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

Primary Purpose

Schizophrenia, Schizoaffective Disorders

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
olanzapine
amantadine
metformin
zonisamide
Wellness education
Sponsored by
Eli Lilly and Company
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Schizophrenia

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
  • For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Olanzapine

Olanzapine + Amantadine

Olanzapine + Metformin

Arm Description

olanzapine plus behavioral information

Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information

Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information

Outcomes

Primary Outcome Measures

Change From Baseline to Endpoint in Weight

Secondary Outcome Measures

Mean Change From Baseline to Endpoint in Fasting Triglycerides
Mean Change From Baseline to Endpoint in Fasting Total Cholesterol
Mean Change From Baseline to Endpoint in Fasting High Density Lipoprotein (HDL) Cholesterol
Mean Change From Baseline to Endpoint in Fasting Low Density Lipoprotein (LDL) Cholesterol
Mean Change From Baseline to Endpoint in Fasting Glucose
Mean Change From Baseline to Endpoint in Hemoglobin A1c
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.
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).
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).
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.

Full Information

First Posted
November 17, 2006
Last Updated
September 30, 2009
Sponsor
Eli Lilly and Company
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1. Study Identification

Unique Protocol Identification Number
NCT00401973
Brief Title
Assessment of Safety and Efficacy of Therapy for the Prevention of Weight Gain Associated With Olanzapine
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2009
Overall Recruitment Status
Completed
Study Start Date
November 2006 (undefined)
Primary Completion Date
September 2008 (Actual)
Study Completion Date
September 2008 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Eli Lilly and Company

4. Oversight

5. Study Description

Brief Summary
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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Schizophrenia, Schizoaffective Disorders

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
199 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Olanzapine
Arm Type
Experimental
Arm Description
olanzapine plus behavioral information
Arm Title
Olanzapine + Amantadine
Arm Type
Experimental
Arm Description
Olanzapine and Pharmacological Algorithm 1a - amantadine first plus behavioral information
Arm Title
Olanzapine + Metformin
Arm Type
Experimental
Arm Description
Olanzapine and Pharmacological Algorithm 1b - metformin first plus behavioral information
Intervention Type
Drug
Intervention Name(s)
olanzapine
Other Intervention Name(s)
LY170053, Zyprexa
Intervention Description
5-20 milligrams (mg), oral, daily for 22 weeks.
Intervention Type
Drug
Intervention Name(s)
amantadine
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
metformin
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
zonisamide
Intervention Description
Zonisamide, 100-400mg, oral, daily.
Intervention Type
Behavioral
Intervention Name(s)
Wellness education
Intervention Description
weight management
Primary Outcome Measure Information:
Title
Change From Baseline to Endpoint in Weight
Time Frame
Baseline to endpoint (22 weeks)
Secondary Outcome Measure Information:
Title
Mean Change From Baseline to Endpoint in Fasting Triglycerides
Time Frame
Baseline to endpoint (22 weeks)
Title
Mean Change From Baseline to Endpoint in Fasting Total Cholesterol
Time Frame
Baseline to endpoint (22 weeks)
Title
Mean Change From Baseline to Endpoint in Fasting High Density Lipoprotein (HDL) Cholesterol
Time Frame
Baseline to endpoint (22 weeks)
Title
Mean Change From Baseline to Endpoint in Fasting Low Density Lipoprotein (LDL) Cholesterol
Time Frame
Baseline to endpoint (22 weeks)
Title
Mean Change From Baseline to Endpoint in Fasting Glucose
Time Frame
Baseline to endpoint (22 weeks)
Title
Mean Change From Baseline to Endpoint in Hemoglobin A1c
Time Frame
Baseline to endpoint (22 weeks)
Title
Change From Baseline to Endpoint in Brief Psychiatric Rating Scale (BPRS) Total Score
Description
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.
Time Frame
Baseline to endpoint (22 weeks)
Title
Change From Baseline to Endpoint in Montgomery-Asberg Depression Rating Scale (MADRS) Total Score
Description
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).
Time Frame
Baseline to endpoint (22 weeks)
Title
Change From Baseline to Endpoint in Clinical Global Impression - Severity Scale (CGI-S)
Description
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).
Time Frame
Baseline to endpoint (22 weeks)
Title
Correlations Between Weight Changes and Changes in Eating Inventory (EI) and Food Craving Inventory (FCI) at 2 Weeks and 22 Weeks
Description
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.
Time Frame
Baseline to endpoint (22 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
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)
Organizational Affiliation
Eli Lilly and Company
Official's Role
Study Director
Facility Information:
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
National City
State/Province
California
ZIP/Postal Code
91950
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Canton
State/Province
Ohio
ZIP/Postal Code
44708
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Johnson City
State/Province
Tennessee
ZIP/Postal Code
37614
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38105
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Desoto
State/Province
Texas
ZIP/Postal Code
75115
Country
United States
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Rio De Janeiro
ZIP/Postal Code
21020-130
Country
Brazil
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Salvador
ZIP/Postal Code
40301500
Country
Brazil
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Beer Yaacov
ZIP/Postal Code
70350
Country
Israel
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Seoul
ZIP/Postal Code
143-711
Country
Korea, Republic of
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Mexico City
ZIP/Postal Code
14050
Country
Mexico
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Bayamon
ZIP/Postal Code
00961
Country
Puerto Rico
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Ponce
ZIP/Postal Code
00717
Country
Puerto Rico
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
San Juan
ZIP/Postal Code
00907
Country
Puerto Rico
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
San Juan
Country
Puerto Rico
Facility Name
For additional information regarding investigative sites for this trial, contact 1-877-CTLILLY (1-877-285-4559, 1-317-615-4559) Mon - Fri from 9 AM to 5 PM Eastern Time (UTC/GMT - 5 hours, EST), or speak with your personal physician.
City
Moscow
ZIP/Postal Code
117603
Country
Russian Federation

12. IPD Sharing Statement

Citations:
PubMed Identifier
21672497
Citation
Hoffmann VP, Case M, Jacobson JG. Assessment of treatment algorithms including amantadine, metformin, and zonisamide for the prevention of weight gain with olanzapine: a randomized controlled open-label study. J Clin Psychiatry. 2012 Feb;73(2):216-23. doi: 10.4088/JCP.09m05580. Epub 2011 May 17.
Results Reference
derived
PubMed Identifier
20840778
Citation
Case M, Treuer T, Karagianis J, Hoffmann VP. The potential role of appetite in predicting weight changes during treatment with olanzapine. BMC Psychiatry. 2010 Sep 14;10:72. doi: 10.1186/1471-244X-10-72.
Results Reference
derived

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

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