Official Title: “A Double-Blind, Placebo-Controlled Study of Zonisamide to Prevent Olanzapine-Associated Weight Gain”

The specific aim of this study is to evaluate the efficacy, tolerability, and safety of zonisamide therapy in the prevention of weight gain associated with olanzapine treatment for psychotic or bipolar disorders.

Study Type: Interventional

Study Design: Prevention, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: June 2009

This is a single center, 16-week, randomized, double-blind, placebo-controlled, parallel group, flexible-dose study in 60 outpatients with schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, psychotic disorder NOS, or bipolar disorder types I, II, or NOS by DSM-IV-TR criteria43 with a BMI > 22 for whom treatment with olanzapine (5-20 mg/day) would be appropriate as monotherapy or adjunctive therapy. Subjects who meet entry criteria will be randomized to treatment with olanzapine plus zonisamide or olanzapine plus placebo. All subjects will receive Personal Wellness Solution Counseling (http://www.zyprexa.com/hcp/hcp_patient_c_solutions_print.jsp). Both before and after randomization to zonisamide or placebo, patients will not be permitted to have any other major psychotropic medications (antipsychotics, mood stabilizers, antidepressants, or anxiolytics) added to their medication regimens. The primary outcome measure will be change in weight. Secondary outcome measures will include the Young Mania Rating Scale (YMRS),44 the Inventory for Depressive Symptoms (IDS),45 the Positive and Negative Symptoms Scale (PANSS),46 the Clinician Global Improvement (CGI) scale,47 the Binge Eating Scale (BES) 48, BMI, waist circumference, and metabolic variables (fasting lipids, glucose, insulin).

Subjects will be inpatients or outpatients at the time of randomization to olanzapine-zonisamide or olanzapine-placebo. Throughout the study, psychiatric scales will be used to assess psychiatric symptoms, and the presence of treatment-emergent adverse events will be monitored and recorded.

Intervention(s) in this Clinical Trial

• Drug: zonisamide
  • Zonisamide will be administered at an initial dose of 100 mg/d for 7 days. Subsequently, zonisamide may be increased, based on clinical response and tolerability, by 100mg/d every 7 days to a maximum of 600 mg/d by the end of the sixth week of treatment. The maximum amount of zonisamide allowed during the study will be 600 mg/day. The minimum amount of zonisamide allowed during the study will be 100 mg/d. Zonisamide will initially be given as a single pm dose, but alterations in dosing will be permitted to reduce side effects (e.g., as BID dosing to reduce nausea).
• Drug: olanzapine
  • olanzapine will be administered open-label at 5-20 mg/d titrated to optimize response and minimize side effects

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • olanzapine & zonisamide vs olanzapine & placebo

Primary Measures

• change in weight from baseline to endpoint
  • Time Frame: 16 weeks
    Safety Issue?: No

Secondary Measures

• changes, from baseline to endpoint, in BMI
  • Time Frame: 16 weeks
    Safety Issue?: No
• changes, from baseline to endpoint, in abdominal circumference
  • Time Frame: 16 weeks
    Safety Issue?: No
• changes, from baseline to endpoint, in metabolic parameters
  • Time Frame: 16 weeks
    Safety Issue?: Yes
• changes, from baseline to endpoint, in clinical global improvement of psychiatric symptoms
  • Time Frame: 16 weeks
    Safety Issue?: Yes
• changes, from baseline to endpoint, in manic symptoms
  • Time Frame: 16 weeks
    Safety Issue?: Yes
• changes, from baseline to endpoint, in depressive symptoms
  • Time Frame: 16 weeks
    Safety Issue?: Yes
• changes, from baseline to endpoint, in psychotic symptoms
  • Time Frame: 16 weeks
    Safety Issue?: Yes

Inclusion Criteria:

Criteria for entering this study will include all of the following:

• 1. Subjects must be 18 years of age or older.
• 2. Subjects must have schizophrenia, schizoaffective disorder, schizophreniform disorder, delusional disorder, psychotic disorder NOS, or bipolar I, II, or NOS disorder as defined by DSM-IV-TR criteria.
• 3. Subjects must have a BMI > 22.
• 4. Subjects must sign the Informed Consent Document after the nature of the trial has been fully explained.
• 5. If female, subjects must be: postmenopausal, surgically incapable of childbearing, or practicing medically acceptable effective method(s) of contraception (e.g., hormonal methods, intrauterine device) for at least one month prior to study entry and throughout the study.
• 6. If exposed to olanzapine in the past, subjects must be free of olanzapine for > 3 months prior to randomization to study medication.

Exclusion Criteria:

Criteria for exclusion from this study will be any of the following:

• 1. Subjects with clinically significant suicidal or homicidal ideation.
• 2. Subjects with a current DSM-IV Axis I diagnosis of delirium, dementia, amnesia, or other cognitive disorders; a psychotic or mood disorder secondary to substance use or a general medical disorder; or a DSM-IV diagnosis of a substance use disorder within the past six months.
• 3. Cardiovascular, endocrine, neurologic, or hematologic disease as determined by the clinical judgment of the clinical investigator. Subjects with hypo- or hyperthyroidism unless stabilized on thyroid replacement > 3 months.
• 4. Subjects who are allergic to or who have demonstrated hypersensitivity to or significant adverse event from olanzapine.
• 5. Subjects who are allergic to or who have demonstrated hypersensitivity to zonisamide.
• 6. Women who are pregnant or nursing.
• 7. Subjects who have received an experimental drug or used an experimental device within 30 days.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: University of Cincinnati

Overall Clinical Trial Officials and Contacts

Susan McElroy, MD Principal Investigator University of Cincinnati  

Overall Contact: Susan McElroy, MD (513) 558-1132 susan.mcelroy@uc.edu

Information obtained from ClinicalTrials.gov on October 10, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00363376

Study ID Number: 06-06-14-01

ClinicalTrials.gov Identifier: NCT00363376

Health Authority: United States: Institutional Review Board