Trial Outcomes & Findings for Neurophysiological Targets for Cognitive Training in Schizophrenia (NCT NCT00923078)

NCT ID: NCT00923078

Last Updated: 2017-12-22

Results Overview

Visual P300 was measured in a 3-stimulus target detection task with target stimuli (10%; large circle) presented in pseudo random order amidst a series of novel (10%; fractal), and standard (80%; small circle) images on a 24" LCD monitor at 100cm viewing distance. Subjects are instructed to press a reaction time button with the preferred hand to Targets only, giving equal importance to speed and accuracy. Primary analysis are based on Target "P300b" identified as the most positive amplitude deflection within the window of 250-550ms post stimulus at posterior midline electrode Pz. The P300b component is thought to reflect cognitive processes involved in memory updating and decision making. P300 reported as difference scores from baseline with negative values indicating increased P300.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 60 participants
• Primary outcome timeframe: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
• Results posted on: 2017-12-22

Participant Flow

Healthy comparison subjects completed a single assessment at baseline and did not receive intervention or follow-up testing.

Participant milestones

Measure	Auditory Then Visual Cognitive Training 20 individuals with schizophrenia randomized to 4 weeks (20 sessions) of auditory training (Brain Fitness) followed by 4 weeks (20 sessions) of visual training (Insight).	Visual Then Auditory Cognitive Training 20 individuals with schizophrenia randomized to 4 weeks (20 sessions) of visual training (Insight) followed by 4 weeks (20 sessions) of auditory training (Brain Fitness).	Healthy Comparison A sample healthy community volunteers participated in a single test session to provide normative comparison data on neurophysiological (P300, MMN) outcome measures
First Intervention (Weeks 1-4) STARTED	20	20	20
First Intervention (Weeks 1-4) COMPLETED	19	19	0
First Intervention (Weeks 1-4) NOT COMPLETED	1	1	20
Second Intervention (Weeks 5-8) STARTED	19	19	0
Second Intervention (Weeks 5-8) COMPLETED	19	19	0
Second Intervention (Weeks 5-8) NOT COMPLETED	0	0	0

Reasons for withdrawal

Measure	Auditory Then Visual Cognitive Training 20 individuals with schizophrenia randomized to 4 weeks (20 sessions) of auditory training (Brain Fitness) followed by 4 weeks (20 sessions) of visual training (Insight).	Visual Then Auditory Cognitive Training 20 individuals with schizophrenia randomized to 4 weeks (20 sessions) of visual training (Insight) followed by 4 weeks (20 sessions) of auditory training (Brain Fitness).	Healthy Comparison A sample healthy community volunteers participated in a single test session to provide normative comparison data on neurophysiological (P300, MMN) outcome measures
First Intervention (Weeks 1-4) Withdrawal by Subject	1	1	0
First Intervention (Weeks 1-4) No intervention per protocol	0	0	20

Baseline Characteristics

The PANSS is a schizophrenia symptom severity measure, ratings not obtained in healthy community sample

Baseline characteristics by cohort

Measure	Auditory-Visual Train Order n=20 Participants N = 20 participants with schizophrenia randomized to 4 weeks (20 sessions) of auditory training (Brain Fitness) followed by 4 weeks (20 sessions) of visual training (Insight)	Visual-Auditory Train Order n=20 Participants N = 20 participants with schizophrenia randomized to 4 weeks (20 sessions) of visual training (Insight) followed by 4 weeks (20 sessions) of auditory training (Brain Fitness)	Healthy Comparison n=20 Participants N = 20 healthy community volunteers participated in a single test session to provide normative comparison data	Total n=60 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=20 Participants	0 Participants n=20 Participants	0 Participants n=20 Participants	0 Participants n=60 Participants
Age, Categorical Between 18 and 65 years	19 Participants n=20 Participants	19 Participants n=20 Participants	20 Participants n=20 Participants	58 Participants n=60 Participants
Age, Categorical >=65 years	1 Participants n=20 Participants	1 Participants n=20 Participants	0 Participants n=20 Participants	2 Participants n=60 Participants
Age, Continuous	45.65 years STANDARD_DEVIATION 12.26 • n=20 Participants	46.55 years STANDARD_DEVIATION 12.85 • n=20 Participants	39.15 years STANDARD_DEVIATION 13.39 • n=20 Participants	43.78 years STANDARD_DEVIATION 13.05 • n=60 Participants
Sex: Female, Male Female	7 Participants n=20 Participants	10 Participants n=20 Participants	9 Participants n=20 Participants	26 Participants n=60 Participants
Sex: Female, Male Male	13 Participants n=20 Participants	10 Participants n=20 Participants	11 Participants n=20 Participants	34 Participants n=60 Participants
Region of Enrollment United States	20 participants n=20 Participants	20 participants n=20 Participants	20 participants n=20 Participants	60 participants n=60 Participants
IQ	95.20 units on a scale STANDARD_DEVIATION 14.83 • n=20 Participants	87.70 units on a scale STANDARD_DEVIATION 12.32 • n=20 Participants	103.26 units on a scale STANDARD_DEVIATION 13.86 • n=20 Participants	95.25 units on a scale STANDARD_DEVIATION 14.90 • n=60 Participants
Cognitive Composite Score	36.35 t-score STANDARD_DEVIATION 12.86 • n=20 Participants	30.40 t-score STANDARD_DEVIATION 12.87 • n=20 Participants	45.95 t-score STANDARD_DEVIATION 13.70 • n=20 Participants	37.57 t-score STANDARD_DEVIATION 14.45 • n=60 Participants
Positive and Negative Syndrome Scale (PANSS)	56.8 units on a scale STANDARD_DEVIATION 12.89 • n=20 Participants • The PANSS is a schizophrenia symptom severity measure, ratings not obtained in healthy community sample	56.8 units on a scale STANDARD_DEVIATION 13.94 • n=20 Participants • The PANSS is a schizophrenia symptom severity measure, ratings not obtained in healthy community sample	—	56.8 units on a scale STANDARD_DEVIATION 13.25 • n=40 Participants • The PANSS is a schizophrenia symptom severity measure, ratings not obtained in healthy community sample

PRIMARY outcome

Timeframe: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks

Visual P300 was measured in a 3-stimulus target detection task with target stimuli (10%; large circle) presented in pseudo random order amidst a series of novel (10%; fractal), and standard (80%; small circle) images on a 24" LCD monitor at 100cm viewing distance. Subjects are instructed to press a reaction time button with the preferred hand to Targets only, giving equal importance to speed and accuracy. Primary analysis are based on Target "P300b" identified as the most positive amplitude deflection within the window of 250-550ms post stimulus at posterior midline electrode Pz. The P300b component is thought to reflect cognitive processes involved in memory updating and decision making. P300 reported as difference scores from baseline with negative values indicating increased P300.

Outcome measures

Measure	Auditory Cognitive Training n=38 Participants 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness) completed either before or following 4 weeks (20 sessions) of visual cognitive training (Insight)	Visual Cognitive Training n=38 Participants 4 weeks (20 sessions) of visual cognitive training (Insight) completed either before or following 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness)
Visual Target Detection (P300 Event-related Potential Amplitude) Change	2.20 microvolts (uV) Standard Error 1.02	-0.72 microvolts (uV) Standard Error 1.02

PRIMARY outcome

Timeframe: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks

Auditory MMN is a fronto-central, mid-latency, potential generated by the auditory cortex in response to deviation in a repetitive stimulus sequence. MMN was assessed using a 3-deviant paradigm in which a series of standard tones (633 Hz, 50ms duration,90%) is interrupted by deviants (10%) that differ either by (1) pitch (1000Hz, 50ms), (2) duration (633 Hz, 100ms), or (3) both (1000Hz, 100ms). MMN was tested concurrently with Visual P300 using a combined task in which subjects were instructed to ignore the auditory stimuli and focus on the visual stimuli. MMN is scored by subtracting each deviant ERP waveform from the standard waveform and measuring the most negative deflection in a window of 50 to 265ms post-stimulus from the resulting difference wave. Primary analysis is based on the combined deviant condition scored at the frontal midline (Fz) electrode site. MMN reported as difference scores from baseline with positive values indicating increased MMN.

Outcome measures

Measure	Auditory Cognitive Training n=38 Participants 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness) completed either before or following 4 weeks (20 sessions) of visual cognitive training (Insight)	Visual Cognitive Training n=38 Participants 4 weeks (20 sessions) of visual cognitive training (Insight) completed either before or following 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness)
Auditory Mismatch Negativity (MMN) Amplitude Change	0.67 microvolts (uV) Standard Error 0.29	0.51 microvolts (uV) Standard Error 0.29

PRIMARY outcome

Timeframe: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks

Population: Of N=40 randomized, analysis was based on 38 who completed intervention and post-testing. Across conditions, participants completed, on average, 14.61 hrs of training in Period 1 (12.53 visual, 16.70 auditory) and 14.41 hrs in Period 2 (13.00 visual, 15.92 auditory)

The Cognitive Composite score is derived from the MATRICS Consensus Cognitive Battery (MCCB). The MCCB consists of 10 tests and provides standard scores for each according to seven cognitive domains: (1) speed of processing, (2) attention/vigilance, (3) working memory (verbal and visual), (4) verbal learning, (5) visual learning, (6) reasoning and problem solving, and (7) social cognition. The primary dependent measures derived from the MCCB for purpose of this study is the cognitive composite score, computed as the average of standard (t-scores) scores from each domain excluding social cognition. MCCB Composite reported as difference scores from baseline with negative values indicating higher test performance.

Outcome measures

Measure	Auditory Cognitive Training n=38 Participants 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness) completed either before or following 4 weeks (20 sessions) of visual cognitive training (Insight)	Visual Cognitive Training n=38 Participants 4 weeks (20 sessions) of visual cognitive training (Insight) completed either before or following 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness)
MCCB Cognitive Composite Score Change	-2.03 t-score Standard Error 0.75	-2.45 t-score Standard Error 0.75

SECONDARY outcome

Timeframe: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks

The visual learning domain of the MCCB is assessed using the Brief Visuospatial Memory Test-Revised (BVMT-R). In three Learning Trials, the respondent views a stimulus display for 10 seconds and is then asked to draw as many of the figures as possible in their correct location on a page in the response booklet. Scores represent overall accuracy across the three trials, with higher scores indicating better learning. Analysis is based on age- and gender-corrected t-scores. BVMT-R reported as difference scores from baseline with negative values indicating higher test performance.

Outcome measures

Measure	Auditory Cognitive Training n=38 Participants 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness) completed either before or following 4 weeks (20 sessions) of visual cognitive training (Insight)	Visual Cognitive Training n=38 Participants 4 weeks (20 sessions) of visual cognitive training (Insight) completed either before or following 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness)
Visual Learning (BVMT-R) Change	-2.92 t-score Standard Error 1.55	-3.24 t-score Standard Error 1.55

SECONDARY outcome

Timeframe: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks

The verbal learning domain of the MCCB is assessed using the Hopkins Verbal Learning Test-Revised (HVLT-R). In three Learning Trials, the respondent listens to a 12-item word list read by an examiner and is then asked to recall as many of the words as possible from memory. Scores represent overall accuracy across the three trials, with higher scores indicating better learning. Analysis is based on age- and gender-corrected t-scores. HVLT-R reported as difference scores from baseline with negative values indicating higher test performance.

Outcome measures

Measure	Auditory Cognitive Training n=38 Participants 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness) completed either before or following 4 weeks (20 sessions) of visual cognitive training (Insight)	Visual Cognitive Training n=38 Participants 4 weeks (20 sessions) of visual cognitive training (Insight) completed either before or following 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness)
Verbal Learning (HVLT-R) Change	0.62 t-score Standard Error 1.04	0.03 t-score Standard Error 1.03

SECONDARY outcome

Timeframe: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks

Visual working memory is assessed in the MCCB using the Spatial Span task of the Wechsler Memory Scales-III. Using a board on which 10 cubes are irregularly spaced, the examiner taps patterns of increasing length. The respondent is asked to follow by tapping the pattern in the same or reverse sequence. Scores represent total accuracy combined over forward and reverse span conditions. Analysis is based on age- and gender-corrected t-scores. Spatial Span reported as difference scores from baseline with negative values indicating higher test performance.

Outcome measures

Measure	Auditory Cognitive Training n=38 Participants 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness) completed either before or following 4 weeks (20 sessions) of visual cognitive training (Insight)	Visual Cognitive Training n=38 Participants 4 weeks (20 sessions) of visual cognitive training (Insight) completed either before or following 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness)
Visual Working Memory (Spatial Span) Change	-0.60 t-score Standard Error 1.27	-0.92 t-score Standard Error 1.27

SECONDARY outcome

Timeframe: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks

Auditory working memory is assessed in the MCCB using the Letter-Number Sequencing (LNS) task. LNS is an orally administered test in which and examiner reads strings of numbers and letters, of increasing length over trials, and the respondent mentally reorders the string and reports back to the examiner verbally. Scores represent total number of accurate trials. Analysis is based on age- and gender-corrected t-scores. LNS reported as difference scores from baseline with negative values indicating higher test performance.

Outcome measures

Measure	Auditory Cognitive Training n=38 Participants 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness) completed either before or following 4 weeks (20 sessions) of visual cognitive training (Insight)	Visual Cognitive Training n=38 Participants 4 weeks (20 sessions) of visual cognitive training (Insight) completed either before or following 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness)
Auditory Working Memory (LNS) Change	-1.10 t-score Standard Error 0.98	-1.47 t-score Standard Error 0.97

Adverse Events

Auditory Cognitive Training

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Visual Cognitive Training

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Healthy Comparison

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 Jason K. Johannesen

VA Connecticut Healthcare System

Phone: 2039325711

Email: jason.johannesen@va.gov

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place