SchizophreniaNCT00923078
Neurophysiological Targets for Cognitive Training in Schizophrenia
A study testing Auditory Cognitive Training and Visual Cognitive Training in people with Schizophrenia, run by VA Office of Research and Development at 1 site in United States.
Trial summary
The purpose of this study is to determine whether computer-based training of auditory and visual processing results in corresponding improvement in brain function in individuals with schizophrenia. Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Schizophrenia
- What is being tested?
- Auditory Cognitive Training and Visual Cognitive Training
- Type of treatment
- Lifestyle or therapy programme
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2010to Oct 2014
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- DSM-IV diagnosis of schizophrenia or schizoaffective disorder
- Age between 18 \& 70
- minimum of 30 days since discharge from last hospitalization
- minimum of 30 days since last change in psychiatric medications
- receiving mental health services
- no housing changes in the past 30 days
Who cannot join
- current diagnosis of alcohol or substance abuse
- history of brain trauma or neurological disease
- chart diagnosis of mental retardation or premorbid intelligence < 70 based on Wechsler Test of Adult Reading (WTAR) full-scale estimated IQ
- auditory or visual impairment that would interfere with study procedures
- a sample of 20 healthy community volunteers was also recruited according to these criteria and tested, without intervention, as a normative reference sample for MMN and P300 measures
Trial locations and contacts
1 site in 1 country.
United States1 site
VA Connecticut Health Care System (West Haven)
West Haven, Connecticut, 06516
About this study
The purpose of this study is to determine whether computer-based training of auditory and visual processing results in corresponding improvement in brain function in individuals with schizophrenia.
Read the detailed description
Schizophrenia is recognized as one of the leading causes of medical disability worldwide, ranked 9th overall by the World Health Organization, and affects more than 2 million Americans per year. There is considerable evidence to suggest that disability status in schizophrenia relates more directly to cognitive Impairment, involving attention, reasoning, and memory, than to characteristic symptoms of psychosis. Accordingly, the evaluation and advancement of interventions designed to restore cognitive function, generally termed cognitive remediation, is of critical importance to our rehabilitation mission. Recent randomized controlled trials of cognitive remediation in schizophrenia have found moderate gains in cognitive function and improved outcomes in important areas of community living. However, despite these encouraging findings, there remains sparse evidence in support of assumptions that (1) cognitive outcomes represent benefits of training-induced adaptive learning, (2) that training effects are specific to method of intervention, or (3) that change in cognitive test performance occurs through restoration of impaired neural circuitry in schizophrenia. This project will begin to address these issues by examining modality-specific effects of computer-based cognitive training on psychophysiological measures of sensory information processing. Training will be administered using two commercially available computer-based software packages, separately targeting auditory and visually-mediated processes using principles of bottom-up perceptual learning. Two psychophysiological paradigms, mismatch negativity (MMN) and P300 generation, will be administered as tests of early visual and auditory processing. MMN and P300 have been studied extensively in human neuroscience as probes of sensory echoic memory and attention engagement to contextually relevant information. Furthermore, reductions in MMN and P300 generation are reliably observed in schizophrenia, follow the course of a progressive neuropathological process, and correlate with severity of cognitive impairment. The specific aims of this study are to determine: (1) whether training selectively influences bottom-up (MMN) or top-down (P300) information processing, (2) whether training effects are modality (auditory vs. visual) specific, (3) whether baseline MMN and P300 predict, or rate-limit, training progress, and (4) whether pre-post change in cognitive test performance is mediated by neural-level change in MMN and P300 generation. Answers to these questions will provide information needed to structure cognitive training for maximum benefit in schizophrenia.
- Conditions
- Schizophrenia
- Being tested
- Auditory Cognitive Training, Visual Cognitive Training
- Keywords
- schizophrenia, cognitive remediation, rehabilitation, electrophysiology, neuropsychology
- Medical subject headings
- Schizophrenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Auditory Cognitive TrainingBehavioural
Also called Brain Fitness by Posit Science
The program entails six computer-based exercises that are designed to be very easy to use and require no computer experience. The exercises are calibrated to individual performance at the onset of training and adapt in difficulty to individual performance, giving constant feedback about progress. Each of the six exercises focuses on a distinct process: (1) auditory processing speed, (2) discriminating sounds, (3) sound precision, (4) sound sequencing, (5) working memory, and (6) narrative memory. Training was administered in a supervised clinical laboratory setting at a frequency of five 60-minute sessions per week over 4 weeks.
Visual Cognitive TrainingBehavioural
Also called Cortex with Insight by Posit Science
The program entails five computer-based exercises that are designed to be very easy to use and require no computer experience. The exercises are calibrated to individual performance at the onset of training and, following our laboratory procedures, calibration testing is repeated every 5th session. Exercises adapt in difficulty to individual performance, giving constant feedback about progress. Each of the five exercises focuses on a distinct process: (1) visual precision, (2) visual processing speed, (3) divided attention, (4) visual working memory, and (5) useful field of view. Training was administered in a supervised clinical laboratory setting at a frequency of five 40-minute sessions per week over 4 weeks.
| Study group | Role | What they receive |
|---|---|---|
| Auditory-Visual Train Order | Experimental | 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness) followed by 4 weeks (20 sessions) of visual cognitive training (Insight) Receives: Behavioral: Auditory Cognitive Training; Behavioral: Visual Cognitive Training |
| Visual-Auditory Train Order | Experimental | 4 weeks (20 sessions) of visual cognitive training (Insight) followed by 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness) Receives: Behavioral: Auditory Cognitive Training; Behavioral: Visual Cognitive Training |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Target Detection (P300 Event-related Potential Amplitude) Change
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.
Measured: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
Auditory Mismatch Negativity (MMN) Amplitude Change
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.
Measured: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
MCCB Cognitive Composite Score Change
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.
Measured: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
Secondary outcomes (4)
Visual Learning (BVMT-R) Change
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.
Measured: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
Verbal Learning (HVLT-R) Change
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.
Measured: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
Visual Working Memory (Spatial Span) Change
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.
Measured: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
Auditory Working Memory (LNS) Change
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.
Measured: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Jun 2009 (estimated)
- Study startNov 2010
- Primary completionOct 2014
- Study completionOct 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for SchizophreniaStudies of the same condition, open and under way.
- More trials run by VA Office of Research and DevelopmentThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- VA Office of Research and Development
- Sponsor type
- US federal agency
- Responsible party
- Sponsor
- Investigators
- Jason K Johannesen, PhD, Principal investigator, VA Connecticut Health Care System (West Haven)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00923078
- Sponsor's protocol ID
- D7008-W
- Status last verified
- Dec 2017
- First submitted
- 17 Jun 2009
- Last updated
- 22 Dec 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Dec 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neurophysiological Targets for Cognitive Training in Schizophrenia
- ClinicalTrials.gov ID
- NCT00923078
- Acronym / sponsor ID
- D7008-W
- Conditions
- Schizophrenia
- Keywords
- schizophrenia, cognitive remediation, rehabilitation, electrophysiology, neuropsychology
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- VA Office of Research and DevelopmentUS federal agency
- Study start
- Nov 2010
- Primary completion
- Oct 2014 (actual)
- Study completion
- Oct 2014 (actual)
- First posted
- 18 Jun 2009 (estimated)
- Results
- Posted 20 Dec 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to determine whether computer-based training of auditory and visual processing results in corresponding improvement in brain function in individuals with schizophrenia.
Detailed description
Schizophrenia is recognized as one of the leading causes of medical disability worldwide, ranked 9th overall by the World Health Organization, and affects more than 2 million Americans per year. There is considerable evidence to suggest that disability status in schizophrenia relates more directly to cognitive Impairment, involving attention, reasoning, and memory, than to characteristic symptoms of psychosis. Accordingly, the evaluation and advancement of interventions designed to restore cognitive function, generally termed cognitive remediation, is of critical importance to our rehabilitation mission. Recent randomized controlled trials of cognitive remediation in schizophrenia have found moderate gains in cognitive function and improved outcomes in important areas of community living. However, despite these encouraging findings, there remains sparse evidence in support of assumptions that (1) cognitive outcomes represent benefits of training-induced adaptive learning, (2) that training effects are specific to method of intervention, or (3) that change in cognitive test performance occurs through restoration of impaired neural circuitry in schizophrenia. This project will begin to address these issues by examining modality-specific effects of computer-based cognitive training on psychophysiological measures of sensory information processing. Training will be administered using two commercially available computer-based software packages, separately targeting auditory and visually-mediated processes using principles of bottom-up perceptual learning. Two psychophysiological paradigms, mismatch negativity (MMN) and P300 generation, will be administered as tests of early visual and auditory processing. MMN and P300 have been studied extensively in human neuroscience as probes of sensory echoic memory and attention engagement to contextually relevant information. Furthermore, reductions in MMN and P300 generation are reliably observed in schizophrenia, follow the course of a progressive neuropathological process, and correlate with severity of cognitive impairment. The specific aims of this study are to determine: (1) whether training selectively influences bottom-up (MMN) or top-down (P300) information processing, (2) whether training effects are modality (auditory vs. visual) specific, (3) whether baseline MMN and P300 predict, or rate-limit, training progress, and (4) whether pre-post change in cognitive test performance is mediated by neural-level change in MMN and P300 generation. Answers to these questions will provide information needed to structure cognitive training for maximum benefit in schizophrenia.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Auditory-Visual Train Order | Experimental | Behavioral: Auditory Cognitive Training, Behavioral: Visual Cognitive Training4 weeks (20 sessions) of auditory cognitive training (Brain Fitness) followed by 4 weeks (20 sessions) of visual cognitive training (Insight) |
| Visual-Auditory Train Order | Experimental | Behavioral: Auditory Cognitive Training, Behavioral: Visual Cognitive Training4 weeks (20 sessions) of visual cognitive training (Insight) followed by 4 weeks (20 sessions) of auditory cognitive training (Brain Fitness) |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- DSM-IV diagnosis of schizophrenia or schizoaffective disorder
- Age between 18 \& 70
- minimum of 30 days since discharge from last hospitalization
- minimum of 30 days since last change in psychiatric medications
- receiving mental health services
Key exclusion criteria (5 listed)
- current diagnosis of alcohol or substance abuse
- history of brain trauma or neurological disease
- chart diagnosis of mental retardation or premorbid intelligence < 70 based on Wechsler Test of Adult Reading (WTAR) full-scale estimated IQ
- auditory or visual impairment that would interfere with study procedures
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Auditory Cognitive TrainingAlso: Brain Fitness by Posit ScienceThe program entails six computer-based exercises that are designed to be very easy to use and require no computer experience. The exercises are calibrated to individual performance at the onset of training and adapt in difficulty to individual performance, giving constant feedback about progress. Each of the six exercises focuses on a distinct process: (1) auditory processing speed, (2) discriminating sounds, (3) sound precision, (4) sound sequencing, (5) working memory, and (6) narrative memory. Training was administered in a supervised clinical laboratory setting at a frequency of five 60-minute sessions per week over 4 weeks. | Behavioural | Auditory-Visual Train Order, Visual-Auditory Train Order |
| Visual Cognitive TrainingAlso: Cortex with Insight by Posit ScienceThe program entails five computer-based exercises that are designed to be very easy to use and require no computer experience. The exercises are calibrated to individual performance at the onset of training and, following our laboratory procedures, calibration testing is repeated every 5th session. Exercises adapt in difficulty to individual performance, giving constant feedback about progress. Each of the five exercises focuses on a distinct process: (1) visual precision, (2) visual processing speed, (3) divided attention, (4) visual working memory, and (5) useful field of view. Training was administered in a supervised clinical laboratory setting at a frequency of five 40-minute sessions per week over 4 weeks. | Behavioural | Auditory-Visual Train Order, Visual-Auditory Train Order |
Primary outcome
Visual Target Detection (P300 Event-related Potential Amplitude) Change
Time frame: 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.
Auditory Mismatch Negativity (MMN) Amplitude Change
Time frame: 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.
MCCB Cognitive Composite Score Change
Time frame: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
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.
4 secondary outcomes
Visual Learning (BVMT-R) Change
Time frame: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
Verbal Learning (HVLT-R) Change
Time frame: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
Visual Working Memory (Spatial Span) Change
Time frame: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
Auditory Working Memory (LNS) Change
Time frame: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Dec 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jason K Johannesen, PhD principal investigator
VA Connecticut Health Care System (West Haven)
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Auditory Cognitive Training and Visual Cognitive Training in people with Schizophrenia, run by VA Office of Research and Development at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Dec 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 20 Dec 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Visual Target Detection (P300 Event-related Potential Amplitude) Change (time frame: Baseline; Post 4 weeks (treatment crossover); Post 8 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Dec 2017.