Promoting Activity and Cognitive Enrichment in Schizophrenia (PACES)

• ClinicalTrials.gov Identifier: NCT04143126
• Recruitment Status: Recruiting
• First Posted: October 29, 2019
• Last Update Posted: October 6, 2020
• Sponsor: University of Pittsburgh
• Collaborator: National Institute of Mental Health (NIMH)
• Information provided by (Responsible Party): Shaun M. Eack, University of Pittsburgh

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Schizophrenia	Behavioral: Cognitive Enhancement Therapy; Behavioral: Enriched Supportive Therapy	Not Applicable

Detailed Description:

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 90 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention 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 post-treatment follow-up (21 months) 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 (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Cognitive Enhancement for Persistent Negative Symptoms in Schizophrenia
• Actual Study Start Date: October 1, 2019
• Estimated Primary Completion Date: March 30, 2024
• Estimated Study Completion Date: June 30, 2024

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cognitive Enhancement Therapy; 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; 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.; Other Name: CET
Active Comparator: Enriched Supportive Therapy; 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; 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.; Other Name: EST

Outcome Measures

Primary Outcome Measures :

1. Change in Persistent Negative Symptoms [ Time Frame: Prior to treatment, 6 months, 12, months, 18 months, and 21 months ]
   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.

Secondary Outcome Measures :

1. Change in Functioning [ Time Frame: Prior to treatment, 6 months, 12, months, 18 months, and 21 months ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 50 Years (Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

Inclusion criteria will be evaluated longitudinally in a 4-week evaluation period. Patients will be included if they are outpatients and:

1. are between 18-50 years of age;
2. have a diagnosis of schizophrenia or schizoaffective disorder confirmed by the SCID;
3. have a clinical history of persistent negative symptoms lasting at least 3 months as identified from the medical record;
4. have observed persistent negative symptoms at the beginning and end of the 4-week evaluation period;
5. have been stabilized on antipsychotic medication at the beginning and end of the 4-week evaluation period;
6. have stabilized depressive symptoms at the beginning and end of the 4-week evaluation period;
7. have mild or absent extrapyramidal symptoms at the beginning and end of the 4-week evaluation period;
8. have had changes to their primary antipsychotic medication within the previous 3 months;
9. have current IQ > 80; and
10. 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:

1. the presence of organic brain syndrome;
2. comorbid medical disorders producing cognitive impairment (e.g., mild brain injury, previous concussions with loss of consciousness);
3. persistent suicidal or homicidal behavior;
4. significant clinician-estimated medication non-adherence; and
5. SCID-verified substance use disorder.

Contacts and Locations

Contacts

Contact: Shaun M Eack, PhD; 412-246-5958; sme12@pitt.edu

Contact: Michelle M Perrin, MBA; 412-683-7524; perrinm@upmc.edu

Locations

United States, Pennsylvania

University of Pittsburgh; Recruiting

Pittsburgh, Pennsylvania, United States, 15213

Contact: Shaun Eack, PhD sme12@pitt.edu

Principal Investigator: Shaun Eack, PhD

Sponsors and Collaborators

University of Pittsburgh

National Institute of Mental Health (NIMH)

More Information

• Responsible Party: Shaun M. Eack, Professor, University of Pittsburgh
• ClinicalTrials.gov Identifier: NCT04143126
• Other Study ID Numbers: STUDY19050382; R01MH118267 ( U.S. NIH Grant/Contract )
• First Posted: October 29, 2019
• Last Update Posted: October 6, 2020
• Last Verified: September 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: The proposed study has a data sharing plan consistent with NIH policy. Data will be de-identified before sharing on a need to know basis. Sharing will be executed with an approved data transfer agreement.
• Time Frame: Final data that has not yet been published will be shared after acceptance of publication of the relevant paper.
• Access Criteria: Data sharing will occur at two levels:1) specific requests to analyze data from investigators in the field and 2) collaboration with NIH to facilitate data sharing activities for the NIMH National Database for Clinical Trials Related to Mental Illness (NDCT).

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Shaun M. Eack, University of Pittsburgh:

Negative Symptoms; Cognition; Social Cognition

Additional relevant MeSH terms:

Schizophrenia; Schizophrenia Spectrum and Other Psychotic Disorders; Mental Disorders