Topiramate vs. Placebo in Preventing Weight Gain in Bipolar Disorder Treated With Olanzapine

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

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.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder; Weight Gain
• Intervention / Treatment: Drug: Topiramate; Drug: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 31
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45267-0559
      • University of Cincinnati Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 10 years to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Topiramate Group; Patients' initial dose of topiramate 25mg bid, which was titrated over 18 days to 150 mg bid (with flexibility to titrate to 200mg bid) as tolerated.	Drug: Topiramate; Oral topiramate 300-400mg/day for 12 weeks; Other Names: Topamax
Placebo Comparator: Placebo Group; Sugar pill	Drug: Placebo; Matched placebo to Experimental arm; Other Names: Sugar pill

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Body Mass Index (BMI)	For all participants, BMI was computed using Change in BMI [kg/m2 (weight/height2)] over 12 weeks from Baseline to Week 12.	12 weeks
Change in Body Weight	For all participants, change in body weight in kg over 12 weeks from Baseline to Week 12.	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tolerability of Topiramate	To examine the tolerability of topiramate in combination with olanzapine for the prevention of weight gain in youth with bipolar disorder.	12 weeks

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Collaborators: Eli Lilly and Company
• Investigators: Principal Investigator: Melissa P DelBello, MD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start: December 1, 2006
• Primary Completion (Actual): August 1, 2009
• Study Completion (Actual): September 1, 2009

Study Registration Dates

• First Submitted: October 27, 2006
• First Submitted That Met QC Criteria: October 27, 2006
• First Posted (Estimate): October 31, 2006

Study Record Updates

• Last Update Posted (Estimate): April 4, 2013
• Last Update Submitted That Met QC Criteria: April 3, 2013
• Last Verified: April 1, 2013

More Information

Terms related to this study

• Keywords: Bipolar Disorder; Weight Gain
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Body Weight Changes; Bipolar and Related Disorders; Disease; Bipolar Disorder; Body Weight; Weight Gain; Hypoglycemic Agents; Physiological Effects of Drugs; Anticonvulsants; Topiramate
• Other Study ID Numbers: F1D-MC-X304