Bipolar II DisorderPhase 4NCT00186043
Seroquel in the Treatment of Dysphoric Hypomania in Bipolar II
A Phase 4 study testing Quetiapine/Seroquel in people with Bipolar II Disorder, run by Stanford University at 1 site in United States.
Trial summary
1. The primary objective of this study is to examine the efficacy of quetiapine (Seroquel) in treatment of dysphoric hypomania in patients with Bipolar II disorder. 2. To evaluate the utility of Seroquel add-on treatment to decrease mixed depressive and hypomanic symptoms. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar II Disorder
- What is being tested?
- Quetiapine/Seroquel
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 55 participants
- Where
- 1 siteUnited States
- Study dates
- Aug 2008to Aug 2011
- 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 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Must meet criteria for DSM-IV TR diagnosis of bipolar II disorder, as assessed by the structured clinical interview mood modules (SCID) (First et al., 1996).
- Must be hypomanic as rated by a >12 on the YMRS on two consecutive visits 1-3 days apart. And meet DSM IV TR criteria for hypomania
- Must be experiencing depressive symptoms as rated by > 14 on the MADRS rated at two consecutive visits 1-3 days apart and experiencing depressive symptoms for at least a seven-day period.
- Must be on stable medication regimens for at least two weeks, or on no medication at study entry.
- Must be men or women age 18-65 years of age.
- Must be able to give informed consent.
- Must be able to comprehend and satisfactorily comply with protocol requirements.
- If sexually active, females of child-bearing potential must be using a reliable method of contraception, which includes hormonal contraceptives, double-barrier methods (e.g., condom and foam, condom and diaphragm), intrauterine devices (IUD), or tubal ligation. Oral hormonal contraception is allowed as long as no other medications are being used that could decrease hormone levels and put the patient at risk for developing pregnancy.
Who cannot join
- Receiving any atypical antipsychotics (washout period to be determined by treating psychiatrist)
- Receiving recognized antidepressant medication (within five half-lives), including serotonin reuptake inhibitors, venlafaxine, bupropion, or nefazodone.
- Receiving carbamazepine (within five half-lives).
- Experienced a hypomanic episode judged to be a direct physiological consequence of any medical condition or treatment, including neurological disorders, cardiovascular disease, metabolic or autoimmune conditions.
- Evidence that the patient is likely to need additional concomitant medical therapy during the trial.
- Participated in another trial of an investigational drug/device *or received clozapine within 30 days prior to baseline.
Show all 13Show fewer
- Known hypersensitivity to Seroquel or any of its components.
- Known intolerability or past history of ineffectiveness of Seroquel.
- Met DSM-IV TR criteria for any substance or alcohol abuse or dependence disorder within the past month.
- History or evidence of unstable medical condition or known clinically significant abnormal laboratory results.
- Known or suspected chronic infectious disease including HIV or hepatitis.
- Women who are currently pregnant or desire to become pregnant during the study or women nursing an infant.
- Meet criteria for antisocial personality disorder.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Double-Blind, Placebo-Controlled Trial of Seroquel for the Treatment of Dysphoric Hypomania in Bipolar II Patients
- The primary objective of this study is to examine the efficacy of quetiapine (Seroquel) in treatment of dysphoric hypomania in patients with Bipolar II disorder.
- To evaluate the utility of Seroquel add-on treatment to decrease mixed depressive and hypomanic symptoms.
Read the detailed description
Bipolar disorder is recognized as a severe and treatment-refractory illness. Recent work from multiple research centers in both Europe and the U.S. have found the percentage of patients experiencing hypomania that are also experiencing depressive symptoms is substantial. In a recent Stanley Foundation Bipolar Network study, it was found that 60% of all visits with at least moderate hypomania were associated with depressive symptoms. It is generally agreed that patients experiencing mixed states or combinations of mania with depressive symptoms are less responsive to older treatments such as lithium (Swann et al., 1997). We propose evaluating the response to Seroquel add-on versus placebo add-on for those patients experiencing hypomania and depressive symptoms, either simultaneously or closely juxtaposed within a 2-3 day period.
Bipolar II (BDII) patients make up a substantial percentage of patients with bipolar disorder, estimated conservatively at 0.5% of the US population and, with somewhat more liberal definitions of hypomania minimum duration, in Europe at 1% or greater. Importantly, few to virtually no recent treatment trials of high quality have been undertaken in BDII. Treatment guidelines and algorithms for bipolar disorder have been unable to specify defined treatments for BDII due to the lack of studies. Juxtaposed to the limits of controlled data, preliminary case series and clinical experience support atypical antipsychotics will be helpful for BDII patients. Thus the impact is high for a placebo controlled study of Seroquel in BDII.
We believe that this study is important to undertake because of the limited controlled data available for the treatment and management of patients with bipolar II disorder in outpatient settings. Numerous placebo-controlled monotherapy studies have been completed in inpatient settings for bipolar I, many leading to FDA submissions for registration. Maintenance trials are underway or are being developed for bipolar I disorder. There are no medications specifically approved for use in bipolar II patients at this time.
Additionally, the initial trials for the registration of Seroquel for bipolar disorder did not include patients with mixed symptoms. Clear cut-offs were provided in order to minimize the likelihood that patients with mixed symptoms would enter these trials. Thus, the trial proposed will provide data useful to the clinician in a real world setting, as well as provide data in an area not previously covered by the trial registration studies. We hypothesize that Seroquel will be effective to treat such symptoms in patients with BDII.
A clinically important and ground breaking aspect of the proposed trial is the focus on patients with bipolar II disorder. There is a paucity of data available to evaluate the use of atypical antipsychotics in patients with bipolar II disorder. Preliminary data of any sort in this area will be clinically useful, set the stage for larger more definitive trials, and translate readily into practice.
- Conditions
- Bipolar II Disorder
- Being tested
- Quetiapine/Seroquel, Placebo
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Quetiapine/SeroquelDrug
Quetiapine/Seroquel
PlaceboDrug
Placebo
| Study group | Role | What they receive |
|---|---|---|
| Quetiapine/Seroquel | Experimental | Quetiapine/Seroquel up to 800 mg/day Receives: Drug: Quetiapine/Seroquel |
| Placebo | Placebo comparator | Placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants With >=50% Improvement From Baseline in Clinical Global Impression for Bipolar Disorders Overall Severity
0-7 scale: rated on the following seven-point scale:) 0=not assessed, 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients.
This rating is based upon observed and reported symptoms, behavior, and function in the past seven days.
Measured: Baseline and 8 weeks
Percentage of Participants With Clinical Global Impression for Bipolar Disorders Overall Severity Remission (Score <=2 at Week 8)
0-7 scale: rated on the following seven-point scale:) 0=not assessed, 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients.
This rating is based upon observed and reported symptoms, behavior, and function in the past seven days.
Measured: Week 8
Secondary outcomes (1)
Percentage of Participants With 50% Improvement From Baseline in Both Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) Scores
MADRS assesses change from baseline to endpoint. Higher score indicates more severe depression; each item yields a score of 0 to 6. Overall score ranges: 0 to 60. Questions following symptoms 1. Apparent sadness 2. Reported sadness 3. Inner tension 4. Reduced sleep 5. Reduced appetite 6. Concentration difficulties 7. Lassitude 8. Inability to feel 9. Pessimistic thoughts 10. Suicidal thoughts. Cutoff points:0 to 6- normal/symptom absent; 7 to 19- mild depression; 20 to 34- moderate depression; >34- severe depression. YMRS:a 11-item clinician-admin instrument assesses severity of mania. Symptoms rated: Elevated mood, Increased motor activity/energy, Sexual interest, Sleep, irritability, Speech, language/thought disorder, Content, Disruptive/aggressive behavior, Appearance, Insight. Each composed of five explicitly defined levels of severity. Severity ratings based on patient's subjective report of clinical condition during past 48 hours and clinician's observations.
Measured: Baseline and 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2005 (estimated)
- Study startAug 2008
- Primary completionAug 2011
- Study completionAug 2011
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bipolar II 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
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 55 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Terrence Ketter, Stanford University
- Investigators
- Terence Ketter, MD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00186043
- Sponsor's protocol ID
- 79739
- Status last verified
- Sep 2017
- First submitted
- 12 Sep 2005
- Last updated
- 27 Sep 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- Individual data sharing
- No
Publications
Suppes T, Ketter TA, Gwizdowski IS, Dennehy EB, Hill SJ, Fischer EG, Snow DE, Gonzalez R, Sureddi S, Shivakumar G, Cosgrove VE. First controlled treatment trial of bipolar II hypomania with mixed symptoms: quetiapine versus placebo. J Affect Disord. 2013 Aug 15;150(1):37-43. doi: 10.1016/j.jad.2013.02.031. Epub 2013 Mar 19.
PubMed 23521871
Study at a glance
From the registry record, last updated by the sponsor on 27 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Double-Blind, Placebo-Controlled Trial of Seroquel for the Treatment of Dysphoric Hypomania in Bipolar II Patients
- ClinicalTrials.gov ID
- NCT00186043
- Acronym / sponsor ID
- 79739
- Conditions
- Bipolar II Disorder
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 55 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Aug 2008
- Primary completion
- Aug 2011 (actual)
- Study completion
- Aug 2011 (actual)
- First posted
- 16 Sep 2005 (estimated)
- Results
- Posted 27 Sep 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
- The primary objective of this study is to examine the efficacy of quetiapine (Seroquel) in treatment of dysphoric hypomania in patients with Bipolar II disorder.
- To evaluate the utility of Seroquel add-on treatment to decrease mixed depressive and hypomanic symptoms.
Detailed description
Bipolar disorder is recognized as a severe and treatment-refractory illness. Recent work from multiple research centers in both Europe and the U.S. have found the percentage of patients experiencing hypomania that are also experiencing depressive symptoms is substantial. In a recent Stanley Foundation Bipolar Network study, it was found that 60% of all visits with at least moderate hypomania were associated with depressive symptoms. It is generally agreed that patients experiencing mixed states or combinations of mania with depressive symptoms are less responsive to older treatments such as lithium (Swann et al., 1997). We propose evaluating the response to Seroquel add-on versus placebo add-on for those patients experiencing hypomania and depressive symptoms, either simultaneously or closely juxtaposed within a 2-3 day period.
Bipolar II (BDII) patients make up a substantial percentage of patients with bipolar disorder, estimated conservatively at 0.5% of the US population and, with somewhat more liberal definitions of hypomania minimum duration, in Europe at 1% or greater. Importantly, few to virtually no recent treatment trials of high quality have been undertaken in BDII. Treatment guidelines and algorithms for bipolar disorder have been unable to specify defined treatments for BDII due to the lack of studies. Juxtaposed to the limits of controlled data, preliminary case series and clinical experience support atypical antipsychotics will be helpful for BDII patients. Thus the impact is high for a placebo controlled study of Seroquel in BDII.
We believe that this study is important to undertake because of the limited controlled data available for the treatment and management of patients with bipolar II disorder in outpatient settings. Numerous placebo-controlled monotherapy studies have been completed in inpatient settings for bipolar I, many leading to FDA submissions for registration. Maintenance trials are underway or are being developed for bipolar I disorder. There are no medications specifically approved for use in bipolar II patients at this time.
Additionally, the initial trials for the registration of Seroquel for bipolar disorder did not include patients with mixed symptoms. Clear cut-offs were provided in order to minimize the likelihood that patients with mixed symptoms would enter these trials. Thus, the trial proposed will provide data useful to the clinician in a real world setting, as well as provide data in an area not previously covered by the trial registration studies. We hypothesize that Seroquel will be effective to treat such symptoms in patients with BDII.
A clinically important and ground breaking aspect of the proposed trial is the focus on patients with bipolar II disorder. There is a paucity of data available to evaluate the use of atypical antipsychotics in patients with bipolar II disorder. Preliminary data of any sort in this area will be clinically useful, set the stage for larger more definitive trials, and translate readily into practice.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Quetiapine/Seroquel | Experimental | Drug: Quetiapine/SeroquelQuetiapine/Seroquel up to 800 mg/day |
| Placebo | Placebo comparator | Drug: PlaceboPlacebo |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Must meet criteria for DSM-IV TR diagnosis of bipolar II disorder, as assessed by the structured clinical interview mood modules (SCID) (First et al., 1996).
- Must be hypomanic as rated by a >12 on the YMRS on two consecutive visits 1-3 days apart. And meet DSM IV TR criteria for hypomania
- Must be experiencing depressive symptoms as rated by > 14 on the MADRS rated at two consecutive visits 1-3 days apart and experiencing depressive symptoms for at least a seven-day period.
- Must be on stable medication regimens for at least two weeks, or on no medication at study entry.
- Must be men or women age 18-65 years of age.
Key exclusion criteria (13 listed)
- Receiving any atypical antipsychotics (washout period to be determined by treating psychiatrist)
- Receiving recognized antidepressant medication (within five half-lives), including serotonin reuptake inhibitors, venlafaxine, bupropion, or nefazodone.
- Receiving carbamazepine (within five half-lives).
- Experienced a hypomanic episode judged to be a direct physiological consequence of any medical condition or treatment, including neurological disorders, cardiovascular disease, metabolic or autoimmune conditions.
- Evidence that the patient is likely to need additional concomitant medical therapy during the trial.
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 |
|---|---|---|
| Quetiapine/SeroquelQuetiapine/Seroquel | Drug | Quetiapine/Seroquel |
| PlaceboPlacebo | Drug | Placebo |
Primary outcome
Percentage of Participants With >=50% Improvement From Baseline in Clinical Global Impression for Bipolar Disorders Overall Severity
Time frame: Baseline and 8 weeks
0-7 scale: rated on the following seven-point scale:) 0=not assessed, 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. This rating is based upon observed and reported symptoms, behavior, and function in the past seven days.
Percentage of Participants With Clinical Global Impression for Bipolar Disorders Overall Severity Remission (Score <=2 at Week 8)
Time frame: Week 8
0-7 scale: rated on the following seven-point scale:) 0=not assessed, 1=normal, not at all ill; 2=borderline mentally ill; 3=mildly ill; 4=moderately ill; 5=markedly ill; 6=severely ill; 7=among the most extremely ill patients. This rating is based upon observed and reported symptoms, behavior, and function in the past seven days.
1 secondary outcome
Percentage of Participants With 50% Improvement From Baseline in Both Montgomery Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) Scores
Time frame: Baseline and 8 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Sep 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 23521871Suppes T, Ketter TA, Gwizdowski IS, Dennehy EB, Hill SJ, Fischer EG, Snow DE, Gonzalez R, Sureddi S, Shivakumar G, Cosgrove VE. First controlled treatment trial of bipolar II hypomania with mixed symptoms: quetiapine versus placebo. J Affect Disord. 2013 Aug 15;150(1):37-43. doi: 10.1016/j.jad.2013.02.031. Epub 2013 Mar 19.
- Individual participant dataSharing planned: No
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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 Ketter, MD 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 Quetiapine/Seroquel in people with Bipolar II 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?
The sponsor lists 8 inclusion and 13 exclusion criteria. 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 27 Sep 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 27 Sep 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?
Percentage of Participants With >=50% Improvement From Baseline in Clinical Global Impression for Bipolar Disorders Overall Severity (time frame: Baseline and 8 weeks). The study lists 2 primary outcomes in all. 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 NCT00186043, which also lists 1 linked publication.
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 27 Sep 2017.