Psychosocial Therapy and Risperidone Treatment in Work Performance in Recent-Onset Schizophrenia

Study Overview
=================
Brief Summary
-----------------
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.

Detailed Description
-----------------
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 once 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.

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

Conditions
-----------------
Schizophrenia

Intervention / Treatment
-----------------
* Behavioral: Cognitive remediation training (CT)
* Behavioral: Healthy behavior training (HBT)
* Drug: Risperidone, administered orally (Oral Ris)
* Drug: Risperidone, administered via injection (RLAI)


Participation Criteria
=================
Eligibility Criteria
-----------------
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 intelligence quotient (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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cog Remediation, risperidone injection<br>Participants will receive cognitive remediation training plus risperidone, administered via injection. | Behavioral: Cognitive remediation training (CT)<br>* Cognitive remediation training includes computerized cognitive training plus learning skills group.<br>Drug: Risperidone, administered via injection (RLAI)<br>* Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed<br>* Other names: Risperdal Consta;|
| Active Comparator: Healthy Behavior Training, risperidone injection<br>Participants will receive health behavior training plus risperidone, administered via injection. | Behavioral: Healthy behavior training (HBT)<br>* Healthy behavior training includes group skills training in nutrition, exercise, and relaxation.<br>Drug: Risperidone, administered via injection (RLAI)<br>* Risperidone in injectable form every 2 weeks, starting with 25 mg and adjusted as needed<br>* Other names: Risperdal Consta;|
| Experimental: Cog Remediation, oral risperidone<br>Participants will receive cognitive remediation training plus risperidone administered orally. | Behavioral: Cognitive remediation training (CT)<br>* Cognitive remediation training includes computerized cognitive training plus learning skills group.<br>Drug: Risperidone, administered orally (Oral Ris)<br>* Oral risperidone at dosage judged optimal by treating psychiatrist<br>* Other names: Risperdal;|
| Active Comparator: Healthy Behavior Training, oral risperidone<br>Participants will receive health behavior training plus risperidone administered orally. | Behavioral: Healthy behavior training (HBT)<br>* Healthy behavior training includes group skills training in nutrition, exercise, and relaxation.<br>Drug: Risperidone, administered orally (Oral Ris)<br>* Oral risperidone at dosage judged optimal by treating psychiatrist<br>* Other names: Risperdal;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) | Values presented here are the changes in MCCB Overall Composite T scores from baseline to 12 months, with higher values representing better outcome. Raw test scores are used to generate T-scores and then the seven MCCB domains are combined to generate an Overall Composite T score. MCCB Overall Composite T scores have a mean in the general population of 50 with a standard deviation of 10. Thus, a positive change of 5 T scores is an improvement of half a standard deviation. | Measured at baseline and 12 months | 
| Work/School Functioning (Global Functioning Scale: Role) | Change in role functioning from baseline to the 6 month point (rated on a scale from 1= Extreme Role Dysfunction to 10 = Superior Role Functioning) is presented here. | Baseline to 6 months | 
| Average Medication Non-adherence | 5-point scale (1 = best adherence, 5= nonadherent) based on pill counts, Medication Event Monitoring System (MEMS) cap readings, plasma assays, and psychiatrist judgements for oral risperidone and timing of injections for long-acting injectable risperidone. Averaged over medication study participation. | Averaged over study participation (up to 12 months) | 
| Work/School Functioning (Global Functioning Scale: Role) | Changes in role functioning from baseline to 12 months. Ratings on a 10-point scale with 10 being best. | Baseline to 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Work Behavior Inventory (WBI) Quality of Work/School Performance | Change in rating on quality of work/school performance based on patient, employer, and/or teacher reports. The Quality of Work rating at baseline was subtracted from the same rating at 12 mos. Higher scores are better outcome. | Baseline to 1 year | 
| Maintenance of Work/School Attendance | Modified Work Section of the Social Adjustment Scale (SAS) was used to calculate the total number of weeks in school or competitive work. Range of possible values is 0 to 52, with higher numbers being better outcome. | 12 months | 
| Exacerbation or Relapse of Psychotic Symptoms | Dichotomous measure: Presence of any of 3 psychotic relapse or exacerbation categories scored from the Brief Psychiatric Rating Scale (BPRS) occurring after randomization and until end of study participation (up to 12 months post baseline). BPRS was administered every two weeks throughout study participation. | Occurence after randomization and until end of study participation (up to 12 mos.) | 
| Retention in Treatment | Days after randomization that a participant continued to receive at least the assigned CT or HBT psychosocial treatment. If a participant needed to end the assigned medication condition (RLAI vs. Oral Ris), they continued in the psychosocial treatment so this outcome focused on the days in the assigned psychosocial treatment. Possible range is 1 to 365, with higher being a better outcome. | 12 months | 
| Awareness of Illness, as Assessed by the Scale to Assess Unawareness of Mental Disorder, Revised Version (SUMD-R) | Rating scale based on clinician's interview of patient to determine level of lack of awareness of having a mental disorder. Range is from 1 (Aware) to 5 (Unaware), so lower scores indicate better outcome. | 12 months after randomization | 
| Change in Motivation for Work/School | The Work Motivation scale is a factor score from the Work Personality Profile. The Work Personality Profile is a set of ratings based on interviewing the participant. Scores at each occasion can range from 8 to 32, with higher indicating better motivation. Scores reported here are changes from baseline to 12 months, which could range from -24 to 24 with higher being better. | Baseline to 12 months | 
| Change in Coping Strategies | Coping Response Inventory, which rates extent to which active coping strategies were used after a significant stressful life event. Range of possible scores is 1 to 4. Higher scores are better. | Baseline to 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Schizoaffective Disorder, Depressed Type, Schizophreniform Disorder, First-Episode Schizophrenia, Supported Employment, Cognitive Remediation, Health Behavior Training, Antipsychotic Medication