Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00001656
First received: November 3, 1999
Last updated: March 11, 2011
Last verified: March 2011
  Purpose

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.


Condition Intervention Phase
Childhood Schizophrenia
Psychotic Disorder
Schizophrenia
Drug: Olanzapine
Drug: Clozapine
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Childhood Onset Psychotic Disorders: Characterization and Treatment With Atypical Neuroleptics

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • Change in the Scale for the Assessment of Negative Symptoms [ Time Frame: 8 week double-blind study period; baseline and 8 weeks ] [ Designated as safety issue: No ]
    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

  • Change in the Clinical Global Impression Severity of Symptoms Scale [ Time Frame: 8 week double-blind study period; baseline and 8 weeks ] [ Designated as safety issue: No ]
    Measures change in the severity of symptoms; Minimum score = 1; maximum score = 7; lower score is considered a better outcome.

  • Change in the Brief Psychiatric Rating Scale-24 [ Time Frame: 8 week double-blind study period; baseline and 8 weeks ] [ Designated as safety issue: No ]
    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.

  • Change in the Scale for the Assessment of Positive Symptoms [ Time Frame: 8 week double-blind study period; baseline and 8 weeks ] [ Designated as safety issue: No ]
    Measures change in hallucinations, delusions, bizarre behavior, and thought organization. Minimum score = 0; maximum score = 170; lower score is considered a better outcome.

  • Change in the Bunney-Hamburg Rating Scale for Psychosis [ Time Frame: 8 week double-blind study period; baseline and 8 weeks ] [ Designated as safety issue: No ]
    Measures change in psychosis severity; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.

  • Change in Bunney-Hamburg Rating Scale for Depression [ Time Frame: 8 week double-blind study period; baseline and 8 weeks ] [ Designated as safety issue: No ]
    Measures change in severity of depression; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.

  • Change in Bunney-Hamburg Rating Scale for Mania [ Time Frame: 8 week double-blind study period; baseline and 8 weeks ] [ Designated as safety issue: No ]
    Measures change in the severity of mania; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.

  • Change in the Bunney-Hamburg Rating Scale for Anxiety [ Time Frame: 8 week double-blind study period; baseline and 8 weeks ] [ Designated as safety issue: No ]
    Measures change in the severity of anxiety; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.


Enrollment: 25
Study Start Date: June 1997
Study Completion Date: June 2008
Primary Completion Date: June 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Olanzapine Drug: Olanzapine
tablet; 5-20mg/day; 8 weeks
Other Name: "Zyprexa"
Active Comparator: Clozapine Drug: Clozapine
tablet; 12.5-900mg/day; 8 weeks
Other Name: "Clozaril"

Detailed Description:

The purpose of this protocol is to compare efficacy of clozapine and olanzapine in children and adolescents with schizophrenia and psychoses, as well as to learn about side effects of these medication in pediatric population. The underlying hypothesis is that clozapine has superior efficacy over olanzapine.

Children and adolescents, ages 7 to 18 years, meeting DSM-IV criteria for schizophrenia, schizoaffective disorder and psychotic disorder not otherwise specified, with onset of psychosis before their 13th birthday, who have not responded to at least two prior trials with typical or a typical neuroleptics, will be eligible to participate in a double-blind, parallel group, trial of olanzapine-clozapine.

This study will be done in conjunction with the Screening protocol, which will include characterization by clinical phenomenology, eye tracking, MRI brain imaging, plasma biochemistry, and chromosomal analysis.

This study will consist of the following phases 1) Tapering of psychotropic medications (1-4 weeks, depending upon type and dosage). 2) Observation for up to 2 weeks drug free, in order to establish a baseline prior to starting medication trial. 3) An 8 week double-blind trial of either clozapine or olanzapine. Efficacy and tolerability of clozapine and olanzapine will be compared using specified criteria. 4) If desired improvement not achieved or trial is interrupted, an 8 week open trial of the second medication and 5) Discharge following medication optimization for up to 4 weeks, or as clinically appropriate. This protocol also includes a follow-up every 2 to 3 years for a period of 10 years.

  Eligibility

Ages Eligible for Study:   7 Years to 18 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • INCLUSION CRITERIA:

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.

EXCLUSION CRITERIA:

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00001656

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
Investigators
Principal Investigator: Judith L Rapoport, M.D. Child Psychiatry Branch, NIMH, NIH
  More Information

Additional Information:
Publications:
Responsible Party: Judith L. Rapoport, M.D./National Institute of Mental Health, National Institutes of Health
ClinicalTrials.gov Identifier: NCT00001656     History of Changes
Other Study ID Numbers: 970126, 97-M-0126
Study First Received: November 3, 1999
Results First Received: March 2, 2011
Last Updated: March 11, 2011
Health Authority: United States: Institutional Review Board
United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Clozapine
Olanzapine
Drug Response
Safety
Childhood Onset Schizophrenia
Schizoaffective Disorder
Multidimensionally Impaired Syndrome
Phenomenology
Biochemical Correlates
Brain Imaging
Schizophrenia
Childhood Schizophrenia
Psychosis

Additional relevant MeSH terms:
Psychotic Disorders
Mental Disorders
Schizophrenia
Schizophrenia, Childhood
Schizophrenia and Disorders with Psychotic Features
Mental Disorders Diagnosed in Childhood
Clozapine
Olanzapine
Serotonin Antagonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Central Nervous System Agents
Therapeutic Uses
Psychotropic Drugs
GABA Antagonists
GABA Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014