Back to resultsShort Term Rescue Study of Olanzapine
Primary Purpose
Bipolar Disorder
Status
Completed
Phase
Phase 4
Locations
United States
Study Type
Interventional
Intervention
Olanzapine/Zyprexa
Sponsored by
About this trial
This is an interventional treatment trial for Bipolar Disorder
Eligibility Criteria
Inclusion Criteria:Patients must meet the following criteria to be eligible to participate in the study: Male or female outpatients, 18 to 70 years of age Female patients of childbearing potential must be using a medically accepted means of contraception Able to communicate intelligently with the investigator, and study coordinator Able to give informed consent DSM-IV diagnosis of bipolar I, bipolar II, cyclothymic disorder or bipolar disorder not otherwise specified, experiencing an acute exacerbation of their illness at Visit 1 (hypomania, subsyndromal depression, hypomania and subsyndromal depression, depression and hypomania, or depression if diagnosed with bipolar II) as verified by SCID-I/P CGI-BP Overall Severity score greater than or equal to mildly ill at Visit 1 Must have been on prior medications for at least 2 weeks (6 weeks for fluoxetine) immediately prior to study entry Exclusion Criteria:Patients may not participate in the study if they have any of the following conditions: Pregnant, nursing, or intending to become pregnant during the study Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease such that hospitalization for the disease is anticipated within 3 months or death is anticipated within 3 years. A history of seizure disorder History of leukopenia without a clear and resolved etiology. DSM-IV substance (except nicotine or caffeine) dependence within the past month Judged clinically to be at serious suicidal risk Participation in clinical trial of another investigational drug within 1 month (30 days) prior to study entry. Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections prior to study entry Treatment resistance, non-response, or intolerability with olanzapine by the investigator's judgment Treatment with clozapine within 3 months prior to study entry Treatment with remoxipride within 6 months (180 days) prior to study entry Treatment with an oral antipsychotic within 2 days prior to study entry A course of ECT (electroconvulsive therapy) in the preceding 4 weeks Excluded mood symptoms noted in Table 1 [of protocol] Unstable thyroid pathology and treatment-initiated or altered within the past 3 months Meet criteria for antisocial personality disorder
Sites / Locations
- Stanford University School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Placebo Comparator
Arm Label
Olanzapine/Zyprexa
Placebo
Arm Description
Olanzapine/Zyprexa 2.5 mg up to 8 per day for 1 week
Placebo was taken in the same manner as olanzapine with up to 8 per day for 1 week
Outcomes
Primary Outcome Measures
Mean Change in CGI-BP-OS After 1 Week of Treatment
The Clinical Global Impression - bipolar version - overall severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not ill; 2, minimally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, very severely ill
Secondary Outcome Measures
Mean Change in YMRS After 1 Week of Treatment
The Young Mania Rating Scale (YMRS) scale has 11 items and is based on the patient's subjective report of his or her clinical condition over the previous 48 hours. Responses to each item are summed with a higher score indicating more mania symptoms endorsed.
Scale:0-60 0=Good 60=Bad
Mean Change in MADRS After 1 Week of Treatment.
Montgomery-Asberg Depression Rating Scales (MADRS) is a multi-item clinician tool assessing depression. Each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Higher MADRS score indicates more severe depression.
Mean Change in Hamilton Anxiety Rating Scales (HAM-A)
The HAM-A was one of the first rating scales developed to measure the severity of anxiety symptoms, and is still widely used today in both clinical and research settings. The scale consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). The HAM-A does not provide any standardized probe questions. Despite this,the reported levels of interrater reliability for the scale appear to be acceptable.
Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Full Information
NCT ID
NCT00186017
First Posted
September 12, 2005
Last Updated
April 12, 2017
Sponsor
Stanford University
Collaborators
Eli Lilly and Company
1. Study Identification
Unique Protocol Identification Number
NCT00186017
Brief Title
Short Term Rescue Study of Olanzapine
Official Title
Double-Blind Placebo-Controlled Olanzapine Add-on Therapy in the Treatment of Acute Syndromal and Subsyndromal Exacerbations in Bipolar Disorders
Study Type
Interventional
2. Study Status
Record Verification Date
April 2017
Overall Recruitment Status
Completed
Study Start Date
July 2005 (undefined)
Primary Completion Date
June 2010 (Actual)
Study Completion Date
June 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Stanford University
Collaborators
Eli Lilly and Company
4. Oversight
Data Monitoring Committee
No
5. Study Description
Brief Summary
We will assess the effect of olanzapine compared to placebo added to prior treatment on CGI-S in a one-week randomized double-blind study. We will also assess the effect of olanzapine added to prior treatment on CGI-S in an eight-week open treatment study. In addition, we will assess the effect of olanzapine on Young Mania Rating Scale (YMRS), Hamilton and Montgomery-Asberg Depression Rating Scales (HDRS, and MADRS), and Hamilton Anxiety Rating Scales (HARS) in the above paradigms. We will also assess the influence of presentation severity (CGI-S) and polarity (mood elevation versus depression) on olanzapine response. Finally, we will assess safety and tolerability of olanzapine in the above paradigms.
We hypothesize that in diverse mild syndromal and subsyndromal exacerbations of BD in outpatients, randomized double-blind flexibly dosed olanzapine added to prior treatment (including no treatment) will yield greater CGI-S improvement than placebo by the end of one week, and that such improvement will persist over one week of open continuation treatment.
Detailed Description
Development and marketing of new therapies for bipolar disorders (BD) has typically entailed performing double-blind placebo-controlled trials in acute mania maintenance studies and more recently acute depression studies. Such an approach addresses BD primarily in terms of episodes and has the strength of studying levels of pathology sufficiently high to permit detection of treatment effects, and guiding clinicians when they encounter syndromal mood episodes. However, this approach has the important limitation of not addressing an important unmet clinical need, namely the management of subsyndromal symptoms. Indeed, emerging data suggest that in BD subsyndromal symptoms compared to syndromal episodes are far more pervasive. Also such an approach runs the risk of not paying sufficient attention to the disorder construct, in a sense permitting preoccupation with syndromal episodes to carry more importance than the disorder.
We will assess the effect of olanzapine compared to placebo added to prior treatment on CGI-S in a one-week randomized double-blind study. We will also assess the effect of olanzapine added to prior treatment on CGI-S in an eight-week open treatment study. In addition, we will assess the effect of olanzapine on Young Mania Rating Scale (YMRS), Hamilton and Montgomery-Asberg Depression Rating Scales (HDRS, and MADRS), and Hamilton Anxiety Rating Scales (HARS) in the above paradigms. We will also assess the influence of presentation severity (CGI-S) and polarity (mood elevation versus depression) on olanzapine response. Finally, we will assess safety and tolerability of olanzapine in the above paradigms.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Bipolar Disorder
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Olanzapine/Zyprexa
Arm Type
Experimental
Arm Description
Olanzapine/Zyprexa 2.5 mg up to 8 per day for 1 week
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo was taken in the same manner as olanzapine with up to 8 per day for 1 week
Intervention Type
Drug
Intervention Name(s)
Olanzapine/Zyprexa
Other Intervention Name(s)
Zyprexa
Intervention Description
Olanzapine was started at 2.5-10mg/day and adjusted by 2.5-5mg/day on a daily basis with a maximum dose of 20mg/day.
Primary Outcome Measure Information:
Title
Mean Change in CGI-BP-OS After 1 Week of Treatment
Description
The Clinical Global Impression - bipolar version - overall severity scale (CGI-S) is a 7-point scale that requires the clinician to rate the severity of the patient's illness at the time of assessment, relative to the clinician's past experience with patients who have the same diagnosis. Considering total clinical experience, a patient is assessed on severity of mental illness at the time of rating 1, normal, not ill; 2, minimally ill; 3, mildly ill; 4, moderately ill; 5, markedly ill; 6, severely ill; or 7, very severely ill
Time Frame
Baseline, 1 Week
Secondary Outcome Measure Information:
Title
Mean Change in YMRS After 1 Week of Treatment
Description
The Young Mania Rating Scale (YMRS) scale has 11 items and is based on the patient's subjective report of his or her clinical condition over the previous 48 hours. Responses to each item are summed with a higher score indicating more mania symptoms endorsed.
Scale:0-60 0=Good 60=Bad
Time Frame
Baseline, 1 week
Title
Mean Change in MADRS After 1 Week of Treatment.
Description
Montgomery-Asberg Depression Rating Scales (MADRS) is a multi-item clinician tool assessing depression. Each item yields a score of 0 to 6. The overall score ranges from 0 to 60. Higher MADRS score indicates more severe depression.
Time Frame
Baseline, 1 week
Title
Mean Change in Hamilton Anxiety Rating Scales (HAM-A)
Description
The HAM-A was one of the first rating scales developed to measure the severity of anxiety symptoms, and is still widely used today in both clinical and research settings. The scale consists of 14 items, each defined by a series of symptoms, and measures both psychic anxiety (mental agitation and psychological distress) and somatic anxiety (physical complaints related to anxiety). The HAM-A does not provide any standardized probe questions. Despite this,the reported levels of interrater reliability for the scale appear to be acceptable.
Each item is scored on a scale of 0 (not present) to 4 (severe), with a total score range of 0-56, where <17 indicates mild severity, 18-24 mild to moderate severity and 25-30 moderate to severe.
Time Frame
Baseline, 1 Week
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
70 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:Patients must meet the following criteria to be eligible to participate in the study:
Male or female outpatients, 18 to 70 years of age
Female patients of childbearing potential must be using a medically accepted means of contraception
Able to communicate intelligently with the investigator, and study coordinator
Able to give informed consent
DSM-IV diagnosis of bipolar I, bipolar II, cyclothymic disorder or bipolar disorder not otherwise specified, experiencing an acute exacerbation of their illness at Visit 1 (hypomania, subsyndromal depression, hypomania and subsyndromal depression, depression and hypomania, or depression if diagnosed with bipolar II) as verified by SCID-I/P
CGI-BP Overall Severity score greater than or equal to mildly ill at Visit 1
Must have been on prior medications for at least 2 weeks (6 weeks for fluoxetine) immediately prior to study entry Exclusion Criteria:Patients may not participate in the study if they have any of the following conditions:
Pregnant, nursing, or intending to become pregnant during the study
Serious, unstable illnesses including hepatic, renal, gastroenterologic, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease such that hospitalization for the disease is anticipated within 3 months or death is anticipated within 3 years.
A history of seizure disorder
History of leukopenia without a clear and resolved etiology.
DSM-IV substance (except nicotine or caffeine) dependence within the past month
Judged clinically to be at serious suicidal risk
Participation in clinical trial of another investigational drug within 1 month (30 days) prior to study entry.
Treatment with an injectable depot neuroleptic within less than one dosing interval between depot neuroleptic injections prior to study entry
Treatment resistance, non-response, or intolerability with olanzapine by the investigator's judgment
Treatment with clozapine within 3 months prior to study entry
Treatment with remoxipride within 6 months (180 days) prior to study entry
Treatment with an oral antipsychotic within 2 days prior to study entry
A course of ECT (electroconvulsive therapy) in the preceding 4 weeks
Excluded mood symptoms noted in Table 1 [of protocol]
Unstable thyroid pathology and treatment-initiated or altered within the past 3 months
Meet criteria for antisocial personality disorder
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Terence Arthur Ketter
Organizational Affiliation
Stanford University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Stanford University School of Medicine
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Links:
URL
http://bipolar.org
Description
Stanford University Bipolar Disorders Clinic
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Short Term Rescue Study of Olanzapine
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