Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 31 of 1552 for:    child psychiatry

Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00001656
Recruitment Status : Completed
First Posted : November 4, 1999
Results First Posted : April 12, 2011
Last Update Posted : April 12, 2011
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)

Tracking Information
First Submitted Date  ICMJE November 3, 1999
First Posted Date  ICMJE November 4, 1999
Results First Submitted Date  ICMJE March 2, 2011
Results First Posted Date  ICMJE April 12, 2011
Last Update Posted Date April 12, 2011
Study Start Date  ICMJE June 1997
Actual Primary Completion Date June 2008   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 11, 2011)
  • Change in the Scale for the Assessment of Negative Symptoms [ Time Frame: 8 week double-blind study period; baseline and 8 weeks ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    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 ]
    Measures change in the severity of anxiety; Minimum score = 0; maximum score = 7; lower score is considered a better outcome.
Original Primary Outcome Measures  ICMJE Not Provided
Change History Complete list of historical versions of study NCT00001656 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders
Official Title  ICMJE Childhood Onset Psychotic Disorders: Characterization and Treatment With Atypical Neuroleptics
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Childhood Schizophrenia
  • Psychotic Disorder
  • Schizophrenia
Intervention  ICMJE
  • Drug: Olanzapine
    tablet; 5-20mg/day; 8 weeks
    Other Name: "Zyprexa"
  • Drug: Clozapine
    tablet; 12.5-900mg/day; 8 weeks
    Other Name: "Clozaril"
Study Arms  ICMJE
  • Active Comparator: Olanzapine
    Intervention: Drug: Olanzapine
  • Active Comparator: Clozapine
    Intervention: Drug: Clozapine
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: March 11, 2011)
25
Original Enrollment  ICMJE
 (submitted: June 23, 2005)
40
Actual Study Completion Date  ICMJE June 2008
Actual Primary Completion Date June 2008   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE
  • 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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 7 Years to 18 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00001656
Other Study ID Numbers  ICMJE 970126
97-M-0126
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Judith L. Rapoport, M.D./National Institute of Mental Health, National Institutes of Health
Study Sponsor  ICMJE National Institute of Mental Health (NIMH)
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Judith L Rapoport, M.D. Child Psychiatry Branch, NIMH, NIH
PRS Account National Institutes of Health Clinical Center (CC)
Verification Date March 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP