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

Bipolar Disorder Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00394095
• Other study ID #: F1D-MC-X304
• Status: Completed
• Phase: Phase 4
• First received: October 27, 2006
• Last updated: April 3, 2013
• Start date: December 2006
• Est. completion date: September 2009

Study information

• Verified date: April 2013
• Source: University of Cincinnati
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 31
• Est. completion date: September 2009
• Est. primary completion date: August 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 10 Years to 18 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bipolar Disorder
• Body Weight
• Weight Gain

Intervention

Drug:
• Topiramate
Oral topiramate 300-400mg/day for 12 weeks
• Placebo
Matched placebo to Experimental arm

Locations

Country	Name	City	State
United States	University of Cincinnati Medical Center	Cincinnati	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
University of Cincinnati	Eli Lilly and Company

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Primary	Change in Body Weight	For all participants, change in body weight in kg over 12 weeks from Baseline to Week 12.	12 weeks	No
Secondary	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	Yes