Official Title: “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”

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

Study Type: Interventional

Study Design: Prevention, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study

Study Primary Completion Date: September 2008

Intervention(s) in this Clinical Trial

• Drug: olanzapine
  • 5-20mg, oral, daily for 22 weeks.
• Drug: amantadine
  • Amantadine, 100mg, oral, 1 BID. Patients who gained greater than 3 Kg will switch to metformin. Patients who gained greater than 3 Kg after switching to metformin will be switched to zonisamide.
• Drug: metformin
  • Metformin, 500mg, oral, BID for 2 weeks titrated to 500mg TID thereafter. Patients who gain greater than 3kg will be switched to amantadine. Patients who gained greater than 3 Kg after switching to amantadine will be switched to zonisamide.
• Drug: zonisamide
  • Zonisamide, 100-400mg, oral, daily.
• Behavioral: Wellness education
  • weight management

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: 1
  • olanzapine plus behavioral information
• Experimental: 2
  • Pharmacological Algorithm 1a - amantadine first plus behavioral information
• Experimental: 3
  • Pharmacological Algorithm 1b - metformin first plus behavioral information

Primary Measures

• Assess whether weight gain associated with olanzapine therapy can be prevented or mitigated with adjunctive therapy by measuring the mean weight change between groups.
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: Yes

Secondary Measures

• Assess differences between groups in terms of mean change in triglycerides.
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: Yes
• Assess differences between groups in terms of mean change in total cholesterol.
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: Yes
• Assess differences between groups in terms of changes in LDL cholesterol.
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: Yes
• Assess changes between groups in terms of changes in fasting glucose.
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: Yes
• Assess changes between groups in terms of mean change in Hemoglobin A1c.
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: Yes
• Assess the difference in psychiatric symptoms between groups in terms of the Brief Psychiatric Rating scale (BPRS).
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: No
• Assess the difference in psychiatric symptoms between groups as measured by the Montgomery-Asberg Depression Rating Scale (MADRS).
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: No
• Assess the difference in psychiatric symptoms between groups as measured by the Clinical Global Impression - Severity scale (CGI-S).
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: No
• To understand the drivers of weight gain as indicated by the correlation between weight changes and changes in the Eating Inventory and Food Craving Inventory.
  • Time Frame: Baseline to endpoint (22 weeks)
    Safety Issue?: No

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 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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 18 Years

Maximum Age for this Clinical Trial: 65 Years

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Eli Lilly and Company

Overall Clinical Trial Officials and Contacts

Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST) Study Director Eli Lilly and Company  

Information obtained from ClinicalTrials.gov on July 02, 2009

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00401973

Study ID Number: 10768

ClinicalTrials.gov Identifier: NCT00401973

Health Authority: United States: Food and Drug Administration

Lilly Clinical Trial Registry