- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01891721
Evaluating Two Types of Cognitive Training in Veterans With Schizophrenia
Study Overview
Status
Conditions
Detailed Description
Schizophrenia is a disorder that affects both higher-level neurocognitive operations (e.g., verbal memory, executive functioning) and lower-level perceptual processes (e.g., auditory processing). These deficits contribute to the poor community outcome and severe functional disability seen in patients. Effectively treating the cognitive dysfunction associated with this illness is important to achieve improvements in daily functioning. Recent meta-analytic studies report that cognitive training in schizophrenia has a moderate effect-size impact on cognitive functioning and a lower impact on daily functioning. However, most training interventions for schizophrenia have only targeted higher-order cognitive processes. A few recent interventions have targeted basic perceptual processing and shown that auditory and visual perceptual abilities can be trained and improved in patients with schizophrenia. These findings suggest that basic perceptual processing may be an ideal target for intervention. At this point, it is still unclear whether a neuroplasticity-based, bottom-up intervention is more effective than an intervention that targets top-down functions like attention, working memory, and executive functioning.
This clinical trial will contrast a bottom-up intervention targeting basic auditory processes and a top-down intervention targeting higher-order cognitive functions, compared with a control condition, in Veterans with schizophrenia. These interventions will be assessed by their effects on representative measures from three outcome domains: 1) neurocognition, 2) electroencephalography (EEG), and 3) functional capacity. Participants will be randomly assigned to the bottom-up auditory training, top-down cognitive training, or control treatment (commercial computer games). All treatments will be administered three times a week (1 hour each) for 12 weeks. A comprehensive battery of cognitive, electrophysiological, and functional measures will be administered at baseline, 6 weeks, and at completion of treatment. The investigators will enroll 120 Veterans with schizophrenia or schizoaffective disorder across the 5 years of the study.
This study will determine which training approach leads to the largest magnitude of improvement in neurocognition, functional capacity, and neural functioning measured with EEG. Moreover, it will shed light on the neural mechanisms underlying the response to training. By determining whether it is more beneficial to treat lower-level perceptual processes or higher-level cognitive functions, the results of this project will inform future recovery-based cognitive remediation interventions for Veterans with schizophrenia.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
California
-
Los Angeles, California, United States, 90073
- Local Board and Care Facilities
-
West Los Angeles, California, United States, 90073
- VA Greater Los Angeles Healthcare System, West Los Angeles, CA
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Veterans with a Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) diagnosis of schizophrenia or schizoaffective disorder
- Between 25 and 65 years of age
- Estimated premorbid inteIligence quotient (IQ) > 70 (based on reading ability)
- Understand spoken English sufficiently to comprehend the consent form
- Clinically stable (i.e., no inpatient hospitalization in the 3 months, no changes in psychiatric medications in the 6 weeks, and no changes in housing in the 2 months, prior to enrollment)
Exclusion Criteria:
- Documented history of mental retardation or severe learning disability
- Clinically significant neurological disease as determined by medical history (e.g., epilepsy, stroke)
- History of serious head injury with loss of consciousness greater than 1 hour and concomitant neuropsychological sequelae
- Meeting DSM-IV criteria for drug or alcohol dependence during the 6 months, or abuse during the month preceding study enrollment
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Triple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Specific Perceptual Training - Brain Fitness Program (BFP)
In each session, participants will work on 4 of the 6 BFP exercises (15 min per exercise).
Duration of training is 1 hour per day, 3 days per week, for 12 weeks, for a total of 36 hours.
|
This computerized "bottom-up" cognitive intervention is designed to improve the speed and accuracy of auditory information processing through increasingly more difficult stimulus recognition, discrimination, sequencing, and memory tasks under conditions of close attentional control, high reward, and novelty.
BFP consists of 6 exercises.
Stimuli across the exercises are chosen such that they span the acoustic and organizational structure of speech, from very simple acoustic stimuli and tasks to complex manipulations of continuous speech.
The exercises adaptively progress based on the subject's individual performance during a training session and become more challenging as the subject's abilities improve.
Participants will work with 4 of the 6 exercises (15 min per exercise) in each session.
|
Experimental: Broad Cognitive Training - Cognitive Package (Cogpack)
In each session, participants will work on a different subset of 4 to 6 Cogpack exercises.
Duration of training is 1 hour per day, 3 days per week, for 12 weeks, for a total of 36 hours.
|
This computerized "top-down" cognitive intervention is designed to provide training across a broad range of cognitive functions.
Cogpack consists of domain-specific exercises aimed at training specific cognitive areas (attention, working memory, verbal and visual memory, executive functioning, reasoning, language) and non-domain-specific exercises that require the use of several functions at a time.
Cogpack includes low-level cognitive exercises (i.e., scanning, hand-eye coordination, and psychomotor speed) that will not be included in this protocol to better separate bottom-up from top-down training interventions.
There will be a total of 34 exercises and variants of the same exercises with different levels of difficulty.
In each session, participants will work on a different subset of 4 to 6 exercises.
|
Active Comparator: Control Treatment - Commercial Computer Games (Sporcle)
In each session, participants will play between 8 and 16 games (1 to 15 min per game).
Duration of training is 1 hour per day, 3 days per week, for 12 weeks, for a total of 36 hours.
|
Sporcle computer games will be used as a "placebo" treatment to control for the effects of computer exposure, contact with research personnel, time spent being cognitively active, and financial compensation for participation.
The games cover trivia-type questions about geography, entertainment, science, history, literature, sports, movies, etc. Subjects will receive the same amount of attention from staff members and the same monetary reinforcements as participants in the experimental treatment groups.
They will also complete 3 hours of "training" per week over 12 weeks, for a total of 36 hours.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Neurocognition
Time Frame: Within one week of training completion
|
The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) was used to assess basic cognition.
It includes tests representing 6 separable cognitive domains.
The MCCB composite score (average of 6 domain t-scores) served as the primary cognitive outcome measure.
Minimum and maximum values are 20 and 68.
Higher scores mean a better outcome.
|
Within one week of training completion
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Electroencephalography (EEG)
Time Frame: After 6 weeks of training and within one week of training completion
|
A Mismatch Negativity (MMN) Paradigm was used to assess basic auditory processing.
MMN amplitude was measured as the mean voltage in the 145-200 ms latency range at pooled frontocentral electodes.
Minimum and maximum values are -8 and +2 microvolts.
More negative scores mean a better outcome.
|
After 6 weeks of training and within one week of training completion
|
Functional Capacity
Time Frame: Within one week of training completion
|
The University of California San Diego (UCSD) Performance-based Skills Assessment (UPSA) was used to assess functional capacity.
The UPSA total score served as a secondary functional outcome measure.
Minimum and maximum values are 40 and 100.
Higher scores mean a better outcome.
|
Within one week of training completion
|
Collaborators and Investigators
Investigators
- Principal Investigator: Carol Jahchan, PhD, VA Greater Los Angeles Healthcare System, West Los Angeles, CA
Publications and helpful links
General Publications
- Green MF, Kern RS, Braff DL, Mintz J. Neurocognitive deficits and functional outcome in schizophrenia: are we measuring the "right stuff"? Schizophr Bull. 2000;26(1):119-36. doi: 10.1093/oxfordjournals.schbul.a033430.
- Fisher M, Holland C, Merzenich MM, Vinogradov S. Using neuroplasticity-based auditory training to improve verbal memory in schizophrenia. Am J Psychiatry. 2009 Jul;166(7):805-11. doi: 10.1176/appi.ajp.2009.08050757. Epub 2009 May 15.
- Medalia A, Choi J. Cognitive remediation in schizophrenia. Neuropsychol Rev. 2009 Sep;19(3):353-64. doi: 10.1007/s11065-009-9097-y. Epub 2009 May 15.
- Adcock RA, Dale C, Fisher M, Aldebot S, Genevsky A, Simpson GV, Nagarajan S, Vinogradov S. When top-down meets bottom-up: auditory training enhances verbal memory in schizophrenia. Schizophr Bull. 2009 Nov;35(6):1132-41. doi: 10.1093/schbul/sbp068. Epub 2009 Sep 10.
- Popov T, Jordanov T, Rockstroh B, Elbert T, Merzenich MM, Miller GA. Specific cognitive training normalizes auditory sensory gating in schizophrenia: a randomized trial. Biol Psychiatry. 2011 Mar 1;69(5):465-71. doi: 10.1016/j.biopsych.2010.09.028. Epub 2010 Nov 18.
- Light GA, Braff DL. Mismatch negativity deficits are associated with poor functioning in schizophrenia patients. Arch Gen Psychiatry. 2005 Feb;62(2):127-36. doi: 10.1001/archpsyc.62.2.127.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- MHBB-015-12F
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Schizophrenia
-
Organon and CoCompletedSchizophrenia, Paranoid | Schizophrenia, Disorganized | Schizophrenia, Undifferentiated
-
Organon and CoCompletedSchizophrenia, Paranoid | Schizophrenia, Disorganized | Schizophrenia, Undifferentiated
-
Bradley LegaRecruiting
-
All India Institute of Medical Sciences, BhubaneswarRecruitingTreatment Resistant SchizophreniaIndia
-
King's College LondonSouth London and Maudsley NHS Foundation TrustRecruitingTreatment-resistant Schizophrenia | Healthy Controls | Treatment-responsive SchizophreniaUnited Kingdom
-
University of Sao PauloUnknownRefractory Schizophrenia | Super Refractory SchizophreniaBrazil
-
Rakitzi, StavroulaActive, not recruiting
-
Peking UniversityNot yet recruitingTreatment-resistant Schizophrenia
-
Ohio State UniversityRecruitingTreatment-resistant SchizophreniaUnited States
-
University Hospital, BrestRecruitingSchizophrenia | Schizophrenia Prodromal | Schizophrenia, ChildhoodFrance
Clinical Trials on Brain Fitness Program (BFP)
-
NYU Langone HealthCompletedBreast CancerUnited States
-
University of KonstanzGerman Research FoundationCompleted
-
NYU Langone HealthCompletedTraumatic Brain Injury | Vascular Accident, BrainUnited States
-
Washington University School of MedicineFederal Emergency Management AgencyCompleted
-
Posit Science CorporationCompleted
-
Posit Science CorporationMayo Clinic; University of Southern CaliforniaCompleted
-
Posit Science CorporationCompleted
-
University of CalgaryNational Alliance for Research on Schizophrenia and DepressionCompletedProdromal Schizophrenia
-
University of ManitobaAGE-WELL NCE Inc.Completed
-
University of ManitobaUnknown