Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)

Study Overview
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Brief Summary
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This study will evaluate the safety and efficacy of risperidone (Risperdal®), olanzapine (Zyprexa®), and molindone (Moban®) for the treatment of children and adolescents with schizophrenia or schizoaffective disorder.

Detailed Description
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Little research has been conducted on the use of psychotropic agents in children and adolescents with early onset schizophrenia spectrum disorders. This study will compare antipsychotic agents with different mechanisms of action in children and adolescents who have schizophrenia or schizoaffective disorder with active psychotic symptoms. Participants are randomly assigned to receive risperidone (Risperdal), olanzapine (Zyprexa), or molindone (Moban) for 8 weeks. After 11/2005, no additional patients will be assigned to olanzapine treatment. Patients with significant improvement and without side effects continue maintenance therapy for another 44 weeks. Participants who show significant negative symptoms after 8 weeks may be started on a mood stabilizer or antidepressant. Weight gain, metabolic changes, neurocognition, functional outcome, psychotic symptoms, extrapyramidal side effects, and the ability to sustain effective therapy over time are assessed.

Official Title
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Treatment of Schizophrenia and Related Disorders in Children and Adolescents

Conditions
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Schizophrenia

Intervention / Treatment
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* Drug: Risperidone
* Drug: Olanzapine (enrollment closed in this treatment)
* Drug: Molindone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Schizophrenia, schizophreniform disorder, or schizoaffective disorder with psychotic symptoms Free of depot antipsychotic medication for at least 6 months. Oral antipsychotic medication at entry into the study is allowed, provided the participant has not had an adequate trial during the present episode of psychosis. If taking antidepressant or mood stabilizing medication, stable dosing for at least 30 days prior to entry. Good physical health Exclusion Criteria: Risperidone (RIS), olanzapine (OLA)*, or molindone (MOL) for 8 weeks or more during THIS episode, with 2 weeks at the maximal dose (6 mg/day of RIS, 20 mg/day of OLA, or 140 mg/day of MOL) If using antidepressant and/or mood stabilizing medications, treatment for fewer than 30 days immediately before entry Intolerance or nonresponse to RIS, OLA*, or MOL during any previous treatment Bipolar affective disorder,post traumatic stress disorder, personality disorder, or psychosis not otherwise specified Currently meeting Diagnostic and Statistical Manual version IV (DSM IV) criteria for major depression episode DSM IV criteria for substance abuse or dependence with intention to continue illicit substance abuse Endocrinological or neurological conditions which confound the diagnosis or are a contraindication to treatment with antipsychotics Mental retardation Risk of suicide or homicide that is not adequately controlled in the current setting Pregnancy or refusal to practice contraception during the study * OLA exclusion not applicable after 11/2005

Ages Eligible for Study
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Minimum Age: 8 Years
Maximum Age: 19 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: olanzapine<br>oral olanzapine 5-20mg per day for up to 52 weeks | Drug: Olanzapine (enrollment closed in this treatment)<br>* oral olanzapine 5-20mg per day for up to 52 weeks<br>* Other names: Zyprexa;|
| Active Comparator: risperidone<br>oral risperidone 0.5mg to 6mg daily for up to 52 weeks | Drug: Risperidone<br>* oral risperidone 0.5mg to 6mg daily for up to 52 weeks<br>* Other names: Risperdal;|
| Active Comparator: molindone<br>oral molindone from 10-140mg/daily for up to 52 weeks | Drug: Molindone<br>* oral molindone from 10-140mg/daily for up to 52 weeks<br>* Other names: Moban;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at 8 Weeks | Assessed with the Positive and Negative Syndrome Scale in which a clinician rates various psychotic symptoms on the basis of observation of the participant, interview with the participant, and review of all other available information including informant reports. The scale consists of 30 items which are rated categorically between 1 - no symptoms to 7 - extreme symptoms. The minimal score is 0 and the maximal score is 210, with higher scores reflecting more symptoms. Typically scores > that 60 are considered clinically significant. | 8 weeks | 
| Change From Baseline in PANSS Positive Symptom Subscale Score at 8 Weeks. | The PANSS (described above) includes 7 items that reflect positive psychotic symptoms such as hallucinations and delusions. As are all items within the PANSS, items are categorically rated by the clinician between 0 - no symptoms to 7 extreme symptoms. The minimal score is 0 reflecting no positive symptoms to 49 reflecting that all items were extreme. Higher scores reflect more severe symptoms. Scores above 18 are usually clinically significant. | 8 weeks | 
| Change From Baseline in PANSS Negative Symptom Subscale at Week 8 | The PANSS (described above) includes 7 items that reflect negative psychotic symptoms such as amotivation and social withdrawal. As are all items within the PANSS, items are categorically rated by the clinician between 0 - no symptoms to 7 extreme symptoms. The minimal score is 0 reflecting no positive symptoms to 49 reflecting that all items were extreme. Higher scores reflect more severe symptoms. Scores above 18 are usually clinically significant. | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Weight at Week 8 | change in weight from baseline to week 8 in kg | 8 weeks | 
| Change From Baseline in Barnes Akathisia Scale at Week 8 | Barnes Akathisia Scale is a clinician rated scale which considers information based on observation of the participant as well as participant report. The scale includes 3 items rated between 0- none to 3 severe and 1 summary item rated between 0 none to 5 severe. All items are summed to obtain the total score. The minimal total score is 0 and the maximal score is 14 with higher scores reflecting more severe akathisia. A score of 4 or more is clinically significant. | 8 weeks | 
| Change From Baseline in Body Mass Index Change, kg/m2, at Week 8 | Change from baseline in Body Mass Index Change, kg/m2, at week 8, last observation was carried forward for individuals who withdrew from treatment early. | 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Psychotic Disorders, Schizophreniform Disorder