Ziprasidone in Pediatric Bipolar Disorder

Phase 4

Completed

Conditions: Bipolar Disorder

Interventions: Drug: Ziprasidone

Registration Number: NCT00622739

Lead Sponsor: Baylor College of Medicine

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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 28

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
ziprasidone rapid dose	Ziprasidone	Rapid Dose Titration Group
ziprasidone slow dose	Ziprasidone	Slow Dose Titration Group

Primary Outcome Measures

Name	Time	Method
Young Mania Rating Scale (YMRS)	6 weeks of treatment	The Young Mania Rating Scale (YMRS) is a measure of the severity of manic symptoms. The scores on the scale range from 0-56. A score of more than or equal to 14 was the cut off for inclusion into this study. A higher score denotes increased severity of manic symptoms.

Secondary Outcome Measures

Name	Time	Method
AIMS (Abnormal Involuntary Movement Scale)	6 weeks of treatment	AIMS is a 12-item instrument assessing abnormal involuntary movements associated with antipsychotic drugs, such as tardive dystonia and chronic akathisia, as well as 'spontaneous' motor disturbance related to the illness itself. Scoring the AIMS consists of rating the severity of movement in three main anatomic areas (facial/oral, extremities, and trunk), based on a five-point scale (0=none, 4=severe).
Children's Depression Rating Scale	6 weeks of treatment	The CDRS-R is a 17 item clinician-rated instrument used to measure severity of depressive symptoms in youth (ages 6-18). Each item is rated on a 1 to 5 or 1 to 7 point scale, with a 1 describing absence of the given symptom. The CDRS-R yields a total score from 17 to 113 with a score of 40 or greater considered to symptomatic of depression. Scores of 35-40 indicate mild depression, 29-34 is borderline and \<28 is no depression.
Clinical Global Impressions-Severity (CGI-S) Scale	6 weeks of treatment	The CGI-S assesses clinical severity. The CGI-S is a seven point scale where 1 is the minimum value and 7 is the maximum value. Lower scores mean a better outcome. The CGI-Severity scale scores are: 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients.
SAFTEE (Side Effects Rating Scale)	6 weeks of treatment	The Systematic Assessment for Treatment of Emergent Events (SAFTEE) is one of the first comprehensive Adverse effects-elicitation instruments developed specifically for use in psychiatric clinical trials. The SAFTEE is a standardized method, which increases consistency of Adverse Effects data, both within and across clinical trials.It allows ratings of five levels of severity and collects information about the onset, duration, pattern, judgement of attribution of cause, and action taken by the clinician. Suggested probe questions are also provided, which the clinician can use to elicit detailed information about the AE. Furthermore, the SAFTEE requires the clinician to determine a time interval of inquiry to be used in the trial. Adverse Effects are graded as None=0, Mild=1, Moderate=2, Severe=3.
Barnes Akathisia Rating Scale (BARS)	6 weeks of treatment	The BARS measures drug-induced akathisia occurring specifically with use of neuroleptic agents. It is a four-item fully anchored scale. Three items (objective akathisia, subjective awareness of restlessness, and subjective distress related to restlessness) are rated on a 4-point scale (0= normal and 9= most severe) and, the global clinical assessment of akathisia uses a 5-point scale (0= normal and 4= most severe). Total scores ranged from 0-13 with higher scores reflecting more akathisia.