Clozapine vs. Placebo in Treatment-Refractory Bipolar Disorder in Children and Adolescents

This study has been completed.
Sponsor:
Information provided by:
National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov Identifier:
NCT00036582
First received: May 10, 2002
Last updated: March 3, 2008
Last verified: February 2004
  Purpose

The purpose of this study is to determine the safety and effectiveness of clozapine in children and adolescents with treatment resistant bipolar disorder. This study will also explore how the brain functions in early-onset bipolar disorder.


Condition Intervention Phase
Bipolar Disorder
Drug: Clozapine
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Primary Purpose: Treatment
Official Title: Clozapine vs Placebo In Treatment-Refractory Bipolar Disorder In Children And Adolescents

Resource links provided by NLM:


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

Estimated Enrollment: 116
Study Start Date: May 2002
Estimated Study Completion Date: February 2004
Detailed Description:

Bipolar disorder (BPD) in children and adolescents is a serious illness that carries a high risk for chronicity, impairing comorbidities, and completed suicide. Treatment options are often limited by inefficacy or intolerable side effects. Open trials in adult bipolar subjects and several case series in children and adolescents provide preliminary evidence that clozapine, an atypical antipsychotic, may be effective in treatment-resistant bipolar disorder. The first specific aim of this study is to test the efficacy and safety of clozapine compared to placebo in a double-blind study of children and adolescents with treatment refractory BPD. Other specific aims involve exploring the pathophysiology of early-onset BPD by 1) testing the hypotheses that, compared to controls, children with BPD have increased psychophysiological reactivity to emotional stimuli and decreased prepulse inhibition; 2) obtaining samples of genetic material from affected probands and their parents for later analysis; and 3) identifying anatomic changes in the brains of children with BPD using structural MRI.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

INCLUSION CRITERIA (All 5 must be met): Children with BPD

Ages 8-17

Currently meets criteria for bipolar disorder, manic or mixed, as determined by the K-SADS diagnostic interview.

Treatment-resistant, defined as a history of unsuccessful trials of lithium (documented level of greater than 0.8 mEq/L), valproic acid (documented level of greater than 50 ug/ml), carbamazepine (documented level greater than or equal to 6 ug/ml), a neuroleptic as well as a combination of two of these agents. Each trial must have been at least 6 weeks long. A trial will be considered unsuccessful if the medication was discontinued because of intolerable side-effects.

The child should be in treatment with a community psychiatrist to whom they will return upon completion of the study.

Current CGAS score less than 50

EXCLUSION CRITERIA: Children with BPD

Full scale IQ less than 80

Meets criteria for substance use disorder in the three months prior to randomization

Currently pregnant, lactating, or sexually active without using a barrier method of contraception

Previous treatment with clozapine

History of seizures

History of leukopenia or agranulocytosis

Presence of an unstable medical illness

INCLUSION CRITERIA: CONTROLS

Control subjects will be age- and sex- matched to the BPD subjects. They will have normal physical and neurological examinations, and an identified primary care physician. Both control subjects and their first-degree relatives must be free of current or past psychopathology.

EXCLUSION CRITERIA: CONTROLS

I.Q less than 80; ongoing medical illness; neurologic disorder (including seizures); pregnancy; meeting past or present criteria for any diagnosis on the K-SADS-PL; meeting criterion A of post-traumatic stress disorder (exposure to a traumatic event).

  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00036582

Locations
United States, Maryland
National Institute of Mental Health (NIMH)
Bethesda, Maryland, United States, 20892
Sponsors and Collaborators
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00036582     History of Changes
Other Study ID Numbers: 020198, 02-M-0198
Study First Received: May 10, 2002
Last Updated: March 3, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institutes of Health Clinical Center (CC):
Psychophysiology
Structural MRI
Genetics
Bipolar Disorder
Children and Adolescents
Clozapine
Placebo
Treatment-Refractory
Bipolar
Healthy Volunteer
HV
BPD
Normal Control

Additional relevant MeSH terms:
Bipolar Disorder
Affective Disorders, Psychotic
Mood Disorders
Mental Disorders
Clozapine
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

ClinicalTrials.gov processed this record on April 16, 2014