Bipolar DisorderPhase 4NCT00186017

Short Term Rescue Study of Olanzapine

A Phase 4 study testing Olanzapine/Zyprexa in people with Bipolar Disorder, run by Stanford University at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Who is it for?: Ages 18 to 70 years
Conditions the study is for: Bipolar Disorder
What is being tested?: Olanzapine/Zyprexa
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 50 participants
Where: 1 siteUnited States
Study dates: Jul 2005to Jun 2010
Phase: Phase 4
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 70 years
All sexes
No healthy volunteers
Adult, Older adult

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

Trial locations and contacts

1 site in 1 country.

United States1 site

Stanford University School of Medicine
Stanford, California, 94305

Other trials in United States

About this study

Official title: Double-Blind Placebo-Controlled Olanzapine Add-on Therapy in the Treatment of Acute Syndromal and Subsyndromal Exacerbations in Bipolar Disorders

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.

Read the 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.

Conditions: Bipolar Disorder
Being tested: Olanzapine/Zyprexa
Medical subject headings: Bipolar Disorder

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Olanzapine/ZyprexaDrug
Also called Zyprexa
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.

Study groups in NCT00186017
Study group	Role	What they receive
Olanzapine/Zyprexa	Experimental	Olanzapine/Zyprexa 2.5 mg up to 8 per day for 1 week Receives: Drug: Olanzapine/Zyprexa
Placebo	Placebo comparator	Placebo was taken in the same manner as olanzapine with up to 8 per day for 1 week Receives: Drug: Olanzapine/Zyprexa

What is being measured

The primary outcome is the main question the study is designed to answer.

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
Measured: Baseline, 1 Week

Secondary outcomes (3)

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
Measured: Baseline, 1 week
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.
Measured: Baseline, 1 week
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.
Measured: Baseline, 1 Week

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Jul 2005Jun 2010

First posted16 Sep 2005 (estimated)
Study startJul 2005
Primary completionJun 2010
Study completionJun 2010

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for Bipolar DisorderStudies of the same condition, open and under way.
More trials run by Stanford UniversityThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 50 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00186017
Sponsor's protocol ID: 79897
Other IDs: F1D-US-X279
Status last verified: Apr 2017
First submitted: 12 Sep 2005
Last updated: 16 May 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
Individual data sharing: No

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Recruiting
Safety and Feasibility of DBS for Bipolar Depression
Bipolar I Disorder, Bipolar Depression
Not yet recruiting
Compulsive Eating and Brain's Reward System in Different Pathologies
PARKINSON DISEASE (Disorder), Bipolar 1 Disorder
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Recruiting
Affective Cognitive Training in Mood Disorders and High-risk Relatives
Major Depressive Disorder (MDD), Bipolar Disorder (BD)

All Bipolar Disorder trials

Study at a glance

From the registry record, last updated by the sponsor on 16 May 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Double-Blind Placebo-Controlled Olanzapine Add-on Therapy in the Treatment of Acute Syndromal and Subsyndromal Exacerbations in Bipolar Disorders
ClinicalTrials.gov ID: NCT00186017
Acronym / sponsor ID: 79897
Conditions: Bipolar Disorder
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 50 participants (actual)
Lead sponsor: Stanford UniversityUniversity, hospital or other
Collaborators: Eli Lilly and Company
Study start: Jul 2005
Primary completion: Jun 2010 (actual)
Study completion: Jun 2010 (actual)
First posted: 16 Sep 2005 (estimated)
Results: Posted 16 May 2017

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 2

Arm	Type	Receives
Olanzapine/Zyprexa	Experimental	Drug: Olanzapine/ZyprexaOlanzapine/Zyprexa 2.5 mg up to 8 per day for 1 week
Placebo	Placebo comparator	Drug: Olanzapine/ZyprexaPlacebo was taken in the same manner as olanzapine with up to 8 per day for 1 week

Who may qualify

Ages: 18 to 70 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Olanzapine/ZyprexaAlso: ZyprexaOlanzapine 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.	Drug	Olanzapine/Zyprexa, Placebo

Primary outcome

Mean Change in CGI-BP-OS After 1 Week of Treatment
Time frame: Baseline, 1 Week
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

3 secondary outcomes

Mean Change in YMRS After 1 Week of Treatment
Time frame: Baseline, 1 week
Mean Change in MADRS After 1 Week of Treatment.
Time frame: Baseline, 1 week
Mean Change in Hamilton Anxiety Rating Scales (HAM-A)
Time frame: Baseline, 1 Week

Results and safety

Results posted to the registry on 16 May 2017, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Olanzapine/Zyprexa	25	23
Placebo	25	22

Primary outcome: Mean Change in CGI-BP-OS After 1 Week of Treatment

Time frame: Baseline, 1 Week. Mean (Standard Deviation). Unit: units on a scale

Measure	Olanzapine/Zyprexa n = 23	Placebo n = 22
Value	-1.4 (0.9)	.8 (1.1)

Olanzapine/Zyprexa vs Placebo: p = .08, Wilcoxon (Mann-Whitney)

3 secondary outcomes are reported in the full results.

Adverse events

Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Olanzapine/Zyprexa	0 of 23 (0%)	22 of 23 (95.7%)	Not reported
Placebo	0 of 22 (0%)	20 of 22 (90.9%)	Not reported

Limitations and caveats (from the sponsor): Small Sample Size.

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 16 May 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Stanford University Bipolar Disorders ClinicLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Bipolar Disorder

Not yet recruitingObservational study
Sleep Monitoring for Early Detection of Relapse in People With Schizophrenia or Bipolar Disorder Receiving Usual Treatment
Bipolar Disorder (BD), SCHIZOPHRENIA 1 (Disorder)
Recruiting
Safety and Feasibility of DBS for Bipolar Depression
Bipolar I Disorder, Bipolar Depression
Not yet recruiting
Compulsive Eating and Brain's Reward System in Different Pathologies
PARKINSON DISEASE (Disorder), Bipolar 1 Disorder
Not yet recruitingPhase 1
Pharmacokinetics and Relative Bioavailability of Intranasal vs Intramuscular Olanzapine in Healthy Adult Participants
Healthy Adult Participants
Recruiting
Affective Cognitive Training in Mood Disorders and High-risk Relatives
Major Depressive Disorder (MDD), Bipolar Disorder (BD)

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Terence Arthur Ketter principal investigator

Stanford University

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Olanzapine/Zyprexa in people with Bipolar Disorder, run by Stanford University at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 May 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 16 May 2017). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mean Change in CGI-BP-OS After 1 Week of Treatment (time frame: Baseline, 1 Week). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00186017.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 May 2017.