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A Study of Zonisamide to Prevent Olanzapine-Associated Weight Gain

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ClinicalTrials.gov Identifier: NCT00363376
Recruitment Status : Completed
First Posted : August 15, 2006
Last Update Posted : April 13, 2012
Sponsor:
Collaborators:
Eli Lilly and Company
University of Cincinnati
Information provided by (Responsible Party):
Lindner Center of HOPE

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.

Condition or disease Intervention/treatment Phase
Weight Gain Drug: zonisamide Drug: olanzapine Drug: Zonisamide Drug: Sugar Pill (placebo) Phase 3

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.


Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 42 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Double-Blind, Placebo-Controlled Study of Zonisamide to Prevent Olanzapine-Associated Weight Gain
Study Start Date : January 2008
Actual Primary Completion Date : February 2011
Actual Study Completion Date : February 2011

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Body Weight
U.S. FDA Resources

Arm Intervention/treatment
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



Primary Outcome Measures :
  1. change in weight from baseline to endpoint [ Time Frame: 16 weeks ]

Secondary Outcome Measures :
  1. changes, from baseline to endpoint, in BMI [ Time Frame: 16 weeks ]
  2. changes, from baseline to endpoint, in abdominal circumference [ Time Frame: 16 weeks ]
  3. changes, from baseline to endpoint, in metabolic parameters [ Time Frame: 16 weeks ]
  4. changes, from baseline to endpoint, in clinical global improvement of psychiatric symptoms [ Time Frame: 16 weeks ]
  5. changes, from baseline to endpoint, in manic symptoms [ Time Frame: 16 weeks ]
  6. changes, from baseline to endpoint, in depressive symptoms [ Time Frame: 16 weeks ]
  7. changes, from baseline to endpoint, in psychotic symptoms [ Time Frame: 16 weeks ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): 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

Publications of Results:
Responsible Party: Lindner Center of HOPE
ClinicalTrials.gov Identifier: NCT00363376     History of Changes
Other Study ID Numbers: 06-06-14-01
F1D-MC-X269
First Posted: August 15, 2006    Key Record Dates
Last Update Posted: April 13, 2012
Last Verified: April 2012

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
Olanzapine
Zonisamide
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Psychotropic Drugs
Serotonin Uptake Inhibitors
Neurotransmitter Uptake Inhibitors
Membrane Transport Modulators
Molecular Mechanisms of Pharmacological Action
Neurotransmitter Agents
Serotonin Agents
Anticonvulsants
Antioxidants
Protective Agents