Clinical trial NCT00394095: Topiramate vs. Placebo in Preventing Weight Gain in Bipolar Disorder Treated With Olanzapine
Official title: A Double-Blind, Randomized, Placebo-Controlled, Pilot Study of Topiramate vs. Placebo in Combination With Olanzapine for the Prevention of Weight Gain in Manic or Mixed Youth With Bipolar Disorder
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Bipolar Disorder
Weight Gain
Keywords: Bipolar Disorder
Weight Gain
Lead sponsor: University of Cincinnati
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
First posted: 2006-10-31
Enrollment: 31
Sex: ALL
Minimum age (years): 10
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: The primary objective of this study is to examine the efficacy of topiramate in combination with olanzapine for the prevention of weight gain in youth with bipolar disorder. The secondary objective is to examine the tolerability of topiramate in combination with olanzapine for the prevention of weight gain in youth with bipolar disorder.

Detailed description: After consent and screening, patients will be initiated on 5mg or 10mg per day of olanzapine. Olanzapine doses will be titrated to 10-20 mg of olanzapine over one week, to a maximum of 20mg by day 21. Patients will also receive either topiramate (25mg bid titrated over 18 days to 150 mg bid. with flexibility to titrate to 200mg bid) or matched placebo. Topiramate will be initiated at a dose of 25 mg bid and will be increased by 25 mg bid every three days as tolerated. Patients will be evaluated by a blinded (to treatment status and adverse events) rater.

Eligibility criteria: Inclusion Criteria:

1. Male or female patients, ages 10-18 years.
2. Female patients of menarche must be using a medically accepted means of contraception (e.g. oral contraceptives, Depo-Provera, abstinence).
3. Each patient's authorized legal guardian must understand the nature of the study and must provide written informed consent. Each patient must also give assent to study participation.
4. Patients must have a diagnosis of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV-TR) bipolar disorder, type I and currently display an acute manic or mixed episode as determined by K-SADS (Geller et al 2000).
5. Patients must have a baseline (day 0) Young Mania Rating Scale score of at least 16.
6. Subjects should be fluent in English.

Exclusion Criteria:

1. Female patients who are either pregnant or lactating.
2. Clinically significant or unstable hepatic, renal, gastroenterologic, respiratory, cardiovascular, endocrinologic, immunologic, hematologic or other systemic medical conditions.
3. Any history of current or past diabetes that has been treated with pharmacological intervention.
4. Neurological disorders including epilepsy, stroke, or severe head trauma.
5. Clinically significant laboratory abnormalities (\> 3 times upper limit of normal), on any of the following tests: CBC with differential, electrolytes, BUN, creatinine, hepatic transaminases, lipid profile, fasting glucose, urinalysis, or thyroid indices. Clinically abnormal ECG.
6. Manic or mixed episode due to a general medical condition or substance-induced mania (DSM-IV-TR).
7. Mental retardation (IQ \<70).
8. History of hypersensitivity to or intolerance of olanzapine or topiramate.
9. Prior history of olanzapine or topiramate non-response or allergic reaction.
10. DSM-IV substance (except nicotine or caffeine) dependence within the past 3 months.
11. Judged clinically to be at suicidal risk (defined as having active suicidal ideation, intent or plan, or a serious suicide attempt within 30 days, or a baseline Children's Depression Rating Scale suicide score of \>3).
12. Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections and day 0.
13. Treatment with concurrent mood stabilizers or anticonvulsants, benzodiazepines (except as described below), psychostimulants, guanethidine, or guanadrel, or antidepressants.
14. Schizophrenia or other psychotic disorders (including schizophreniform disorder, schizoaffective disorder, delusional disorder, brief psychotic disorder, shared psychotic disorder, psychotic disorder due to a general medical condition, substance-induced psychotic disorder, psychotic disorder not otherwise specified) as defined in the DSM-IV.
15. Major depressive disorder, dysthymic disorder, depressive disorder not otherwise specified.

Primary outcomes:
measure: Change in Body Mass Index (BMI)
timeFrame: 12 weeks
measure: Change in Body Weight
timeFrame: 12 weeks
Secondary outcomes:
measure: Tolerability of Topiramate
timeFrame: 12 weeks
Other outcomes:
Locations:
city: Cincinnati
country: United States
facility: University of Cincinnati Medical Center
state: Ohio
Study officials:
affiliation: University of Cincinnati
name: Melissa P DelBello, MD
role: PRINCIPAL_INVESTIGATOR
References: