Childhood SchizophreniaPhase 4NCT00001656

Comparison of Clozapine vs Olanzapine in Childhood-Onset Psychotic Disorders

A Phase 4 study testing Olanzapine and Clozapine in people with Childhood Schizophrenia and Psychotic Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial 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. Read more about this study

Who is it for?: Ages 7 to 18 years
Conditions the study is for: Childhood Schizophrenia, Psychotic Disorder, Schizophrenia
What is being tested?: Olanzapine and Clozapine
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 25 participants
Where: 1 siteUnited States
Study dates: Jun 1997to Jun 2008
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 7 to 18 years
All sexes
No healthy volunteers
Child, Adult

Who may be able to join

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.

Who cannot join

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.

Trial locations and contacts

1 site in 1 country.

United States1 site

National Institutes of Health Clinical Center, 9000 Rockville Pike
Bethesda, Maryland, 20892

Other trials in United States

About this study

Official title: Childhood Onset Psychotic Disorders: Characterization and Treatment With Atypical Neuroleptics

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.

Read the 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.

Conditions: Childhood Schizophrenia, Psychotic Disorder, Schizophrenia
Being tested: Olanzapine, Clozapine
Keywords: Clozapine, Olanzapine, Drug Response, Safety, Childhood Onset Schizophrenia, Schizoaffective Disorder, Multidimensionally Impaired Syndrome, Phenomenology, Biochemical Correlates, Brain Imaging, Schizophrenia, Childhood Schizophrenia, Psychosis
Medical subject headings: Schizophrenia, Childhood, Psychotic Disorders, Schizophrenia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

OlanzapineDrug
Also called "Zyprexa"
tablet; 5-20mg/day; 8 weeks
ClozapineDrug
Also called "Clozaril"
tablet; 12.5-900mg/day; 8 weeks

Study groups in NCT00001656
Study group	Role	What they receive
Olanzapine	Active comparator	Not described Receives: Drug: Olanzapine
Clozapine	Active comparator	Not described Receives: Drug: Clozapine

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 8 week double-blind study period; baseline and 8 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jun 1997Jun 2008

First posted4 Nov 1999 (estimated)
Study startJun 1997
Primary completionJun 2008
Study completionJun 2008

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (3)Papers the sponsor has linked to this study.
Other trials for Childhood SchizophreniaStudies of the same condition, open and under way.
More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind
Who is masked: Participant, Care provider, Investigator
Enrolment: 25 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00001656
Sponsor's protocol ID: 970126
Other IDs: 97-M-0126
Status last verified: Mar 2011
First submitted: 3 Nov 1999
Last updated: 12 Apr 2011
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No

Publications

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.
PubMed 7701277
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.
PubMed 10578456
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.
PubMed 16818861

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Childhood Schizophrenia trials

Study at a glance

From the registry record, last updated by the sponsor on 12 Apr 2011. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Childhood Onset Psychotic Disorders: Characterization and Treatment With Atypical Neuroleptics
ClinicalTrials.gov ID: NCT00001656
Acronym / sponsor ID: 970126
Conditions: Childhood Schizophrenia, Psychotic Disorder, Schizophrenia
Keywords: Clozapine, Olanzapine, Drug Response, Safety, Childhood Onset Schizophrenia, Schizoaffective Disorder, Multidimensionally Impaired Syndrome, Phenomenology
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 25 participants (actual)
Lead sponsor: National Institute of Mental Health (NIMH)US National Institutes of Health
Study start: Jun 1997
Primary completion: Jun 2008 (actual)
Study completion: Jun 2008 (actual)
First posted: 4 Nov 1999 (estimated)
Results: Posted 12 Apr 2011

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

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.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Triple blind (participant, care provider, investigator)
Number of arms: 2

Arm	Type	Receives
Olanzapine	Active comparator	Drug: Olanzapine
Clozapine	Active comparator	Drug: Clozapine

Who may qualify

Ages: 7 to 18 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Child, Adult

Key inclusion criteria (7 listed)

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.

Key exclusion criteria (5 listed)

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.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
OlanzapineAlso: "Zyprexa"tablet; 5-20mg/day; 8 weeks	Drug	Olanzapine
ClozapineAlso: "Clozaril"tablet; 12.5-900mg/day; 8 weeks	Drug	Clozapine

Primary outcome

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.

Results and safety

Results posted to the registry on 12 Apr 2011, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Olanzapine Group	13	12
Clozapine Group	12	12

Primary outcome: Change in the Scale for the Assessment of Negative Symptoms

Time frame: 8 week double-blind study period; baseline and 8 weeks. Mean (95% Confidence Interval). Unit: Scores on a scale

Measure	Olanzapine Group n = 13	Clozapine Group n = 12
Value	-14 (-20 to -7)	-25 (-34 to -15)

Olanzapine Group vs Clozapine Group: p = .04, ANCOVA

Primary outcome: Change in the Clinical Global Impression Severity of Symptoms Scale

Time frame: 8 week double-blind study period; baseline and 8 weeks. Mean (95% Confidence Interval). Unit: Scores on a scale

Measure	Olanzapine Group n = 13	Clozapine Group n = 12
Value	-0.6 (-1.3 to 0.1)	-1.6 (-2.3 to -0.8)

Olanzapine Group vs Clozapine Group: p = 0.21, ANCOVA

Primary outcome: Change in the Brief Psychiatric Rating Scale-24

Time frame: 8 week double-blind study period; baseline and 8 weeks. Mean (95% Confidence Interval). Unit: Scores on a scale

Measure	Olanzapine Group n = 13	Clozapine Group n = 12
Value	-13 (-21 to -6)	-19 (-26 to -12)

Olanzapine Group vs Clozapine Group: p = 0.35, ANCOVA

Primary outcome: Change in the Scale for the Assessment of Positive Symptoms

Time frame: 8 week double-blind study period; baseline and 8 weeks. Mean (95% Confidence Interval). Unit: Scores on a scale

Measure	Olanzapine Group n = 13	Clozapine Group n = 12
Value	-7 (-18 to 5)	-21 (-33 to -9)

Olanzapine Group vs Clozapine Group: p = 0.19, ANCOVA

Adverse events

Time frame: 8 week-double-blind study period. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Olanzapine Group	1 of 13 (7.7%)	13 of 13 (100%)	Not reported
Clozapine Group	2 of 12 (16.7%)	12 of 12 (100%)	Not reported

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2011.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Background: PubMed 7701277Gordon 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.
Background: PubMed 10578456Nicolson 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.
Results publication: PubMed 16818861Shaw 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.
NIH Clinical Center Detailed Web PageLink provided by the sponsor.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Judith L Rapoport, M.D. principal investigator

Child Psychiatry Branch, NIMH, NIH

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Olanzapine and Clozapine in people with Childhood Schizophrenia and Psychotic Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Apr 2011. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 12 Apr 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in the Scale for the Assessment of Negative Symptoms (time frame: 8 week double-blind study period; baseline and 8 weeks). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00001656, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2011.