A Study of Zonisamide to Prevent Olanzapine-Associated Weight Gain - Full Text View

Sponsor:	Lindner Center of HOPE
Collaborators:	Eli Lilly and Company University of Cincinnati
Information provided by:	Lindner Center of HOPE
ClinicalTrials.gov Identifier:	NCT00363376

Purpose

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.

Condition	Intervention	Phase
Weight Gain	Drug: zonisamide Drug: olanzapine Drug: Zonisamide Drug: Sugar Pill (placebo)	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Parallel Assignment Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor) Primary Purpose: Prevention
Official Title:	A Double-Blind, Placebo-Controlled Study of Zonisamide to Prevent Olanzapine-Associated Weight Gain

Resource links provided by NLM:

MedlinePlus related topics: Bipolar Disorder Mental Disorders Psychotic Disorders

Drug Information available for: Zonisamide Olanzapine

U.S. FDA Resources

Further study details as provided by Lindner Center of HOPE:

Primary Outcome Measures:

change in weight from baseline to endpoint [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

changes, from baseline to endpoint, in BMI [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
changes, from baseline to endpoint, in abdominal circumference [ Time Frame: 16 weeks ] [ Designated as safety issue: No ]
changes, from baseline to endpoint, in metabolic parameters [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
changes, from baseline to endpoint, in clinical global improvement of psychiatric symptoms [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
changes, from baseline to endpoint, in manic symptoms [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
changes, from baseline to endpoint, in depressive symptoms [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]
changes, from baseline to endpoint, in psychotic symptoms [ Time Frame: 16 weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	40
Study Start Date:	January 2008
Study Completion Date:	February 2011
Primary Completion Date:	February 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: Sugar pill olanzapine and placebo ("sugar pill")	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). Other Name: Zonegran Drug: olanzapine olanzapine will be administered open-label at 5-20 mg/d titrated to optimize response and minimize side effects Other Names: Zyprexa Zydis Drug: Sugar Pill (placebo) sugar pill (placebo) for zonisamide
Experimental: Zonisamide olanzapine and zonisamide (active drug)	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). Other Name: Zonegran Drug: olanzapine olanzapine will be administered open-label at 5-20 mg/d titrated to optimize response and minimize side effects Other Names: Zyprexa Zydis Drug: Zonisamide zonisamide ranging from 100mg to 600mg daily Other Name: Zonegran

Arms

Assigned Interventions

Experimental: Sugar pill

olanzapine and placebo ("sugar pill")

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).

Other Name: Zonegran

Drug: olanzapine

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

Other Names:

Zyprexa
Zydis

Drug: Sugar Pill (placebo)

sugar pill (placebo) for zonisamide

Experimental: Zonisamide

olanzapine and zonisamide (active drug)

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).

Other Name: Zonegran

Drug: olanzapine

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

Other Names:

Zyprexa
Zydis

Drug: Zonisamide

zonisamide ranging from 100mg to 600mg daily

Other Name: Zonegran

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.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

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

Subjects must be 18 years of age or older.
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.
Subjects must have a BMI > 22.
Subjects must sign the Informed Consent Document after the nature of the trial has been fully explained.
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.
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:

Subjects with clinically significant suicidal or homicidal ideation.
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.
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.
Subjects who are allergic to or who have demonstrated hypersensitivity to or significant adverse event from olanzapine.
Subjects who are allergic to or who have demonstrated hypersensitivity to zonisamide.
Women who are pregnant or nursing.
Subjects who have received an experimental drug or used an experimental device within 30 days.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00363376

Locations

United States, Ohio
The Lindner Center of HOPE
Mason, Ohio, United States, 45040

Sponsors and Collaborators

Lindner Center of HOPE

Eli Lilly and Company

University of Cincinnati

Investigators

Principal Investigator:

Susan McElroy, MD

The Lindner Center of HOPE

More Information

No publications provided

Responsible Party:	Susan McElroy, MD, The Lindner Center of HOPE
ClinicalTrials.gov Identifier:	NCT00363376 History of Changes
Other Study ID Numbers:	06-06-14-01, F1D-MC-X269
Study First Received:	August 9, 2006
Last Updated:	June 21, 2011
Health Authority:	United States: Institutional Review Board; United States: Food and Drug Administration

Keywords provided by Lindner Center of HOPE:

olanzapine
zonisamide
weight gain
bipolar disorder
psychotic disorders

Additional relevant MeSH terms:

Body Weight
Weight Gain
Signs and Symptoms
Body Weight Changes
Zonisamide
Olanzapine
Antioxidants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protective Agents
Physiological Effects of Drugs
Anticonvulsants
Central Nervous System Agents

Therapeutic Uses
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Neurotransmitter Agents
Serotonin Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents

ClinicalTrials.gov processed this record on February 09, 2012