A Study of Zonisamide to Prevent Olanzapine-Associated Weight Gain

NCT ID: NCT00363376

Last Updated: 2012-04-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 42 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-01-31
• Study Completion Date: 2011-02-28

Brief Summary

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.

Detailed Description

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.

Conditions

Weight Gain

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Sugar pill

olanzapine and placebo ("sugar pill")

Group Type: EXPERIMENTAL

zonisamide

Intervention Type: DRUG

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).

olanzapine

Intervention Type: DRUG

olanzapine will be administered open-label at 5-20 mg/d titrated to optimize response and minimize side effects

Sugar Pill (placebo)

Intervention Type: DRUG

sugar pill (placebo) for zonisamide

Zonisamide

olanzapine and zonisamide (active drug)

Group Type: EXPERIMENTAL

zonisamide

Intervention Type: DRUG

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).

olanzapine

Intervention Type: DRUG

olanzapine will be administered open-label at 5-20 mg/d titrated to optimize response and minimize side effects

Zonisamide

Intervention Type: DRUG

zonisamide ranging from 100mg to 600mg daily

Interventions

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).

Intervention Type: DRUG

olanzapine

olanzapine will be administered open-label at 5-20 mg/d titrated to optimize response and minimize side effects

Intervention Type: DRUG

Zonisamide

zonisamide ranging from 100mg to 600mg daily

Intervention Type: DRUG

Sugar Pill (placebo)

sugar pill (placebo) for zonisamide

Intervention Type: DRUG

Other Intervention Names

Zonegran; Zyprexa; Zydis; Zonegran

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Eli Lilly and Company

INDUSTRY

Sponsor Role: collaborator

University of Cincinnati

OTHER

Sponsor Role: collaborator

Lindner Center of HOPE

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Susan McElroy, MD

Role: PRINCIPAL_INVESTIGATOR

The Lindner Center of HOPE

Locations

The Lindner Center of HOPE

Mason, Ohio, United States

Countries

United States

References

McElroy SL, Winstanley E, Mori N, Martens B, McCoy J, Moeller D, Guerdjikova AI, Keck PE Jr. A randomized, placebo-controlled study of zonisamide to prevent olanzapine-associated weight gain. J Clin Psychopharmacol. 2012 Apr;32(2):165-72. doi: 10.1097/JCP.0b013e3182488758.

Reference Type: RESULT

PMID: 22367654 (View on PubMed)

Other Identifiers

F1D-MC-X269

Identifier Type: -

Identifier Source: secondary_id

06-06-14-01

Identifier Type: -

Identifier Source: org_study_id