Clinical trial NCT01764568: Contrasting Group Therapy Methods for Psychosis
Official title: Functional Brain Networks Underlying Non-pharmaceutical Interventions for Psychosis.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Psychosis
Schizophrenia
Schizoaffective Disorder
Schizophreniform Disorder
Keywords: Metacognitive training
Cognitive behavioral therapy
Clinical trial
Group intervention
Group therapy
Schizophrenia
Psychosis
Cognitive remediation
Lead sponsor: University of British Columbia
Sponsor class: OTHER
Collaborators: name: Vancouver Coastal Health Research Institute
name: Vancouver General Hospital
name: Vancouver Coastal Health
name: VGH and UBC Hospital Foundation
First posted: 2013-01-09
Enrollment: 129
Sex: ALL
Minimum age (years): 19
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: Current Canadian Clinical Practice guidelines emphasize the need for effective psychosocial adjuncts to pharmacotherapy for schizophrenia (Canadian Psychiatric Association 2005). This randomized control trial seeks to contribute to the body of evidence supporting psychosocial treatments by assessing the effectiveness of metacognitive training (MCT) and cognitive remediation (CR) at treating the persistent positive and cognitive symptoms of schizophrenia. MCT is a therapy designed to improve patient awareness and insight into the cognitive biases that are frequently seen in schizophrenia; it has been associated with decreased psychopathology (specifically decreased positive symptoms) and improved psychosocial function. CR is a therapy designed to improve performance in a variety of neurocognitive functions such as attention, memory, and executive functioning; it has been associated with improved cognitive and psychosocial functioning. Both MCT and CR will be compared to treatment as usual (TAU) as done previously (Kumar er al., 2010; Moritz et al., 2011).

Hypotheses:

1. MCT will produce greater change in delusions (severity and conviction) than CR and TAU.
2. CR and MCT will produce greater change in social/everyday functioning than TAU.
3. CR will produce greater improvement in basic attention and memory measures relative to MCT and TAU.
4. MCT will produce greater reduction on tasks measuring targeted reasoning biases relative to CR and TAU.
5. CR will increase efficiency of functional networks on a working memory task relative to MCT and TAU.
6. MCT will lead to a greater decrease in the neural response to evidence matches relative to CR and TAU.

Detailed description: Objectives:

The objectives of this research project is to assess the relative effectiveness of MCT and CR at treating the persistent positive symptoms of schizophrenia in a stable patient population. Specifically, we will use verified measures to examine the impact of these interventions on delusion conviction and severity, as well as on other features of interest, including insight and specific cognitive biases. We will use functional neuroimaging, both electroencephalography (EEG) and functional Magnetic Resonance Imaging (fMRI), to measure the changes in the neural responses while subjects are performing various cognitive tasks. It is expected that improvements in cognitive performance and function seen with MCT and CR correlate with select improvements in efficiency of particular brain networks. We anticipate a double dissociation, in that subjects with decreased positive symptoms following MCT may present with different patterns of activation than those with improved neurocognitive function following CR.

Procedures:

Recruitment will be done through inpatient and outpatient departments in Vancouver, British Columbia, Canada. Diagnosis of schizophrenia spectrum disorder will be confirmed using the MINI (Sheehan, 1998). Both inpatients and outpatients will be recruited; patients must be identified as suitable, as determined by their treating psychiatric team. This will suffice to obtain 50 subjects per condition over 5 years. Note that our intended sample size was originally 75 per group, which would allow for attrition and still give us an estimated 50 subjects with completed and valid behavioural and neuroimaging data.

Participants who complete the screening and baseline (pre-treatment) assessments will be randomly assigned to one of 3 conditions: 1) MCT, 2) CR, or 3) TAU. Randomization of subjects will occur as they complete their baseline assessments, and entry into the groups will involve a rolling intake model. Interventions will be administered twice weekly for 8 weeks. The groups will be run by Clinical Psychologists and PhD level psychology students. Allied health professionals, such as Occupational Therapists or Social Workers, may co-facilitate groups.

Baseline (pre-treatment), midpoint, and post-treatment assessments will include symptom and cognitive assessment, as well as self-reported measures, as outlined above. Patients who are willing and eligible will also be involved in three tasks in which we will record both fMRI data and EEG data.

fMRI scanning:

Participants will be prepared for EEG by trained graduate students, research staff, and fMRI technicians. Once in the scanner, the subject will perform three cognitive tasks which have been used extensively in previous research.

EEG recording:

Participants will be prepared for EEG by trained graduate students and research staff. The subjects will perform the same cognitive tasks as the fMRI procedure.

Measurements:

Symptom Ratings:

General psychopathology will be assessed using the Scale for the Assessment of Negative Symptoms (SANS; Andreasen, 1984) and the Scale for the Assessment of Positive Symptoms (SAPS; Andreasen, 1984). Delusion severity will be measured using the Delusions Scale of the Psychotic Symptom Rating Scales (PSYRATS; Haddock, McCarron, Tarrier, \& Faragher, 1999). All symptom rating scales will be administered by trained raters blinded to the treatment allocations of subjects.

Self-Report Measures:

Patient depressive symptoms will be measured using the Beck Depression Inventory, Second Edition (BDI-II, Beck, 1996). Patient perception of their quality of life will be measured using the World Health Organisation Quality of Life scale (WHOQoL). Patient perception of stigma and its impact on their quality of life will be measured using the Internalized Stigma of Mental Illness scale (ISMI; Ritsher et al., 2003). Patient perceptions of self and self-esteem will be measured using the Rosenberg Self-Esteem Scale (RSES; Rosenberg, 1965).

Cognitive Biases

MCT for psychosis is fundamentally concerned with dysfunctional thinking in psychotic illnesses and it directly targets cognitive biases known to be involved in delusional thinking including the jumping to conclusions bias, the attributional bias, and the bias against disconfirmatory evidence. Two cognitive biases commonly seen in schizophrenia will be evaluated using the "jumping to conclusions (JTC) task" (also known as the "fisherman" task) and the "bias against disconfirmatory evidence (BADE)" task. These tasks were developed, in part, by the Principal Investigator and have been described in previous research (Lecomte \& Woodward, 2005; Woodward 2006a; Woodward 2006b; Woodward 2007; Moritz \& Woodward 2005; Woodward 2009).

The test of Premorbid Function (ToPF) is a word-reading task that will be used to estimate the premorbid intelligence (IQ) of the individual (Wechsler, 2011). The Wechsler Abbreviated Scale of Intelligence, Second Edition (WASI-II; Wechsler, 2011) will provide a measure of current intelligence (IQ). The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS; Randolph, 1998) will be used to review neurocognitive function of the individual, including attention, processing speed, working memory, verbal and visual memory. The trailmaking test will provide measures of basic attention, speed of processing, mental flexibility, and executive functioning (Reitan, 1992). The Controlled Oral Word Association test (COWAT; Benton et al., 1994) is a verbal fluency task that measures executive functioning.

Insight

The Beck Cognitive Insight Scale (BCIS; Beck, Baruch, Balter, Steer, \& Warman, 2004) will be administered to evaluate patients' degree of insight into cognitive biases and limitations.

Functional Neuroimaging and Electroencephalography

Functional Magnetic Resonance Imaging (fMRI) and Electroencephalography (EEG) will be used to assess the relative involvement and activation of different neural networks. The Sternberg Working Memory Task will be used in order to quantify the level of efficiency of the neural networks responsible for working memory (Metzak et al., 2012). Two Evidence Matching Tasks (e.g., the "fish task" and the "bias against discomfirmatory evidence (BADE) task") will be used in order to quantify the reactivity of the neural networks responsible for evidence matching (e.g., anterior-cingulate-based network; Woodward et al., 2008).

Feedback from Participants

After the final session in active treatment conditions, patients will be asked to complete a questionnaire comprising 10 questions on acceptance and subjective efficacy (Moritz \& Woodward 2007a). Data accumulated therein will be used together with frequency of unattended sessions to establish acceptability and feasibility of the various treatment conditions.

Statistical Analysis

Rolling group intake and facilitation will allow for two to four, two-month cycles of each condition per year for 5 years, which should allow us to obtain 75 subjects per condition. This would allow for possible attrition, and still give us an estimated 50 subjects per condition (MCT, CR, TAU), which is sufficient to produce a power of 0.8 to detect a large effect in a three group means comparison design (Cohen 1992) using p=0.05 as the cutoff for significance.

Notes on Actual Enrollment (As the Study Has Been Terminated)

Out of the intended enrollment of 225 subjects (75 subjects per group), 129 subjects were actually enrolled. Of these 129 subjects actually enrolled, approximately 60 subjects have a completed dataset.

Eligibility criteria: Inclusion Criteria:

1. Between the ages of 19 to 60 years
2. Diagnosis of schizophrenia, schizoaffective disorder or schizophreniform disorder.
3. Diagnosis of mood disorder with current psychosis.

Exclusion Criteria:

1. An inability to read and write in English. Participants must be have used English on a daily basis for at least 5 years, and must be able to understand the consent form and give written consent.
2. A history of severe neurological disorder and those with severe manifestations of hostility, megalomania, formal thought disorder and suspiciousness.
3. Subjects who are obtaining ongoing electroconvulsive therapy (ECT)
4. Subjects who are consistently disrupting the rest of the group might be asked to leave, this will be at the discretion of the group instructor.

In addition to the group exclusion criteria, the exclusion criteria for Neuroimaging (fMRI):

1. History of brain damage or other medical problems that may affect comprehension (e.g., seizure disorders, stroke, aneurysm, brain tumor, etc.)
2. Psychosis that is a direct consequence of substance abuse.
3. Currently suffer from severe substance dependence.
4. Surgery within the last 6 weeks.
5. Surgery to the brain, heart or eyes.
6. Metal implants
7. Metal fragments in or near your eyes.
8. Pregnant.
9. Recent serious concussion, or loss of consciousness of more than 10 minutes.
10. Colour blind

In addition to the group exclusion criteria, the exclusion criteria for Neuroimaging EEG:

1. History of brain damage or other medical problems that may affect comprehension (e.g., seizure disorders, stroke, aneurysm, brain tumor, etc.)
2. Recent serious concussion, or loss of consciousness of more than 10 minutes
3. Currently suffer from severe substance dependence.
4. Colour blind

Primary outcomes:
measure: Delusion Severity
timeFrame: 8-12 weeks (post-treatment) relative to baseline (pre-treatment)
Secondary outcomes:
measure: Symptom Ratings
timeFrame: 4 weeks (midpoint of therapy) relative to baseline (pre-treatment)
measure: Symptom Ratings
timeFrame: 8-12 weeks (post-treatment) relative to baseline (pre-treatment)
measure: Cognitive Function
timeFrame: Pre-treatment (prior to commencement of therapy)
measure: Cognitive Function
timeFrame: 4 weeks (midpoint of therapy) relative to baseline (pre-treatment)
measure: Cognitive Function
timeFrame: 8-12 weeks (post-treatment) relative to baseline (pre-treatment)
measure: Cognitive Bias
timeFrame: 4 weeks (midpoint of therapy) relative to baseline (pre-treatment)
measure: Cognitive Bias
timeFrame: 8-12 weeks (post-treatment) relative to baseline (pre-treatment)
measure: Insight
timeFrame: 4 weeks (midpoint of therapy) relative to baseline (pre-treatment)
measure: Insight
timeFrame: 8-12 weeks (post-treatment) relative to baseline (pre-treatment)
measure: Psychosocial/Everyday Functioning
timeFrame: 4 weeks (midpoint of therapy) relative to baseline (pre-treatment)
measure: Psychosocial/Everyday Functioning
timeFrame: 8-12 weeks (post-treatment) relative to baseline (pre-treatment)
measure: Feasibility and acceptability
timeFrame: 8-12 weeks (post-treatment)
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: UBC Hospital - Detwiller Pavilion
state: British Columbia
Study officials:
affiliation: University of British Columbia
name: Todd Woodward, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of British Columbia
name: Mahesh Menon, PhD, RPsych
role: PRINCIPAL_INVESTIGATOR
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