Trial Outcomes & Findings for Treatment to Enhance Cognition in Bipolar Disorder (NCT NCT01470781)

Last Updated: 2021-09-28

Results Overview

The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery includes 10 tasks that are designed to measure seven key cognitive domains: processing speed, attention, working memory, verbal learning, visual learning, problem solving and social cognition. These scores are also combined to yield a cognitive Composite. All subtest, domain, and composite scores are reported in standardized T scores with a mean of 50 and a standard deviation of 10; higher scores reflect better performance. For example, a score of 60 on any subtest, domain, or the Composite would represent a score 1 standard deviation above than the mean. All standardized scores are computed by the MCCB scoring software included in the testing battery, and are normed by age and sex. Total administration time is 60-90 minutes.

Recruitment status

COMPLETED

Study phase

Target enrollment

72 participants

Primary outcome timeframe

within 1 week prior to initiating intervention; midpoint - on average 8 weeks after initiation; post-treatment - on average 24 weeks after initiation; after 6 months no active intervention

Results posted on

2021-09-28

Participant Flow

Participant milestones

Participant milestones
Measure	Cognitive Remediation This arm will receive computer-based cognitive remediation treatment 3 times per week for 24 weeks, for a total of 70 hours of treatment BrainWorks: 13 programs targeting cognition in 4 separate domains: Auditory processing, visual processing, social cognition, and executive functioning. Games are imbedded in a format that is engaging and interactive. Animated characters serve as "directors" for each program, explaining the tasks in both verbal and written formats and providing feedback on each trial and overall after each activity. Users move systematically through the programs and can track their progress as the go. Each session includes activities from several different games to maintain interest and train a variety of skills; however, games are presented in the order of domains listed above (i.e. auditory, then visual, then social, and finally executive) to avoid stimulus interference during the training.	Computer Control Group will receive 70 hours of computer time playing pre-selected computer games administered in a similar format as the Cognitive Remediation condition Computer Control: Sessions will involve generic computer games administered via the game interface "Sporcle." Sporcle is a game site that offers a collection of quiz-type activities available on line. An administrator can track the activity of subjects including when they logged in, which games they played and for how long, and what their accuracy was on each game. We will use a pre-developed game schedule that includes a mix of each type of game in each session, and ensures that subjects are playing the same games in the same order. This format was developed to mirror the treatment condition, as subjects are given a variety of specific games to play at each session.
Overall Study STARTED	39	33
Overall Study Midpoint Assessment	30	30
Overall Study Post-Treatment Assessment	22	23
Overall Study COMPLETED	21	21
Overall Study NOT COMPLETED	18	12

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Treatment to Enhance Cognition in Bipolar Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cognitive Remediation n=39 Participants This arm will receive computer-based cognitive remediation treatment 3 times per week for 24 weeks, for a total of 70 hours of treatment BrainWorks: 13 programs targeting cognition in 4 separate domains: Auditory processing, visual processing, social cognition, and executive functioning. Games are imbedded in a format that is engaging and interactive. Animated characters serve as "directors" for each program, explaining the tasks in both verbal and written formats and providing feedback on each trial and overall after each activity. Users move systematically through the programs and can track their progress as the go. Each session includes activities from several different games to maintain interest and train a variety of skills; however, games are presented in the order of domains listed above (i.e. auditory, then visual, then social, and finally executive) to avoid stimulus interference during the training.	Computer Control n=33 Participants Group will receive 70 hours of computer time playing pre-selected computer games administered in a similar format as the Cognitive Remediation condition Computer Control: Sessions will involve generic computer games administered via the game interface "Sporcle." Sporcle is a game site that offers a collection of quiz-type activities available on line. An administrator can track the activity of subjects including when they logged in, which games they played and for how long, and what their accuracy was on each game. We will use a pre-developed game schedule that includes a mix of each type of game in each session, and ensures that subjects are playing the same games in the same order. This format was developed to mirror the treatment condition, as subjects are given a variety of specific games to play at each session.	Total n=72 Participants Total of all reporting groups
Age, Continuous	29.3 years STANDARD_DEVIATION 7.5 • n=5 Participants	29.8 years STANDARD_DEVIATION 9.2 • n=7 Participants	29.6 years STANDARD_DEVIATION 8.4 • n=5 Participants
Sex: Female, Male Female	20 Participants n=5 Participants	20 Participants n=7 Participants	40 Participants n=5 Participants
Sex: Female, Male Male	19 Participants n=5 Participants	13 Participants n=7 Participants	32 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	3 Participants n=5 Participants	3 Participants n=7 Participants	6 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	36 Participants n=5 Participants	30 Participants n=7 Participants	66 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	3 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) White	29 Participants n=5 Participants	26 Participants n=7 Participants	55 Participants n=5 Participants
Race (NIH/OMB) More than one race	2 Participants n=5 Participants	2 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	39 participants n=5 Participants	33 participants n=7 Participants	72 participants n=5 Participants

PRIMARY outcome

Timeframe: within 1 week prior to initiating intervention; midpoint - on average 8 weeks after initiation; post-treatment - on average 24 weeks after initiation; after 6 months no active intervention

Population: 84 participants signed consent and met eligibility criteria; however, 12 discontinued prior to completion of the baseline assessment and therefore were not randomized and no data were available; therefore only randomized participants who completed at least one assessment were able to be included in the analyses.

Outcome measures

Outcome measures
Measure	Cognitive Remediation n=39 Participants This arm will receive computer-based cognitive remediation treatment 3 times per week for 24 weeks, for a total of 70 hours of treatment BrainWorks: 13 programs targeting cognition in 4 separate domains: Auditory processing, visual processing, social cognition, and executive functioning. Games are imbedded in a format that is engaging and interactive. Animated characters serve as "directors" for each program, explaining the tasks in both verbal and written formats and providing feedback on each trial and overall after each activity. Users move systematically through the programs and can track their progress as the go. Each session includes activities from several different games to maintain interest and train a variety of skills; however, games are presented in the order of domains listed above (i.e. auditory, then visual, then social, and finally executive) to avoid stimulus interference during the training.	Computer Control n=33 Participants Group will receive 70 hours of computer time playing pre-selected computer games administered in a similar format as the Cognitive Remediation condition Computer Control: Sessions will involve generic computer games administered via the game interface "Sporcle." Sporcle is a game site that offers a collection of quiz-type activities available on line. An administrator can track the activity of subjects including when they logged in, which games they played and for how long, and what their accuracy was on each game. We will use a pre-developed game schedule that includes a mix of each type of game in each session, and ensures that subjects are playing the same games in the same order. This format was developed to mirror the treatment condition, as subjects are given a variety of specific games to play at each session.
MATRICS Consensus Cognitive Battery (MCCB) Baseline	45.2 T-scores Standard Deviation 10.4	45.5 T-scores Standard Deviation 9.1
MATRICS Consensus Cognitive Battery (MCCB) Midpoint	47.7 T-scores Standard Deviation 10.0	49.3 T-scores Standard Deviation 8.7
MATRICS Consensus Cognitive Battery (MCCB) Post-Treatment	50.3 T-scores Standard Deviation 11.1	48.6 T-scores Standard Deviation 8.8
MATRICS Consensus Cognitive Battery (MCCB) Follow Up	50.3 T-scores Standard Deviation 11.0	46.3 T-scores Standard Deviation 9.4

SECONDARY outcome

Timeframe: within 1 week prior to initiating intervention; midpoint - on average after 8 weeks of initiation; post-treatment - on average 24 weeks after initiation; after 6 months of no active study intervention

Population: All randomized participants with at least one assessment

The YMRS is an interview style measure asking about hallmark symptoms of mania. Total score ranges from 0 to 60 where higher scores indicate more severe symptoms of mania. Total score ≤12 indicates remission (13-19=minimal symptoms; 20-25=mild mania, 26-37=moderate mania, 38-60=severe mania). Administration time = approximately 10 minutes

Outcome measures

Outcome measures
Measure	Cognitive Remediation n=39 Participants This arm will receive computer-based cognitive remediation treatment 3 times per week for 24 weeks, for a total of 70 hours of treatment BrainWorks: 13 programs targeting cognition in 4 separate domains: Auditory processing, visual processing, social cognition, and executive functioning. Games are imbedded in a format that is engaging and interactive. Animated characters serve as "directors" for each program, explaining the tasks in both verbal and written formats and providing feedback on each trial and overall after each activity. Users move systematically through the programs and can track their progress as the go. Each session includes activities from several different games to maintain interest and train a variety of skills; however, games are presented in the order of domains listed above (i.e. auditory, then visual, then social, and finally executive) to avoid stimulus interference during the training.	Computer Control n=33 Participants Group will receive 70 hours of computer time playing pre-selected computer games administered in a similar format as the Cognitive Remediation condition Computer Control: Sessions will involve generic computer games administered via the game interface "Sporcle." Sporcle is a game site that offers a collection of quiz-type activities available on line. An administrator can track the activity of subjects including when they logged in, which games they played and for how long, and what their accuracy was on each game. We will use a pre-developed game schedule that includes a mix of each type of game in each session, and ensures that subjects are playing the same games in the same order. This format was developed to mirror the treatment condition, as subjects are given a variety of specific games to play at each session.
Young Mania Rating Scale (YMRS) Baseline	5.6 units on a scale Standard Deviation 4.9	4.6 units on a scale Standard Deviation 4.4
Young Mania Rating Scale (YMRS) Midpoint	3.2 units on a scale Standard Deviation 3.4	4.5 units on a scale Standard Deviation 4.6
Young Mania Rating Scale (YMRS) Post-Treatment	8.1 units on a scale Standard Deviation 8.6	4.1 units on a scale Standard Deviation 3.9
Young Mania Rating Scale (YMRS) Follow UP	5.8 units on a scale Standard Deviation 7.2	3.1 units on a scale Standard Deviation 5.4

SECONDARY outcome

Population: All randomized participants with at least one assessment

The MADRS is an interview-style rating scale to assess severity of symptoms of depression. The MADRS consists of 10 items scored 0-6. Total MADRS scores range from 0-60, with higher score indicates more severe depression. Typical clinical cutoff points are: 0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; 34 - severe depression. Administration time = 10 minutes

Outcome measures

Outcome measures
Measure	Cognitive Remediation n=39 Participants This arm will receive computer-based cognitive remediation treatment 3 times per week for 24 weeks, for a total of 70 hours of treatment BrainWorks: 13 programs targeting cognition in 4 separate domains: Auditory processing, visual processing, social cognition, and executive functioning. Games are imbedded in a format that is engaging and interactive. Animated characters serve as "directors" for each program, explaining the tasks in both verbal and written formats and providing feedback on each trial and overall after each activity. Users move systematically through the programs and can track their progress as the go. Each session includes activities from several different games to maintain interest and train a variety of skills; however, games are presented in the order of domains listed above (i.e. auditory, then visual, then social, and finally executive) to avoid stimulus interference during the training.	Computer Control n=33 Participants Group will receive 70 hours of computer time playing pre-selected computer games administered in a similar format as the Cognitive Remediation condition Computer Control: Sessions will involve generic computer games administered via the game interface "Sporcle." Sporcle is a game site that offers a collection of quiz-type activities available on line. An administrator can track the activity of subjects including when they logged in, which games they played and for how long, and what their accuracy was on each game. We will use a pre-developed game schedule that includes a mix of each type of game in each session, and ensures that subjects are playing the same games in the same order. This format was developed to mirror the treatment condition, as subjects are given a variety of specific games to play at each session.
Montgomery-Asberg Depression Rating Scale (MADRS) Baseline	11.8 units on a scale Standard Deviation 7.5	12.1 units on a scale Standard Deviation 7.1
Montgomery-Asberg Depression Rating Scale (MADRS) Midpoint	9.5 units on a scale Standard Deviation 7.1	10.3 units on a scale Standard Deviation 7.7
Montgomery-Asberg Depression Rating Scale (MADRS) Post-Treatment	12.1 units on a scale Standard Deviation 7.0	8.3 units on a scale Standard Deviation 8.6
Montgomery-Asberg Depression Rating Scale (MADRS) Follow Up	11.9 units on a scale Standard Deviation 9.8	12.3 units on a scale Standard Deviation 10.5

SECONDARY outcome

Population: All randomized participants with at least one completed assessment

The PANSS is an interview-administered measure assessing positive and negative symptoms of psychosis, and general psychiatric symptoms. The PANSS consists of 30 total items scored 1-7 (least to most severe). Both Positive and Negative sub scales consist of 7 items each for a total possible score of 49 for each sub scale; the General sub scale consists of 16 items for a total possible score of 112. As the lowest possible score is 1, the lower bound of PANSS total score is 30. Higher scores reflect greater symptom severity. Based on the authors' original publication Kay and colleagues reported mean score in a sample of people with schizophrenia as follows: Positive scale = 18.20 Negative scale = 21.01 General psychopathology = 37.74 Administration = approximately 40 minutes

Outcome measures

Outcome measures
Measure	Cognitive Remediation n=39 Participants This arm will receive computer-based cognitive remediation treatment 3 times per week for 24 weeks, for a total of 70 hours of treatment BrainWorks: 13 programs targeting cognition in 4 separate domains: Auditory processing, visual processing, social cognition, and executive functioning. Games are imbedded in a format that is engaging and interactive. Animated characters serve as "directors" for each program, explaining the tasks in both verbal and written formats and providing feedback on each trial and overall after each activity. Users move systematically through the programs and can track their progress as the go. Each session includes activities from several different games to maintain interest and train a variety of skills; however, games are presented in the order of domains listed above (i.e. auditory, then visual, then social, and finally executive) to avoid stimulus interference during the training.	Computer Control n=33 Participants Group will receive 70 hours of computer time playing pre-selected computer games administered in a similar format as the Cognitive Remediation condition Computer Control: Sessions will involve generic computer games administered via the game interface "Sporcle." Sporcle is a game site that offers a collection of quiz-type activities available on line. An administrator can track the activity of subjects including when they logged in, which games they played and for how long, and what their accuracy was on each game. We will use a pre-developed game schedule that includes a mix of each type of game in each session, and ensures that subjects are playing the same games in the same order. This format was developed to mirror the treatment condition, as subjects are given a variety of specific games to play at each session.
Positive and Negative Syndrome Scale (PANSS) Baseline	47.5 units on a scale Standard Deviation 8.5	45.6 units on a scale Standard Deviation 10.3
Positive and Negative Syndrome Scale (PANSS) Midpoint	44.3 units on a scale Standard Deviation 11.0	44.0 units on a scale Standard Deviation 10.6
Positive and Negative Syndrome Scale (PANSS) Post-Treatment	50.4 units on a scale Standard Deviation 14.3	42.9 units on a scale Standard Deviation 11.2
Positive and Negative Syndrome Scale (PANSS) Follow Up	47.5 units on a scale Standard Deviation 16.7	45.6 units on a scale Standard Deviation 13.2

SECONDARY outcome

Population: All randomized participants with at least one completed assessment

The MCAS is an interview-based assessment that measures functioning in psychiatric patients in multiple domains including social interest and effectiveness, independence in daily living, and instrumental role functioning. The present study uses an abbreviated version of the form consisting of 11 total items scored 1-5, with higher scores reflecting better community functioning. The abbreviated version (Lewandowski et al., 2013) was selected because it assesses community functioning independent of cognition or clinical symptoms, which would represent a confound in the present study. Total possible scores range from 11-55, with higher scores reflecting better community functioning.

Outcome measures

Outcome measures
Measure	Cognitive Remediation n=39 Participants This arm will receive computer-based cognitive remediation treatment 3 times per week for 24 weeks, for a total of 70 hours of treatment BrainWorks: 13 programs targeting cognition in 4 separate domains: Auditory processing, visual processing, social cognition, and executive functioning. Games are imbedded in a format that is engaging and interactive. Animated characters serve as "directors" for each program, explaining the tasks in both verbal and written formats and providing feedback on each trial and overall after each activity. Users move systematically through the programs and can track their progress as the go. Each session includes activities from several different games to maintain interest and train a variety of skills; however, games are presented in the order of domains listed above (i.e. auditory, then visual, then social, and finally executive) to avoid stimulus interference during the training.	Computer Control n=33 Participants Group will receive 70 hours of computer time playing pre-selected computer games administered in a similar format as the Cognitive Remediation condition Computer Control: Sessions will involve generic computer games administered via the game interface "Sporcle." Sporcle is a game site that offers a collection of quiz-type activities available on line. An administrator can track the activity of subjects including when they logged in, which games they played and for how long, and what their accuracy was on each game. We will use a pre-developed game schedule that includes a mix of each type of game in each session, and ensures that subjects are playing the same games in the same order. This format was developed to mirror the treatment condition, as subjects are given a variety of specific games to play at each session.
Multnomah Community Ability Scale (MCAS) Baseline	47.7 T-scores Standard Deviation 4.3	48.3 T-scores Standard Deviation 3.8
Multnomah Community Ability Scale (MCAS) Midpoint	48.7 T-scores Standard Deviation 4.1	49.0 T-scores Standard Deviation 4.4
Multnomah Community Ability Scale (MCAS) Post-Treatment	47.2 T-scores Standard Deviation 4.1	48.7 T-scores Standard Deviation 4.6
Multnomah Community Ability Scale (MCAS) Follow Up	47.7 T-scores Standard Deviation 5.2	47.8 T-scores Standard Deviation 4.7

SECONDARY outcome

Population: All randomized participants with at least one completed assessment

The SOFAS is a 100-point scale similar to the Global Assessment of Functioning designed to evaluate social and occupational functioning not directly influenced by psychological symptom severity. Assessment is based on rater impression and includes a single assigned number. Scores may range from 0-100, with higher scores reflecting better functioning.

Outcome measures

Outcome measures
Measure	Cognitive Remediation n=39 Participants This arm will receive computer-based cognitive remediation treatment 3 times per week for 24 weeks, for a total of 70 hours of treatment BrainWorks: 13 programs targeting cognition in 4 separate domains: Auditory processing, visual processing, social cognition, and executive functioning. Games are imbedded in a format that is engaging and interactive. Animated characters serve as "directors" for each program, explaining the tasks in both verbal and written formats and providing feedback on each trial and overall after each activity. Users move systematically through the programs and can track their progress as the go. Each session includes activities from several different games to maintain interest and train a variety of skills; however, games are presented in the order of domains listed above (i.e. auditory, then visual, then social, and finally executive) to avoid stimulus interference during the training.	Computer Control n=33 Participants Group will receive 70 hours of computer time playing pre-selected computer games administered in a similar format as the Cognitive Remediation condition Computer Control: Sessions will involve generic computer games administered via the game interface "Sporcle." Sporcle is a game site that offers a collection of quiz-type activities available on line. An administrator can track the activity of subjects including when they logged in, which games they played and for how long, and what their accuracy was on each game. We will use a pre-developed game schedule that includes a mix of each type of game in each session, and ensures that subjects are playing the same games in the same order. This format was developed to mirror the treatment condition, as subjects are given a variety of specific games to play at each session.
Social and Occupational Functioning Assessment Scale Baseline	59.4 units on a scale Standard Deviation 12.5	55.9 units on a scale Standard Deviation 13.6
Social and Occupational Functioning Assessment Scale Midpoint	58.1 units on a scale Standard Deviation 11.8	59.2 units on a scale Standard Deviation 14.7
Social and Occupational Functioning Assessment Scale Post-Treatment	58.2 units on a scale Standard Deviation 13.5	62.8 units on a scale Standard Deviation 55.2
Social and Occupational Functioning Assessment Scale Follow Up	55.2 units on a scale Standard Deviation 18.1	62.3 units on a scale Standard Deviation 15.6

OTHER_PRE_SPECIFIED outcome

Timeframe: within 1 week prior to initiating intervention; post-treatment - on average 24 weeks after initiation

resting state, task-based fMRI; Diffusion Tensor Imaging

Outcome measures

Outcome data not reported

Adverse Events

Cognitive Remediation

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Computer Control

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Dr. Kathryn Lewandowski

McLean Hospital/Harvard Medical School

Phone: 617-855-2886

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place