Trial Outcomes & Findings for Memantine and Cognitive Dysfunction in Bipolar Disorder (NCT NCT00586066)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

72 participants

Primary outcome timeframe

Week 12

Results posted on

2017-10-06

Participant Flow

Recruitment began in November 2005 and closed in December 2009.

Participant milestones

Participant milestones
Measure	Memantine 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.	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.
Overall Study STARTED	48	24
Overall Study COMPLETED	30	14
Overall Study NOT COMPLETED	18	10

Reasons for withdrawal

Reasons for withdrawal
Measure	Memantine 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.	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.
Overall Study Lost to Follow-up	6	3
Overall Study Lack of Efficacy	5	3
Overall Study Adverse Event	2	2
Overall Study Physician Decision	1	0
Overall Study Withdrawal of consent	4	2

Baseline Characteristics

Memantine and Cognitive Dysfunction in Bipolar Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Memantine n=48 Participants 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.	Placebo n=24 Participants 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.	Total n=72 Participants Total of all reporting groups
Age, Continuous	46.29 years STANDARD_DEVIATION 10.48 • n=5 Participants	47.33 years STANDARD_DEVIATION 7.98 • n=7 Participants	46.70 years STANDARD_DEVIATION 9.54 • n=5 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	11 Participants n=7 Participants	35 Participants n=5 Participants
Sex: Female, Male Male	24 Participants n=5 Participants	13 Participants n=7 Participants	37 Participants n=5 Participants
Region of Enrollment United States	48 Participants n=5 Participants	24 Participants n=7 Participants	72 Participants n=5 Participants

PRIMARY outcome

Timeframe: Week 12

Population: All Randomized participants with data available 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.

Outcome measures

Outcome measures
Measure	Memantine n=26 Participants 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.	Placebo n=13 Participants 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.
California Verbal Learning Test (CVLT) at Week 12 CVLT Trial 1	11.88 correct items Standard Deviation 2.659	11.55 correct items Standard Deviation 2.505
California Verbal Learning Test (CVLT) at Week 12 CVLT Trial 5	11.63 correct items Standard Deviation 3.645	11.73 correct items Standard Deviation 3.524
California Verbal Learning Test (CVLT) at Week 12 CVLT Short Delay Free Recall	11.79 correct items Standard Deviation 3.718	12.09 correct items Standard Deviation 3.477
California Verbal Learning Test (CVLT) at Week 12 CVLT Long Delay Free Recall	14.46 correct items Standard Deviation 1.641	14.55 correct items Standard Deviation 1.128

PRIMARY outcome

Timeframe: Week 6

Population: All Randomized participants with data available 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.

Outcome measures

Outcome measures
Measure	Memantine n=41 Participants 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.	Placebo n=19 Participants 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.
California Verbal Learning Test (CVLT) at Week 6 CVLT Trial 1	11.55 correct items Standard Deviation 3.280	10.65 correct items Standard Deviation 2.849
California Verbal Learning Test (CVLT) at Week 6 CVLT Trial 5	9.15 correct items Standard Deviation 3.815	9.05 correct items Standard Deviation 3.316
California Verbal Learning Test (CVLT) at Week 6 CVLT Short Delay Free Recall	11.31 correct items Standard Deviation 4.335	10.24 correct items Standard Deviation 4.024
California Verbal Learning Test (CVLT) at Week 6 CVLT Long Delay Free Recall	14.03 correct items Standard Deviation 2.732	13.53 correct items Standard Deviation 3.826

SECONDARY outcome

Timeframe: Weeks 6 and 12

Population: All randomized participants with data available at the given time-point.

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.

Outcome measures

Outcome measures
Measure	Memantine n=48 Participants 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.	Placebo n=24 Participants 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.
Rapid Visual Information Processing Task (RVP) RVPA, Week 6	-1.3997 z-score Standard Deviation 5.23534	-0.6859 z-score Standard Deviation 0.96275
Rapid Visual Information Processing Task (RVP) RVPA, Week 12	-0.1508 z-score Standard Deviation 1.49027	-0.6017 z-score Standard Deviation 1.00486
Rapid Visual Information Processing Task (RVP) RVPB, Week 6	-2.4440 z-score Standard Deviation 7.76338	-0.2353 z-score Standard Deviation 0.74248
Rapid Visual Information Processing Task (RVP) RVPB, Week 12	-1.4833 z-score Standard Deviation 4.39216	-0.2108 z-score Standard Deviation 0.59609

Adverse Events

Memantine

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Memantine n=48 participants at risk 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.	Placebo n=24 participants at risk 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.
Gastrointestinal disorders Gastric reflux	0.00% 0/48 • 12 Weeks	8.3% 2/24 • 12 Weeks

Additional Information

Andrew Nierenberg, Principal Investigator

Massachusetts General Hospital

Phone: 6177240837

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place