Assessment of Safety and Efficacy of Therapy for the Prevention of Weight Gain Associated With Olanzapine

Study Overview
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Brief Summary
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The goal of this study is to answer the following questions: Whether treatment with amantadine, metformin or zonisamide can prevent or reverse the weight gain that is associated with olanzapine Whether taking amantadine, metformin or zonisamide can help patients decrease or eliminate some of the changes in body that occur with weight gain How weight gain associated with olanzapine can affect people Whether treatment with amantadine, metformin or zonisamide can help eliminate weight gain associated with olanzapine and not interfere with the positive effects of olanzapine on functioning of people with schizophrenia and other diseases

Official Title
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The Assessment of the Safety, Efficacy, and Practicality of an Algorithm Including Amantadine, Metformin and Zonisamide for the Prevention of Olanzapine-Associated Weight Gain in Outpatients With Schizophrenia

Conditions
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Schizophrenia, Schizoaffective Disorders

Intervention / Treatment
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* Drug: olanzapine
* Drug: amantadine
* Drug: metformin
* Drug: zonisamide
* Behavioral: Wellness education


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: You must have been diagnosed with schizophrenia or schizoaffective disorder You must be able to visit the doctor's office once every two weeks for three months, then once every four weeks for the next three months with a possible bi-weekly visit during the fifth month If you are currently taking a medication for schizophrenia or schizoaffective disorder, you have been taking it for at least 30 days without any changes If you are a female, you must have a negative pregnancy test and be using an effective method of contraception Exclusion Criteria: You have a diagnosis of bipolar I disorder, diabetes, very high triglyceride level (fasting triglycerides greater than or equal to 500 mg/dL), recent heart attack, stroke, uncontrolled seizures, serious infection, unstable heart disease (such as ischemic heart disease or congestive heart failure), an uncorrected narrow angle glaucoma or human immunodeficiency virus (HIV) You have diseases of the intestinal tract, lungs, liver, kidney, nervous or endocrine systems, or blood You have a diagnosis of an eating disorder You have a history of Parkinson's Disease or any related disorders You are allergic to sulfa drugs or any of the medications involved in this study

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Olanzapine<br>olanzapine plus behavioral information | Drug: olanzapine<br>* 5-20 milligrams (mg), oral, daily for 22 weeks.<br>* Other names: Zyprexa;Behavioral: Wellness education<br>* weight management<br>|
| Experimental: Olanzapine + Amantadine<br>Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information | Drug: olanzapine<br>* 5-20 milligrams (mg), oral, daily for 22 weeks.<br>* Other names: Zyprexa;Drug: amantadine<br>* Amantadine, 100 milligrams (mg), oral, 1 twice a day (BID). Patients who gained greater than 3 kilograms (kg) will switch to metformin. Patients who gained greater than 3 kg after switching to metformin will be switched to zonisamide.<br>Drug: metformin<br>* Metformin, 500 mg, oral, twice a day (BID) for 2 weeks titrated to 500mg three times a day (TID) thereafter. Patients who gain greater than 3 kilograms (kg) will be switched to amantadine. Patients who gained greater than 3 kg after switching to amantadine will be switched to zonisamide.<br>Drug: zonisamide<br>* Zonisamide, 100-400mg, oral, daily.<br>Behavioral: Wellness education<br>* weight management<br>|
| Experimental: Olanzapine + Metformin<br>Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information | Drug: olanzapine<br>* 5-20 milligrams (mg), oral, daily for 22 weeks.<br>* Other names: Zyprexa;Drug: amantadine<br>* Amantadine, 100 milligrams (mg), oral, 1 twice a day (BID). Patients who gained greater than 3 kilograms (kg) will switch to metformin. Patients who gained greater than 3 kg after switching to metformin will be switched to zonisamide.<br>Drug: metformin<br>* Metformin, 500 mg, oral, twice a day (BID) for 2 weeks titrated to 500mg three times a day (TID) thereafter. Patients who gain greater than 3 kilograms (kg) will be switched to amantadine. Patients who gained greater than 3 kg after switching to amantadine will be switched to zonisamide.<br>Drug: zonisamide<br>* Zonisamide, 100-400mg, oral, daily.<br>Behavioral: Wellness education<br>* weight management<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Endpoint in Weight |  | Baseline to endpoint (22 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Change From Baseline to Endpoint in Fasting Triglycerides |  | Baseline to endpoint (22 weeks) | 
| Mean Change From Baseline to Endpoint in Fasting Total Cholesterol |  | Baseline to endpoint (22 weeks) | 
| Mean Change From Baseline to Endpoint in Fasting High Density Lipoprotein (HDL) Cholesterol |  | Baseline to endpoint (22 weeks) | 
| Mean Change From Baseline to Endpoint in Fasting Low Density Lipoprotein (LDL) Cholesterol |  | Baseline to endpoint (22 weeks) | 
| Mean Change From Baseline to Endpoint in Fasting Glucose |  | Baseline to endpoint (22 weeks) | 
| Mean Change From Baseline to Endpoint in Hemoglobin A1c |  | Baseline to endpoint (22 weeks) | 
| Change From Baseline to Endpoint in Brief Psychiatric Rating Scale (BPRS) Total Score | The BPRS is an 18-item clinician-administered scale used to assess the degree of severity of a subject's general psychopathological symptoms. Each item is rated on a scale from 1 (symptom not present) to 7 (symptom extremely severe). The BPRS total score ranges from 18 to 126. | Baseline to endpoint (22 weeks) | 
| Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score | The MADRS is a rating scale for severity of depressive mood symptoms. The MADRS has a 10-item checklist. Items are rated on a scale of 0-6, for a total score range of 0 (low severity of depressive symptoms) to 60 (high severity of depressive symptoms). | Baseline to endpoint (22 weeks) | 
| Change From Baseline to Endpoint in Clinical Global Impression - Severity Scale (CGI-S) | Measures severity of illness at the time of assessment compared with start of treatment. Scores range from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). | Baseline to endpoint (22 weeks) | 
| Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks | To understand the drivers of weight gain as indicated by the correlation between weight changes and changes in the Eating Inventory (EI) and Food Craving Inventory (FCI). The EI is a 51-item inventory that measures dietary restraint, disinhibition, and perceived hunger. The FCI is a 28-item instrument measuring the frequency over the past month of general cravings and cravings for specific types of foods, namely: high fats, sweets, carbohydrates/starches, and fast-food fats. Correlations were computed on the combined treatment groups. | Baseline to endpoint (22 weeks) |