Promoting Activity and Cognitive Enrichment in Schizophrenia (PACES)

Study Overview
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Brief Summary
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This project will conduct a confirmatory efficacy trial of two novel psychosocial interventions, Cognitive Enhancement Therapy and Enriched Supportive Therapy, for the treatment of persistent negative symptoms in schizophrenia.

Detailed Description
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This project will conduct a confirmatory efficacy trial to examine the efficacy of Cognitive Enhancement Therapy (CET) and Enriched Supportive Therapy (EST) for the treatment of schizophrenia patients with significant and persistent negative symptoms. A total of 90 stabilized schizophrenia outpatients with moderate-to-severe persistent negative symptoms will be randomized to 18 months of CET or EST. Comprehensive data on persistent negative symptoms, social and non-social cognition, and functional outcome will be collected prior to treatment and at frequent 6-month intervals to (1) confirm the efficacy of CET and EST for improving persistent negative symptoms; (2) confirm the impact of cognitive target engagement on reduced negative symptoms; and (3) examine the short-term durability of CET and EST effects on negative symptoms and functioning.

Official Title
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Cognitive Enhancement for Persistent Negative Symptoms in Schizophrenia

Conditions
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Schizophrenia

Intervention / Treatment
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* Behavioral: Cognitive Enhancement Therapy
* Behavioral: Enriched Supportive Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inclusion criteria will be evaluated longitudinally in a 4-week evaluation period. Patients will be included if they are outpatients and: are between 18-60 years of age; have a diagnosis of schizophrenia or schizoaffective disorder confirmed by the SCID; have a clinical history of persistent negative symptoms lasting at least 3 months as identified from the medical record; have observed persistent negative symptoms at the beginning and end of the 4-week evaluation period; have been stabilized on antipsychotic medication at the beginning and end of the 4-week evaluation period; have stabilized depressive symptoms at the beginning and end of the 4-week evaluation period; have mild or absent extrapyramidal symptoms at the beginning and end of the 4-week evaluation period; have had changes to their primary antipsychotic medication within the previous 3 months; have current IQ > 80; and are able to read (sixth grade level or higher) and speak fluent English. - Exclusion Criteria: Exclusion criteria are intended to avoid likely treatment confounders and contraindications and include: the presence of organic brain syndrome; comorbid medical disorders producing cognitive impairment (e.g., mild brain injury, previous concussions with loss of consciousness); persistent suicidal or homicidal behavior; significant clinician-estimated medication non-adherence; and SCID-verified substance use disorder.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: This proposed study consists of an 18-month randomized-controlled trial in which 90 outpatients with schizophrenia with moderate-to-severe persistent negative symptoms will be randomized to Cognitive Enhancement Therapy (CET) or Enriched Supportive Therapy (EST) and treated for 18 months. Comprehensive measures of cognition, negative symptoms, and functional outcome will be collected prior to treatment, every 6-months thereafter (6 and 12 months), at treatment completion (18 months), and 3-month (21 months) and one year (30 months) post-treatment follow-up to provide a rigorous confirmatory test of the efficacy of CET and EST for patients with persistent negative symptoms and the cognitive mechanisms of negative symptom improvement in the disorder.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cognitive Enhancement Therapy<br>This research treatment aims to help with problems in thinking, planning, and socialization. Participants begin with cognitive training using computer software programs. They also participate in a small social-cognitive group to learn about their condition and how to act wisely in social situations by developing the abilities needed to understand another person's perspective, evaluate social contexts, and be foresightful. Time commitment: about 3½ hours per week; Location: Pittsburgh, PA only | Behavioral: Cognitive Enhancement Therapy<br>* An 18-month comprehensive, small group approach for the remediation of cognitive deficits in neurodevelopmental disorders consisting of individual sessions and 45 group training sessions in social cognition that are integrated with approximately 60 hours of computer assisted training in attention, memory, and problem solving skills.<br>* Other names: CET;|
| Active Comparator: Enriched Supportive Therapy<br>This research treatment uses individual supportive therapy to help patients learn about schizophrenia, manage their emotions and stress, improve their social skills, and cope with everyday problems. Participants will learn about the impact of stress on their lives, and how to identify their own early cues of distress and apply effective coping strategies. Time commitment: about 2 hours per week; Location: Pittsburgh, PA only | Behavioral: Enriched Supportive Therapy<br>* An 18-month intervention that uses individual supportive therapy to help patients learn about schizophrenia, manage their emotions and stress, improve their social skills, and cope with everyday problems. Participants will learn about the impact of stress on their lives, and how to identify their own early cues of distress and apply effective coping strategies.<br>* Other names: EST;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Persistent Negative Symptoms | Negative symptoms will be assessed using the Clinical Assessment Interview for Negative Symptoms (CAINS). The CAINS is a structured interview measure of expressive and motivational negative symptoms consisting of 13 items based on a standardized interview with anchor points for each rating. This measure was developed to address the limitations of previous negative symptom measures and designed for use in clinical trials of negative symptom therapeutics. This outcome has two endpoints that will be evaluated in this trial, persistent negative symptoms related to expression (Expression subscale) and persistent negative symptoms related to motivation/pleasure (Motivation/Pleasure subscale). Items are rated on a 0 to 4 scale, with higher scores indicating greater negative symptom severity. | Prior to treatment, 6 months, 12, months, 18 months, 21 months and 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Functioning | A composite index of functional outcomes will be derived from measures of social adjustment commonly used in schizophrenia research. These are clinical interview-based measures of functioning, with some self-report measures, covering vocational, social, family, and other functional outcome domains. Measures will include the Social Adjustment Scale-II, Major Role Adjustment Inventory, the Global Assessment of Functioning, and other field standards of functional outcome in schizophrenia. Because these measures do not share a common Unit of Measure and because of the large number of functional outcome measures used, a composite index will be formed to assess changes in functioning to reduce Type I error from multiple inference testing. | Prior to treatment, 6 months, 12, months, 18 months, 21 months and 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Negative Symptoms, Cognition, Social Cognition