Clozapine vs. Placebo in Treatment-Refractory Bipolar Disorder in Children and Adolescents
Information source: National Institutes of Health Clinical Center (CC)
ClinicalTrials.gov processed this data on August 20, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Bipolar Disorder
Intervention: Clozapine (Drug)
Phase: Phase 3
Status: Completed
Sponsored by: National Institute of Mental Health (NIMH)
Summary
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.
Clinical Details
Official title: Clozapine vs Placebo In Treatment-Refractory Bipolar Disorder In Children And Adolescents
Study design: Endpoint Classification: Efficacy Study, Primary Purpose: Treatment
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
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
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).
Locations and Contacts
National Institute of Mental Health (NIMH), Bethesda, Maryland 20892, United States
Additional Information
Related publications: Wozniak J, Biederman J, Kiely K, Ablon JS, Faraone SV, Mundy E, Mennin D. Mania-like symptoms suggestive of childhood-onset bipolar disorder in clinically referred children. J Am Acad Child Adolesc Psychiatry. 1995 Jul;34(7):867-76. Geller B, Sun K, Zimerman B, Luby J, Frazier J, Williams M. Complex and rapid-cycling in bipolar children and adolescents: a preliminary study. J Affect Disord. 1995 Aug 18;34(4):259-68. Faedda GL, Baldessarini RJ, Suppes T, Tondo L, Becker I, Lipschitz DS. Pediatric-onset bipolar disorder: a neglected clinical and public health problem. Harv Rev Psychiatry. 1995 Nov-Dec;3(4):171-95. Review.
Starting date: May 2002
Last updated: March 3, 2008
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