Clinical trial NCT00363376: A Study of Zonisamide to Prevent Olanzapine-Associated Weight Gain
Official title: A Double-Blind, Placebo-Controlled Study of Zonisamide to Prevent Olanzapine-Associated Weight Gain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Weight Gain
Keywords: olanzapine
zonisamide
weight gain
bipolar disorder
psychotic disorders
Lead sponsor: Lindner Center of HOPE
Sponsor class: OTHER
Collaborators: name: Eli Lilly and Company
name: University of Cincinnati
First posted: 2006-08-15
Enrollment: 42
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: change in weight from baseline to endpoint
timeFrame: 16 weeks
Secondary outcomes:
measure: changes, from baseline to endpoint, in BMI
timeFrame: 16 weeks
measure: changes, from baseline to endpoint, in abdominal circumference
timeFrame: 16 weeks
measure: changes, from baseline to endpoint, in metabolic parameters
timeFrame: 16 weeks
measure: changes, from baseline to endpoint, in clinical global improvement of psychiatric symptoms
timeFrame: 16 weeks
measure: changes, from baseline to endpoint, in manic symptoms
timeFrame: 16 weeks
measure: changes, from baseline to endpoint, in depressive symptoms
timeFrame: 16 weeks
measure: changes, from baseline to endpoint, in psychotic symptoms
timeFrame: 16 weeks
Other outcomes:
Locations:
city: Mason
country: United States
facility: The Lindner Center of HOPE
state: Ohio
Study officials:
affiliation: The Lindner Center of HOPE
name: Susan McElroy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.