Clinical trial NCT00622739: Ziprasidone in Pediatric Bipolar Disorder
Official title: Ziprasidone in Pediatric Bipolar Disorder: a 6-week, Open-label Comparison of Rapid vs. Slow Dose Titration
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bipolar Disorder
Keywords: Bipolar Disorder
Children
Adolescents
Treatment
Lead sponsor: Baylor College of Medicine
Sponsor class: OTHER
Collaborators: name: Stanley Medical Research Institute
name: Pfizer
name: Children's Medical Center Dallas
First posted: 2008-02-25
Enrollment: 28
Sex: ALL
Minimum age (years): 10
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This is a 6 week, open-label, blinded-rater, randomized, controlled, pilot study designed to determine the dosing, safety and efficacy of ziprasidone in the treatment of pediatric bipolar disorder (PBD). In this pilot study we are comparing the efficacy of rapid versus slow dose titration of ziprasidone in PBD. The investigators hypothesize that subjects on ziprasidone monotherapy will have a reduction in manic symptoms. Also, the investigators hypothesize that slower titration of ziprasidone will result in lesser side effects which will assist in medication compliance as measured by patient report and pill count.

Detailed description: This study will enroll approximately 60 children and adolescents aged 10-17 years who have been diagnosed with bipolar disorder. Their participation will last about 8 weeks (2 weeks of screening and 6 weeks of medication management) and enrollment will last for two years. After the screening period, all subjects who meet inclusion/exclusion criteria will be randomized to either rapid or slow dose titration of ziprasidone. Subjects in the rapid titration group will reach their maximum dose of study drug over 2 weeks, subjects in the slow titration group over 4 weeks. The study doctor may deviate from the dosing schedule if clinically indicated. The primary data analysis of this pilot study will examine the effect of rapid- versus slow-dose titration of ziprasidone on manic symptoms.

Eligibility criteria: Inclusion Criteria:

* Outpatients aged 10-17 years
* Currently meet Diagnostic and Statistical Manual of Mental Disorders IV-Text Revision (DSM-IV-TR) criteria for bipolar disorder, type I, II or Not Otherwise Specified (NOS) as determined by the Schedule for Affective Disorders and Schizophrenia -Present/Lifetime (Kiddie-SADS-PL)
* Experiencing manic, hypomanic or mixed states as determined by clinical diagnosis and Kiddie- Young Mania rating scale (K-YMRS) equal to or more than 14
* General good health as determined by medical history, physical examination, and laboratory evaluations
* Female adolescents, if sexually active, must practice birth control methods approved by the primary investigator
* Ability to swallow tablets
* Subject's parent or guardian must be fully capable of monitoring the subject's disease process and compliance to treatment
* Parent(s) or legal guardian(s) must read and sign the informed consent form after the nature of the study has been fully explained and assent must be obtained from subjects.

Exclusion Criteria:

* Have a lifetime DSM-IV-TR Axis I disorder diagnosis of autistic disorder, schizophrenia, schizoaffective disorder, or other psychotic disorders
* DSM-IV-TR diagnosis of alcohol or substance abuse or dependence within the past 6 months
* Serious or unstable medical or neurological conditions which require concomitant medications
* Judged by the principal investigator (PI) to be acutely suicidal or homicidal, or at imminent risk of injuring self or others or causing significant damage to property-i.e., subject needs to be in an inpatient facility
* Known or suspected intelligence quotient (IQ) less than 70
* Have a DSM-IV-TR diagnosis of anorexia and/or bulimia at the time of screening or within the last six months
* Female who is pregnant or nursing
* Subjects with a history of syncopal episodes (sudden loss of consciousness with loss of postural tone and not preceded by a pre-syncopal phase) or unexplained loss of consciousness
* Subjects with a history of significant cardiovascular disease or significant concurrent cardiovascular disease, including uncontrolled hypertension, hypotension, congestive heart failure or congenital heart disease
* Subjects with a history of cardiac arrhythmias, conduction abnormalities or known personal history or corrected QT prolongation (including congenital long QT syndrome)
* Subjects with a known genetic risk for QT syndrome determined by family history in first degree relatives
* Subjects taking any medications known to interact with ziprasidone or subjects taking any medications which have been consistently observed to prolong the QT interval
* Subjects with a clinically significant ECG abnormality at screening
* Subjects with persistent QTc (Fridericia) \* 460 msec at screening
* Screening laboratory values outside the normal range and judged to be clinically significant by the investigator
* Patients and families that are Spanish speaking only will be excluded from the study as some instruments used in the study have not been validated in Spanish

Primary outcomes:
measure: Young Mania Rating Scale (YMRS)
timeFrame: 6 weeks of treatment
Secondary outcomes:
measure: Children's Depression Rating Scale
timeFrame: 6 weeks of treatment
measure: Clinical Global Impressions-Severity (CGI-S) Scale
timeFrame: 6 weeks of treatment
measure: SAFTEE (Side Effects Rating Scale)
timeFrame: 6 weeks of treatment
measure: AIMS (Abnormal Involuntary Movement Scale)
timeFrame: 6 weeks of treatment
measure: Barnes Akathisia Rating Scale (BARS)
timeFrame: 6 weeks of treatment
Other outcomes:
Locations:
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
Study officials:
affiliation: UT Southwestern Medical Center
name: Kirti Saxena, MD
role: PRINCIPAL_INVESTIGATOR
References: