Clinical trial NCT00053703: Treatment of Early Onset Schizophrenia Spectrum Disorders (TEOSS)
Official title: Treatment of Schizophrenia and Related Disorders in Children and Adolescents
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Schizophrenia
Keywords: Psychotic Disorders
Schizophreniform Disorder
Lead sponsor: University of North Carolina, Chapel Hill
Sponsor class: OTHER
Collaborators: name: National Institute of Mental Health (NIMH)
First posted: 2003-02-05
Enrollment: 116
Sex: ALL
Minimum age (years): 8
Maximum age (years): 19
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Change From Baseline in Positive and Negative Syndrome Scale (PANSS) Total Score at 8 Weeks
timeFrame: 8 weeks
measure: Change From Baseline in PANSS Positive Symptom Subscale Score at 8 Weeks.
timeFrame: 8 weeks
measure: Change From Baseline in PANSS Negative Symptom Subscale at Week 8
timeFrame: 8 weeks
Secondary outcomes:
measure: Change From Baseline in Weight at Week 8
timeFrame: 8 weeks
measure: Change From Baseline in Barnes Akathisia Scale at Week 8
timeFrame: 8 weeks
measure: Change From Baseline in Body Mass Index Change, kg/m2, at Week 8
timeFrame: 8 weeks
Other outcomes:
Locations:
city: Medford
country: United States
facility: Cambridge Health Alliance
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals of Cleveland
state: Ohio
city: Seattle
country: United States
facility: University of Washington
state: Washington
Study officials:
affiliation: University of North Carolina, Chapel Hill
name: Linmarie Sikich, M.D.
role: STUDY_CHAIR
References:
citation: McCLELLAN J, Sikich L, Findling RL, Frazier JA, Vitiello B, Hlastala SA, Williams E, Ambler D, Hunt-Harrison T, Maloney AE, Ritz L, Anderson R, Hamer RM, Lieberman JA. Treatment of early-onset schizophrenia spectrum disorders (TEOSS): rationale, design, and methods. J Am Acad Child Adolesc Psychiatry. 2007 Aug;46(8):969-978. doi: 10.1097/CHI.0b013e3180691779.
citation: Frazier JA, McCLELLAN J, Findling RL, Vitiello B, Anderson R, Zablotsky B, Williams E, McNAMARA NK, Jackson JA, Ritz L, Hlastala SA, Pierson L, Varley JA, Puglia M, Maloney AE, Ambler D, Hunt-Harrison T, Hamer RM, Noyes N, Lieberman JA, Sikich L. Treatment of early-onset schizophrenia spectrum disorders (TEOSS): demographic and clinical characteristics. J Am Acad Child Adolesc Psychiatry. 2007 Aug;46(8):979-988. doi: 10.1097/chi.0b013e31807083fd.
citation: Findling RL, Johnson JL, McClellan J, Frazier JA, Vitiello B, Hamer RM, Lieberman JA, Ritz L, McNamara NK, Lingler J, Hlastala S, Pierson L, Puglia M, Maloney AE, Kaufman EM, Noyes N, Sikich L. Double-blind maintenance safety and effectiveness findings from the Treatment of Early-Onset Schizophrenia Spectrum (TEOSS) study. J Am Acad Child Adolesc Psychiatry. 2010 Jun;49(6):583-94; quiz 632. doi: 10.1016/j.jaac.2010.03.013. Epub 2010 May 1.
citation: Taylor JH, Appel S, Eli M, Alexander-Bloch A, Maayan L, Gur RE, Bloch MH. Time to Clinical Response in the Treatment of Early Onset Schizophrenia Spectrum Disorders Study. J Child Adolesc Psychopharmacol. 2021 Feb;31(1):46-52. doi: 10.1089/cap.2020.0030. Epub 2020 Jul 1.
citation: Taylor JH, Jakubovski E, Gabriel D, Bloch MH. Predictors and Moderators of Antipsychotic-Related Weight Gain in the Treatment of Early-Onset Schizophrenia Spectrum Disorders Study. J Child Adolesc Psychopharmacol. 2018 Sep;28(7):474-484. doi: 10.1089/cap.2017.0147. Epub 2018 Jun 19.
citation: Gabriel D, Jakubovski E, Taylor JH, Artukoglu BB, Bloch MH. Predictors of treatment response and drop out in the Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS) study. Psychiatry Res. 2017 Sep;255:248-255. doi: 10.1016/j.psychres.2017.05.038. Epub 2017 May 30.
citation: Frazier JA, Giuliano AJ, Johnson JL, Yakutis L, Youngstrom EA, Breiger D, Sikich L, Findling RL, McClellan J, Hamer RM, Vitiello B, Lieberman JA, Hooper SR. Neurocognitive outcomes in the Treatment of Early-Onset Schizophrenia Spectrum Disorders study. J Am Acad Child Adolesc Psychiatry. 2012 May;51(5):496-505. doi: 10.1016/j.jaac.2012.02.001. Epub 2012 Mar 13.
citation: Sikich L, Frazier JA, McClellan J, Findling RL, Vitiello B, Ritz L, Ambler D, Puglia M, Maloney AE, Michael E, De Jong S, Slifka K, Noyes N, Hlastala S, Pierson L, McNamara NK, Delporto-Bedoya D, Anderson R, Hamer RM, Lieberman JA. Double-blind comparison of first- and second-generation antipsychotics in early-onset schizophrenia and schizo-affective disorder: findings from the treatment of early-onset schizophrenia spectrum disorders (TEOSS) study. Am J Psychiatry. 2008 Nov;165(11):1420-31. doi: 10.1176/appi.ajp.2008.08050756. Epub 2008 Sep 15.