Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders

NCT00001656 | Completed Phase 4 Results

• 2 other identifiers: 97012697-M-0126
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to compare the effectiveness and side effects of the drugs clozapine and olanzapine in children and adolescents with schizophrenia and psychoses. Childhood psychosis is a serious disorder that may have devastating consequences. Effective treatments for the condition are under continual investigation. This study will examine the causes of and offer treatment for childhood psychosis. Participants in this study will undergo psychological tests, blood and urine tests, electroencephalogram (EEG), electrocardiogram (EKG), and magnetic resonance imaging (MRI) scans of the brain for the first 1 to 2 weeks of the study while taking their regular medications. Participants will then be tapered off their medications over 1 to 3 weeks and will continue to stay off medications for an additional 2 days to 3 weeks. During this time, participants will undergo psychiatric, neurological, and cardiac examinations as well as blood tests. After this period without medications, participants will be randomly assigned to receive either clozapine or olanzapine for 8 weeks. An EEG will be performed prior to treatment and after 6 weeks of study medication. Participants who respond well to the study drugs may continue to receive them through their own physician. Participants who do not respond to either clozapine or olanzapine or cannot tolerate their side effects will be treated individually with other drugs until optimum treatment is identified. Regular telephone updates and in person visits to NIH for repeat testing and MRIs will be conducted.

Conditions

Childhood Schizophrenia; Psychotic Disorder; Schizophrenia

Keywords

Clozapine; Olanzapine; Drug Response; Safety; Childhood Onset Schizophrenia; Schizoaffective Disorder; Multidimensionally Impaired Syndrome; Phenomenology; Biochemical Correlates; Brain Imaging; Schizophrenia; Childhood Schizophrenia; Psychosis

Outcome Measures

Primary Outcomes (8)

• Change in the Scale for the Assessment of Negative Symptoms

  Measures change in affective flattening or blunting, alogia, avolition/apathy, anhedonia/asociality, attention; minimum score = 0; maximum score = 125; lower values are considered a better outcome

  8 week double-blind study period; baseline and 8 weeks

• Change in the Clinical Global Impression Severity of Symptoms Scale

  Measures change in the severity of symptoms; Minimum score = 1; maximum score = 7; lower score is considered a better outcome.

  8 week double-blind study period; baseline and 8 weeks

• Change in the Brief Psychiatric Rating Scale-24

  A 24-item scale measuring change in interpersonal behaviors, mood, psychosis, anxiety, speech, sleep, orientation and physical activity. Lowest score = 24; highest score = 168; lower score is considered a better outcome.

  8 week double-blind study period; baseline and 8 weeks

• Change in the Scale for the Assessment of Positive Symptoms

  Measures change in hallucinations, delusions, bizarre behavior, and thought organization. Minimum score = 0; maximum score = 170; lower score is considered a better outcome.

  8 week double-blind study period; baseline and 8 weeks

• Change in the Bunney-Hamburg Rating Scale for Psychosis

  Measures change in psychosis severity; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.

  8 week double-blind study period; baseline and 8 weeks

• Change in Bunney-Hamburg Rating Scale for Depression

  Measures change in severity of depression; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.

  8 week double-blind study period; baseline and 8 weeks

• Change in Bunney-Hamburg Rating Scale for Mania

  Measures change in the severity of mania; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.

  8 week double-blind study period; baseline and 8 weeks

• Change in the Bunney-Hamburg Rating Scale for Anxiety

  Measures change in the severity of anxiety; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.

  8 week double-blind study period; baseline and 8 weeks

Other Outcomes (4)

• Change in Weight

  8 week double-blind study period; baseline and 8 weeks

• Change in Body Mass Index (BMI)

  8 week double-blind study period; baseline and 8 weeks

• Change in Extrapyramidal Movements as Measured by the Abnormal Involuntary Movements Scale (AIMS)

  8 week double-blind study period; baseline and 8 weeks

Study Arms (2)

Olanzapine

ACTIVE COMPARATOR

Drug: Olanzapine

Clozapine

ACTIVE COMPARATOR

Drug: Clozapine

Interventions

Olanzapine DRUG

tablet; 5-20mg/day; 8 weeks

Also known as: "Zyprexa"

Olanzapine

Clozapine DRUG

tablet; 12.5-900mg/day; 8 weeks

Also known as: "Clozaril"

Clozapine

Eligibility Criteria

• Age: 7 Years - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• Males and females, age 7 to 18 years
• Onset of psychotic symptoms before 13th birthday and a DSM-IV diagnosis of either schizophrenia, schizoaffective disorder, MDI syndrome, or psychosis NOS (not otherwise specified).
• Current significant impairment due to the illness (current psychotic symptoms, decline of functioning academically and socially, significant discomfort due to psychotic symptoms).
• Failure of two prior trials with antipsychotic medications (either typical or atypical) used at adequate doses (greater than or equal to 100 mg/day in chlorpromazine equivalents) and for adequate duration (at least 4 weeks, unless terminated due to intolerable side effects). Failure is defined as either insufficient response with persistence of symptoms significantly impairing child's functioning, according to child's and parental reports and medical and school records, or intolerable side effects to drugs other than clozapine and olanzapine.
• Subjects may be included if their previous trial(s) of olanzapine failed to reach the dose of 20. mg/day or a duration of fewer than four weeks.
• Subjects may be included if their previous trial(s) of clozapine failed to reach the dose of 200. mg/day or a duration of fewer than six weeks.
• Comorbid psychiatric disorders in the past 12 months are permitted as long as not clinically significant.

You may not qualify if:

• Prepsychotic full-scale IQ less than 70.
• Unstable major neurological or medical conditions.
• Current pregnancy or plan to become pregnant during the first three months (the duration of the study) in woman of childbearing age; breast-feeding in woman with infants.
• DSM-IV substance abuse or dependence in the past 6 months.
• True non-responders to either olanzapine or clozapine. True non-response is defined as: a) intolerance to either of the medications preventing an adequate trial, or b) only minimal (less than 20%) benefit with the adequate trial of either of the medications. Adequate trial constitutes at least 8 weeks of the medication with the dose of 20 mg on olanzapine or 200 mg of clozapine.

Sponsors & Collaborators

• National Institute of Mental Health (NIMH): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Gordon CT, Frazier JA, McKenna K, Giedd J, Zametkin A, Zahn T, Hommer D, Hong W, Kaysen D, Albus KE, et al. Childhood-onset schizophrenia: an NIMH study in progress. Schizophr Bull. 1994;20(4):697-712. doi: 10.1093/schbul/20.4.697.

  PMID: 7701277 BACKGROUND

• Nicolson R, Rapoport JL. Childhood-onset schizophrenia: rare but worth studying. Biol Psychiatry. 1999 Nov 15;46(10):1418-28. doi: 10.1016/s0006-3223(99)00231-0.

  PMID: 10578456 BACKGROUND

• Shaw P, Sporn A, Gogtay N, Overman GP, Greenstein D, Gochman P, Tossell JW, Lenane M, Rapoport JL. Childhood-onset schizophrenia: A double-blind, randomized clozapine-olanzapine comparison. Arch Gen Psychiatry. 2006 Jul;63(7):721-30. doi: 10.1001/archpsyc.63.7.721.

  PMID: 16818861 RESULT

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Schizophrenia, Childhood; Psychotic Disorders; Schizophrenia

Interventions

Olanzapine; Clozapine

Condition Hierarchy (Ancestors)

Neurodevelopmental Disorders; Mental Disorders; Schizophrenia Spectrum and Other Psychotic Disorders

Intervention Hierarchy (Ancestors)

Benzodiazepines; Benzazepines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dibenzazepines; Heterocyclic Compounds, 3-Ring

Results Point of Contact

• Title: Judith L. Rapoport, M.D.
• Organization: National Institute of Mental Health

rapoporj@mail.nih.gov

301-496-6080

Study Officials

• Judith L Rapoport, M.D.

  Child Psychiatry Branch, NIMH, NIH

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH

Study Record Dates

• First Submitted: November 3, 1999
• First Posted: November 4, 1999
• Study Start: June 1, 1997
• Primary Completion: June 1, 2008
• Study Completion: June 1, 2008
• Last Updated: April 12, 2011
• Results First Posted: April 12, 2011

Record last verified: 2011-03

Locations

US (1)