, 2007
• First Posted: January 4, 2008
• Study Start: November 1, 2005
• Primary Completion: December 1, 2009
• Study Completion: December 1, 2009
• Last Updated: October 6, 2017
• Results First Posted: May 5, 2017

Record last verified: 2017-09

Locations

US (3)