Official Title: “Developmental Processes in Schizophrenic Disorders: Cognitive Remediation, Medication Adherence, and Work Outcome in Recent-Onset Schizophrenia”

This study will determine the effectiveness of various combinations of psychosocial therapy and risperidone treatment in improving work or school performance in people with first-episode schizophrenia.

Study Type: Interventional

Study Design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study

Study Primary Completion Date: March 2011

Schizophrenia is a chronic, severe, and disabling brain disorder. People with schizophrenia often experience hallucinations, delusions, thought disorders, and movement disorders. These symptoms make it difficult to maintain a job, participate in school, and keep up self-care.

Proper treatment of first-episode schizophrenia may increase the chances of controlling disease progression on a long-term basis. Antipsychotic medications, such as risperidone, and psychosocial treatments, such as cognitive enhancement training and health behavior training, are common, effective treatments for schizophrenia. This study will determine the effectiveness of various combinations of psychosocial therapy and risperidone treatment in improving work or school performance in people with first-episode schizophrenia.

Participants in this open label study will be randomly assigned to receive one of the following four combinations of an antipsychotic medication and a psychosocial treatment:

cognitive enhancement training plus oral risperidone; cognitive enhancement training plus long-acting injectable risperidone; health behavior training plus oral risperidone; or health behavior training plus long-acting injectable risperidone. Cognitive enhancement training will entail 2 hours per week of computer-assisted training targeted at improving attention, memory, and problem-solving skills. Additionally, participants will attend a weekly 1-hour group meeting to learn how to apply these skills to work and school situations. Health behavior training will involve 3 hours per week of relaxation training, nutrition education, and physical exercise to enhance wellness. Participants assigned to receive oral risperidone will receive their medication in pill form at the dosage determined to be optimal by the study psychiatrist. Participants assigned to receive injectable risperidone will be given one injection every 2 weeks. Dosages will start at 25 mg per injection and will be adjusted as needed.

Treatment will continue for 1 year following dosage stabilization, which typically occurs 2 to 3 months following study entry. For the first 6 months, participants assigned to receive health behavior training will attend study visits once a week and participants assigned to receive cognitive enhancement training will attend study visits twice a week. For the final 6 months, all participants will attend study visits twice weekly. At each visit, participants will receive their assigned psychosocial treatment; attend group therapy; meet with a case manager for counseling and assessment of symptoms, work functioning, and social functioning; and meet with a psychiatrist to monitor medication response. Additional cognitive and health behavior measures will be taken every 6 months to assess treatment effectiveness.

Intervention(s) in this Clinical Trial

• Behavioral: Cognitive remediation
  • Cognitive remediation training includes computerized cognitive training plus learning skills group.
• Behavioral: Health behavior training
  • Health behavior training includes group skills training in nutrition, exercise, and relaxation.
• Drug: Risperidone, administered orally
  • Oral risperidone at dosage judged optimal by treating psychiatrist
• Drug: Risperidone, administered via injection
  • Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed
• Behavioral: Individual Placement and Support
  • Supported education/employment

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • Participants will receive cognitive remediation training plus injectable, long-acting risperidone.
• Active Comparator: 2
  • Participants will receive health behavior training plus injectable, long-acting risperidone.
• Experimental: 3
  • Participants will receive cognitive remediation training plus risperidone administered orally.
• Active Comparator: 4
  • Participants will receive health behavior training plus risperidone administered orally.

Primary Measures

• Cognitive performance on test battery (Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery plus additional measures)
  • Time Frame: Measured at Months 6 and 12
    Safety Issue?: No
• Return to work or school (SAS Work Section)
  • Time Frame: Measured every 3 months for 1 year
    Safety Issue?: No
• Maintenance of work/school attendance (SAS)
  • Time Frame: Measured every 3 months for 1 year
    Safety Issue?: No
• Quality of work or school functioning, as assessed by the Work Behavior Inventory (WBI)
  • Time Frame: Measured every 2 months for 1 year
    Safety Issue?: No
• Medication adherence
  • Time Frame: Measured every 2 weeks for 1 year
    Safety Issue?: No

Secondary Measures

• Measured over 12 months: Exacerbation or relapse of psychotic symptoms, as assessed by the Brief Psychiatric Rating Scale (BPRS)
  • Time Frame: Every 2 weeks
    Safety Issue?: No
• Retention in treatment
  • Time Frame: Every 3 months
    Safety Issue?: No
• Awareness of illness, as assessed by the Scale to Assess Unawareness of Mental Disorder, Revised Version (SUMD-R)
  • Time Frame: Every 6 months
    Safety Issue?: No
• Increased motivation for work/school
  • Time Frame: Every 6 months
    Safety Issue?: No
• Improved coping strategies
  • Time Frame: Every 6 months
    Safety Issue?: No

Inclusion Criteria:

• Diagnosis of schizophrenia, schizoaffective disorder (depressed type), or schizophreniform disorder
• First major episode of psychotic symptoms occurred within 2 years prior to study entry

Exclusion Criteria:

• Neurological disorder or injury (e.g., encephalitis, epilepsy, traumatic brain injury)
• Mental retardation (e.g., premorbid IQ less than 70)
• Significant alcohol or substance use during last 6 months
• Unable to complete research measures in English
• Any condition that may make risperidone use medically inadvisable

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 45 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Sponsor: National Institute of Mental Health (NIMH)

Overall Clinical Trial Officials and Contacts

Keith H. Nuechterlein, PhD Principal Investigator University of California, Los Angeles, Department of Psychiatry and Biobehavioral Sciences  

Overall Contact: Rosemary Collier, MA 310-206-5090 rcollier@mednet.ucla.edu

Information obtained from ClinicalTrials.gov on November 19, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00333177

Study ID Number: R01 MH37705-06

ClinicalTrials.gov Identifier: NCT00333177

Health Authority: United States: Federal Government