Ignite Creation Date:
2024-05-05 @ 5:30 PM
Last Modification Date:
2024-10-26 @ 9:32 AM
Study NCT ID:
NCT00472862
Status:
COMPLETED
Last Update Posted:
2015-04-15
First Post:
2007-05-11
Brief Title:
Neurocognitive Training Integrated in OPUS Treatment Versus OPUS Treatment-as-usual
Sponsor:
Neurocom
Organization:
Neurocom
Study Overview
Official Title:
NEUROCOM Cognitive Training for Patients With First Episode Schizophrenia
Status:
COMPLETED
Status Verified Date:
2015-04
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
NEUROCOM
Brief Summary:
The study examines the effect of cognitive training on cognitive functioning and everyday competencies of patients with schizophrenia
120 patients are expected to be included in this randomized controlled trial running at two sites in Denmark starting January 2007 The effect of a 16-week manualized program of cognitive training integrated in a comprehensive psychosocial treatment OPUS for first-episode schizophrenia patients is compared with the effect of standard treatment OPUS A six month follow-up assessment is conducted to investigate a possible long-term learning effect of cognitive training
Blinded assessments include the MATRICS Consensus Cognitive Battery and a co-primary outcome measure of cognitive improvement A translated version of the UCSD Performance-based Skills Assessment UPSA adjusted to a Danish context
The cognitive training consists of four modules focusing on the domain of attention executive functioning learning and memory Module 1 and 2 are based on computer-assisted training tasks and the following modules focus on more practical everyday tasks and calendar training Cognitive training takes place twice a week and every other week the patient and trainer engage in a dialogue on the patients cognitive difficulties motivational goals and hisher progress in competence level
The use of errorless learning principles scaffolding and attentional externalisation aims at improving the patients performance on cognitive and everyday tasks by learning to apply compensation techniques as well as limiting dysfunctional uses of available cognitive ressources ie excessive self-focus rumination
The study will provide MATRICS Consensus Cognitive Battery results from a relatively large Danish sample of first-episode schizophrenia and contribute with valuable normative data on the UPSA
It is hypothesized that cognitive training integrated in OPUS treatment enhances both cognitive and everyday competence of patients more than OPUS treatment alone Expectations are that cognitive training will demonstrate a small to moderate effect on cognitive functioning and a moderate effect on everyday functioning as measured with the UPSA Moreover patients allocated to cognitive training are expected to show an improvement in self-esteem
120 patients are expected to be included in this randomized controlled trial running at two sites in Denmark starting January 2007 The effect of a 16-week manualized program of cognitive training integrated in a comprehensive psychosocial treatment OPUS for first-episode schizophrenia patients is compared with the effect of standard treatment OPUS A six month follow-up assessment is conducted to investigate a possible long-term learning effect of cognitive training
Blinded assessments include the MATRICS Consensus Cognitive Battery and a co-primary outcome measure of cognitive improvement A translated version of the UCSD Performance-based Skills Assessment UPSA adjusted to a Danish context
The cognitive training consists of four modules focusing on the domain of attention executive functioning learning and memory Module 1 and 2 are based on computer-assisted training tasks and the following modules focus on more practical everyday tasks and calendar training Cognitive training takes place twice a week and every other week the patient and trainer engage in a dialogue on the patients cognitive difficulties motivational goals and hisher progress in competence level
The use of errorless learning principles scaffolding and attentional externalisation aims at improving the patients performance on cognitive and everyday tasks by learning to apply compensation techniques as well as limiting dysfunctional uses of available cognitive ressources ie excessive self-focus rumination
The study will provide MATRICS Consensus Cognitive Battery results from a relatively large Danish sample of first-episode schizophrenia and contribute with valuable normative data on the UPSA
It is hypothesized that cognitive training integrated in OPUS treatment enhances both cognitive and everyday competence of patients more than OPUS treatment alone Expectations are that cognitive training will demonstrate a small to moderate effect on cognitive functioning and a moderate effect on everyday functioning as measured with the UPSA Moreover patients allocated to cognitive training are expected to show an improvement in self-esteem
Detailed Description:
Neurocognition and competence in schizophrenia A randomized controlled trial of cognitive training CT integrated in OPUS treatment versus OPUS treatment-as-usual
The presence of cognitive deficits in schizophrenia It is a well-established fact that cognitive deficits play a major role in functional outcome in schizophrenia Keefe et al 2006 Gold 2004 Up to 85 patients demonstrate cognitive dysfunctions in the range of 1½-2 SD below norm Fagerlund 2004 Corrigan Penn 2001 Heinrichs Zankanis 1998 Cognitive dysfunctions associated with schizophrenia involve attention information processing memory and executive functions leading to difficulties in learning and poor problem solving abilities
Evidence for the effect of rehabilitation on everyday competencies In spite of the severely debilitating cognitive dysfunctions a relatively large number of patients have shown themselves capable of acquiring new abilities eg Kern et al 2005 Sartory et al 2005 Ueland Rund 2004 Krabbendam Aleman 2003 Pilling et al 2002 Harvey Sharma 2001 Tsang Pearson 2001 Danion et al 2001 Bell et al 2003 Wykes et al 1999 2003 Research has shown that training in symptom handling social proficiency training and supportive provisions in occupational relations apparently can help patients with schizophrenia to function in their daily lives learn solving concrete practical and social tasks and manage relatively independently These improvements enhance self-esteem
Effect studies of cognitive rehabilitation A Cochrane review done by Hayes McGrath 2000 include three small randomized controlled trials and fails to provide conclusive data on evidence for or against cognitive training as a treatment for schizophrenia
Krabbendam Alemans review 2003 of 12 controlled studies finds a weighted mean effect size Cohens d of 045 with 95 CI 026-064 which indicates a small to moderate effect of cognitive training CT for patients with schizophrenia
In Twamley et als review 2003 of 17 randomised controlled studies of CT a weighted mean effect size was calculated across studies The weighted mean effect sizes Cohens d were 032 in improvement in cognitive performance 026 in reduction of symptom severity and 051 in the domain of everyday functioning The review authors recommend longitudinal designs as well as the inclusion of real-life outcome measures in future trials
Many studies of CT have been underpowered small sample sizes which limits the conclusions that can be drawn from results of improvement Ueland Rund 2005 The variability of outcome measures used also complicates interpretation of findings thus a consensus battery MATRICS of outcome measures has been suggested for future studies Silverstein Wilkniss 2004 and Bellack 2004 note that the results of cognitive rehabilitation generally fail to secure the ecological validity wherefore CT ought to be integrated in a broader psychosocial programme of intervention for schizophrenia Other shortcomings in earlier studies include short-term programmes lacking sufficient long-sighted follow-up examinations as well as experimental designs lacking consideration of individual abilities and involvement A recent review of cognitive rehabilitation Velligan et al 2006 underscores the importance of addressing motivation as a primary target
Hogarty et als 2004 promising results from a randomised controlled trial N121 of computer-assisted CT also highlight the importance of examining to what extent the control condition psychosocial treatment improve cognitive functioning Broadly viewed there is sufficient evidence that the combination of CT and psychosocial treatment rather than individually appearing initiatives have the greatest potential for promoting treatment outcome Bell et al 2003
There is a need for a well-organised and sufficiently large randomised clinical trial of the effect of integrated CT and psychosocial rehabilitation In order to examine to what extent CT improves the psychosocial rehabilitation and facilitates new learning one must identify and compare improvements on the level of neuropsychological performance as well as the level of everyday competencies Reeder et al 2006 Buchanan et al 2005 McKibbin et al 2004 The present trial employs a prospective design of 16 weeks with a following follow-up 10 months after inclusion and seeks in the CT to secure an individual adaptation and motivation trough continuous evaluations and level adjustments between patient and trainer
Objectives
1 Primary hypothesis The effect of a 16-weeks programme of computer-based CT integrated in OPUS treatment on the patients competencies in daily life is superior to standard OPUS treatment Primary response variable Total score on UPSA-B Patterson et al 2001 Danish version
2 Secondary hypothesis The effect of a 16-weeks programme CT integrated in OPUS treatment on patients cognitive functioning is superior to standard OPUS treatment Response variables Scores on MATRICS Consensus Cognitive Battery MCCB Trailmaking B and WCST-64 computerized version
3 Tertiary hypothesis The effect of a 16-weeks programme of computer-based CT integrated in OPUS treatment is superior to standard OPUS treatment in terms of patients association with the labour market general health and self-esteem Response variables Occupational status and general functioning measures and Rosenbergs Self-Esteem Scale Rosenberg 1989
Furthermore we want to examine the association between first episode patients cognitive function level and competencies in daily life can be divided in primary and secondary objectives
Blinding The instructor for CT will make a call with participants data to CTU and thereafter inform the patients which intervention programme he or she has been allocated to The study is not blinded in regard to patients cognitive trainers and therapists The blinding applies raters engaged with the outcome evaluation In the follow-up the patient is instructed in advance not to reveal what type of treatment they have received By registering which type of intervention the independent assessors of outcome believe the patient to be receiving it will be evaluated if blinding succeeded The randomised intervention allocation is concealed until the statistical analyses of resulting data have been completed
Participants Patients are recruited from OPUS which is implemented as a standard treatment programme for young adults with firstepisode psychosis in Copenhagen and Århus The staff in OPUS recruit patients to the project The independent assessors interview referred patients and evaluate the following in- and exclusion criteria
Inclusion criteria 1 between 18 and 35 years of age 2 first episode psychosis within F2 spectrum or schizotypal disorder in ICD 10 - post-acute phase of illness 3 sufficient comprehension of Danish 4 written informed consent
Exclusion criteria
1 rejection of participation 2 organic disorder 3 noticeable misuse of psychoactive drugs
Control intervention group All patients receive the treatment usually provided in OPUS
Standard treatment in OPUS consists of affiliation with a primary contact person involvement of family possibility of psychoeducation and social skills training described in details at httpwwwpsykiatriaaadkcent_enhopushtm and wwwopus-kbhdk Depending on individual needs patients are offered to take part in group therapy either social skills training SST or cognitive-behavioral therapy CBT Participation in SST or CBT might be beneficial for both cognition and everyday skills To ensure comparability between the patients allocated to experimental intervention CT and the patients allocated to standard OPUS treatment we stratify patients according to group therapy SSTCBT yesno
Patients randomized to the control group will receive treatment as usual as described above
Experimental intervention A pilot study in OPUS Århus has led to the completion of a manual for a 16-week CT programme for patients with schizophrenia Christensen Olsen 2006
One hour twice a week in 16 weeks patients engage in computer-assisted CT plus one competence dialog every other week Training consists of four modules the first three modules cover the areas of attention memory and executive functions and the last module focus on the cognitive area and related tasks that the individual patient need or prefer to work more on Thus the content of module 4 is based on both the patients and the trainers judgement
Training contains exercises of simple attention attention span and vigilance planning problem solving stimulus-bind and perseveration tendency interaction-based training of working memory and verbal and visual long-term memory The CT approach is oriented towards teaching of compensatory strategies but simple repetition of non-social cognitive tasks on a gradually increasing level of difficulty is also part of the CT program By 90 correct task-completion the level is increased
Module 1 and 2 are based on computertasks COGNIsoft whereas the following modules 3 and 4 include practical everyday tasks In their review Twamley Jeste and Bellack 2003 stress the importance of directly targeting everyday functioning of the patient Thus calendartraining is a vital part of this intervention a way of addressing common difficulties of memory and planning ability Calendartraining and competence dialogues both support environmental adaptation and transference of learning
Training relies on errorless learning principles scaffolding repetition and strategy-learning as recommended by Wykes van der Gaag 1999 Positive reinforcement modelling and verbal instructions are widely used Trainers describe the structure and explain the purpose of training exercises at the beginning of every session to provide a consistent learning environment
Assessments All assessments except Present State Examination-interview PSE clinical version and premorbid IQ DART Danish version of National Adult Reading Test Nelson 1991 are conducted at baseline 4 months and 10 months after inclusion irrespective of whether patients were following the full training programme intention-to-treat principle
Positive and negative symptom evaluated with Positive and Negative Symptom Scale PANSS
Assessment of health and occupational and general function
Neuropsychological testing of functional level in 7 cognitive domains According to the NIMH-initiative the MATRICS Cognitive Consensus Battery MCCB Nuechterlein et al 2004 includes seven separate cognitive areas See table 1
Current level of competencies in 2 domains of daily life assessed using UCSD Performance-Based Skills Assessment UPSA-B Patterson et al 2001 Danish version
Rosenbergs Self-Esteem Scale Rosenberg 1989 1965 Danish version
Type and dose of antipsychotic medication chlorpromazine equivalents
Table 1 Cognitive test battery
Domain of cognition Tests
1 Speed of information processing BACS Symbol CodingCategory FluencyTrailmaking A
2 Attention CPT-IP Identical Pairs
3 Working memory Spatial SpanLetter-Number SpanTrailmaking B
4 Verbal learning and memory Hopkins Verbal Learning Test-Revised
5 Visuel learning and memory Brief Visuospatial Memory Test-Revised
6 Problem-solving NAB MazesWisconsin Card Sorting Test computerized version64 cards
7 Social cognition MSCEIT Managing Emotions
Ethical considerations and informed consent The project has been approved by the Scientific Ethical Committees for Copenhagen and Frederiksberg and assigned case number KF 01 300017 The guidelines of The Danish Data Inspection and clinicaltrialsgov are followed The interventions and methods of investigation involve no known physical or mental risks Participation is voluntary and written informed consent is obtained All patients are informed both verbally and in written form that they can withdraw from the trial at any time without it having any consequences for their continued treatment
The presence of cognitive deficits in schizophrenia It is a well-established fact that cognitive deficits play a major role in functional outcome in schizophrenia Keefe et al 2006 Gold 2004 Up to 85 patients demonstrate cognitive dysfunctions in the range of 1½-2 SD below norm Fagerlund 2004 Corrigan Penn 2001 Heinrichs Zankanis 1998 Cognitive dysfunctions associated with schizophrenia involve attention information processing memory and executive functions leading to difficulties in learning and poor problem solving abilities
Evidence for the effect of rehabilitation on everyday competencies In spite of the severely debilitating cognitive dysfunctions a relatively large number of patients have shown themselves capable of acquiring new abilities eg Kern et al 2005 Sartory et al 2005 Ueland Rund 2004 Krabbendam Aleman 2003 Pilling et al 2002 Harvey Sharma 2001 Tsang Pearson 2001 Danion et al 2001 Bell et al 2003 Wykes et al 1999 2003 Research has shown that training in symptom handling social proficiency training and supportive provisions in occupational relations apparently can help patients with schizophrenia to function in their daily lives learn solving concrete practical and social tasks and manage relatively independently These improvements enhance self-esteem
Effect studies of cognitive rehabilitation A Cochrane review done by Hayes McGrath 2000 include three small randomized controlled trials and fails to provide conclusive data on evidence for or against cognitive training as a treatment for schizophrenia
Krabbendam Alemans review 2003 of 12 controlled studies finds a weighted mean effect size Cohens d of 045 with 95 CI 026-064 which indicates a small to moderate effect of cognitive training CT for patients with schizophrenia
In Twamley et als review 2003 of 17 randomised controlled studies of CT a weighted mean effect size was calculated across studies The weighted mean effect sizes Cohens d were 032 in improvement in cognitive performance 026 in reduction of symptom severity and 051 in the domain of everyday functioning The review authors recommend longitudinal designs as well as the inclusion of real-life outcome measures in future trials
Many studies of CT have been underpowered small sample sizes which limits the conclusions that can be drawn from results of improvement Ueland Rund 2005 The variability of outcome measures used also complicates interpretation of findings thus a consensus battery MATRICS of outcome measures has been suggested for future studies Silverstein Wilkniss 2004 and Bellack 2004 note that the results of cognitive rehabilitation generally fail to secure the ecological validity wherefore CT ought to be integrated in a broader psychosocial programme of intervention for schizophrenia Other shortcomings in earlier studies include short-term programmes lacking sufficient long-sighted follow-up examinations as well as experimental designs lacking consideration of individual abilities and involvement A recent review of cognitive rehabilitation Velligan et al 2006 underscores the importance of addressing motivation as a primary target
Hogarty et als 2004 promising results from a randomised controlled trial N121 of computer-assisted CT also highlight the importance of examining to what extent the control condition psychosocial treatment improve cognitive functioning Broadly viewed there is sufficient evidence that the combination of CT and psychosocial treatment rather than individually appearing initiatives have the greatest potential for promoting treatment outcome Bell et al 2003
There is a need for a well-organised and sufficiently large randomised clinical trial of the effect of integrated CT and psychosocial rehabilitation In order to examine to what extent CT improves the psychosocial rehabilitation and facilitates new learning one must identify and compare improvements on the level of neuropsychological performance as well as the level of everyday competencies Reeder et al 2006 Buchanan et al 2005 McKibbin et al 2004 The present trial employs a prospective design of 16 weeks with a following follow-up 10 months after inclusion and seeks in the CT to secure an individual adaptation and motivation trough continuous evaluations and level adjustments between patient and trainer
Objectives
1 Primary hypothesis The effect of a 16-weeks programme of computer-based CT integrated in OPUS treatment on the patients competencies in daily life is superior to standard OPUS treatment Primary response variable Total score on UPSA-B Patterson et al 2001 Danish version
2 Secondary hypothesis The effect of a 16-weeks programme CT integrated in OPUS treatment on patients cognitive functioning is superior to standard OPUS treatment Response variables Scores on MATRICS Consensus Cognitive Battery MCCB Trailmaking B and WCST-64 computerized version
3 Tertiary hypothesis The effect of a 16-weeks programme of computer-based CT integrated in OPUS treatment is superior to standard OPUS treatment in terms of patients association with the labour market general health and self-esteem Response variables Occupational status and general functioning measures and Rosenbergs Self-Esteem Scale Rosenberg 1989
Furthermore we want to examine the association between first episode patients cognitive function level and competencies in daily life can be divided in primary and secondary objectives
Blinding The instructor for CT will make a call with participants data to CTU and thereafter inform the patients which intervention programme he or she has been allocated to The study is not blinded in regard to patients cognitive trainers and therapists The blinding applies raters engaged with the outcome evaluation In the follow-up the patient is instructed in advance not to reveal what type of treatment they have received By registering which type of intervention the independent assessors of outcome believe the patient to be receiving it will be evaluated if blinding succeeded The randomised intervention allocation is concealed until the statistical analyses of resulting data have been completed
Participants Patients are recruited from OPUS which is implemented as a standard treatment programme for young adults with firstepisode psychosis in Copenhagen and Århus The staff in OPUS recruit patients to the project The independent assessors interview referred patients and evaluate the following in- and exclusion criteria
Inclusion criteria 1 between 18 and 35 years of age 2 first episode psychosis within F2 spectrum or schizotypal disorder in ICD 10 - post-acute phase of illness 3 sufficient comprehension of Danish 4 written informed consent
Exclusion criteria
1 rejection of participation 2 organic disorder 3 noticeable misuse of psychoactive drugs
Control intervention group All patients receive the treatment usually provided in OPUS
Standard treatment in OPUS consists of affiliation with a primary contact person involvement of family possibility of psychoeducation and social skills training described in details at httpwwwpsykiatriaaadkcent_enhopushtm and wwwopus-kbhdk Depending on individual needs patients are offered to take part in group therapy either social skills training SST or cognitive-behavioral therapy CBT Participation in SST or CBT might be beneficial for both cognition and everyday skills To ensure comparability between the patients allocated to experimental intervention CT and the patients allocated to standard OPUS treatment we stratify patients according to group therapy SSTCBT yesno
Patients randomized to the control group will receive treatment as usual as described above
Experimental intervention A pilot study in OPUS Århus has led to the completion of a manual for a 16-week CT programme for patients with schizophrenia Christensen Olsen 2006
One hour twice a week in 16 weeks patients engage in computer-assisted CT plus one competence dialog every other week Training consists of four modules the first three modules cover the areas of attention memory and executive functions and the last module focus on the cognitive area and related tasks that the individual patient need or prefer to work more on Thus the content of module 4 is based on both the patients and the trainers judgement
Training contains exercises of simple attention attention span and vigilance planning problem solving stimulus-bind and perseveration tendency interaction-based training of working memory and verbal and visual long-term memory The CT approach is oriented towards teaching of compensatory strategies but simple repetition of non-social cognitive tasks on a gradually increasing level of difficulty is also part of the CT program By 90 correct task-completion the level is increased
Module 1 and 2 are based on computertasks COGNIsoft whereas the following modules 3 and 4 include practical everyday tasks In their review Twamley Jeste and Bellack 2003 stress the importance of directly targeting everyday functioning of the patient Thus calendartraining is a vital part of this intervention a way of addressing common difficulties of memory and planning ability Calendartraining and competence dialogues both support environmental adaptation and transference of learning
Training relies on errorless learning principles scaffolding repetition and strategy-learning as recommended by Wykes van der Gaag 1999 Positive reinforcement modelling and verbal instructions are widely used Trainers describe the structure and explain the purpose of training exercises at the beginning of every session to provide a consistent learning environment
Assessments All assessments except Present State Examination-interview PSE clinical version and premorbid IQ DART Danish version of National Adult Reading Test Nelson 1991 are conducted at baseline 4 months and 10 months after inclusion irrespective of whether patients were following the full training programme intention-to-treat principle
Positive and negative symptom evaluated with Positive and Negative Symptom Scale PANSS
Assessment of health and occupational and general function
Neuropsychological testing of functional level in 7 cognitive domains According to the NIMH-initiative the MATRICS Cognitive Consensus Battery MCCB Nuechterlein et al 2004 includes seven separate cognitive areas See table 1
Current level of competencies in 2 domains of daily life assessed using UCSD Performance-Based Skills Assessment UPSA-B Patterson et al 2001 Danish version
Rosenbergs Self-Esteem Scale Rosenberg 1989 1965 Danish version
Type and dose of antipsychotic medication chlorpromazine equivalents
Table 1 Cognitive test battery
Domain of cognition Tests
1 Speed of information processing BACS Symbol CodingCategory FluencyTrailmaking A
2 Attention CPT-IP Identical Pairs
3 Working memory Spatial SpanLetter-Number SpanTrailmaking B
4 Verbal learning and memory Hopkins Verbal Learning Test-Revised
5 Visuel learning and memory Brief Visuospatial Memory Test-Revised
6 Problem-solving NAB MazesWisconsin Card Sorting Test computerized version64 cards
7 Social cognition MSCEIT Managing Emotions
Ethical considerations and informed consent The project has been approved by the Scientific Ethical Committees for Copenhagen and Frederiksberg and assigned case number KF 01 300017 The guidelines of The Danish Data Inspection and clinicaltrialsgov are followed The interventions and methods of investigation involve no known physical or mental risks Participation is voluntary and written informed consent is obtained All patients are informed both verbally and in written form that they can withdraw from the trial at any time without it having any consequences for their continued treatment
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| Lundbeckfonden | None | None | None |
| Danish Research Counsil | None | None | None |
| Bristol-Myers Squibbs | None | None | None |
| Sygekassernes Helsefond | None | None | None |