Bipolar DisorderPhase 4NCT00746421
Quetiapine XR for Cognitive and Functional Disability in Clinically Stable Patients With Bipolar Disorder
A Phase 4 study testing Quetiapine XR in people with Bipolar Disorder and Cognitive Impairment, run by Emory University at 2 sites in United States.
Trial summary
Quetiapine has been reported to have beneficial cognitive effects in several randomized controlled trials in schizophrenia. It has not yet been studied in bipolar disorder, but promising results from the use of extended release quetiapine for the maintenance treatment of bipolar disorder suggests that its cognitive… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Bipolar Disorder, Cognitive Impairment
- What is being tested?
- Quetiapine XR
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 32 participants
- Where
- 2 sitesUnited States
- Study dates
- Jan 2010to Apr 2012
- 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
- Provision of written informed consent
- A primary diagnosis of Bipolar disorder type 1 or 2, with a definite history of manic or hypomanic episodes by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV).
- Females and/or males aged 18-65 years.
- Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at enrolment.
- Able to understand and comply with the requirements of the study.
- YMDRS score <13.
Show all 9Show fewer
- MADRS score <19.
- Currently receiving medication therapy with lithium, valproate, or lamotrigine or any combination thereof. (preference given to lithium and/or valproate).
- Clinically stable for 4 weeks prior to study entry, confirmed at week 2.
Who cannot join
- Intolerance of quetiapine
- Change in mood stabilizer medication or dose in the last 4 weeks, change in antidepressant medication or dose in the last two months.
- Current treatment with carbamazepine, stimulants, atomoxetine, or another antipsychotic
- Current treatment with norepinephrine reuptake inhibiting antidepressants (Milnacipran, bupropion, paroxetine, duloxetine, venlafaxine, all MAOI's, all TCAs)
- Current pregnancy or lactation
- Active Anorexia nervosa or Bulimia nervosa in the past six months
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- History of non-affective psychotic disorders (including schizoaffective disorder)
- Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
- Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrolment including but not limited to: ketoconazole, itraconazole, fluconazole, erythromycin, clarithromycin, troleandomycin, indinavir, nelfinavir, ritonavir, fluvoxamine and saquinavir
- Use of any of the following cytochrome P450 inducers in the 14 days preceding enrollment including but not limited to: phenytoin, carbamazepine, barbiturates, rifampin, St. John's Wort, and glucocorticoids
- Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation
- Active Substance/ alcohol abuse or dependence in the past three months before enrollment ( except for caffeine or nicotine dependence), as defined by DSM-IV criteria Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment
- Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris, hyperlipidemia, hypertension) as judged by the investigator
- Involvement in the planning and conduct of the study
- Previous enrolment or randomisation of treatment in the present study.
- Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements
- A patient with Diabetes Mellitus (DM) fulfilling one of the following criteria:
- Unstable DM defined as enrollment glycosylated hemoglobin (HbA1c) >8.5%.
- Admitted to hospital for treatment of DM or DM related illness in past 12 weeks.
- Not under physician care for DM
- Physician responsible for patient's DM care has not indicated that patient's DM is controlled.
- Physician responsible for patient's DM care has not approved patient's participation in the study
- Has not been on the same dose of oral hypoglycaemic drug(s) and/or diet for the 4 weeks prior to randomization. For thiazolidinediones (glitazones) this period should not be less than 8 Weeks.
- Taking insulin whose daily dose on one occasion in the past 4 weeks has been more than 10% above or below their mean dose in the preceding 4 weeks Note: If a diabetic patient meets one of these criteria, the patient is to be excluded even if the treating physician believes that the patient is stable and can participate in the study.
- An absolute neutrophil count (ANC) of < 1.5 x 10^9 per liter
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
Duke University
Durham, North Carolina, 27710
About this study
Official title: Phase IV Study of Quetiapine XR Aimed at Disability and Cognitive Impairments.
Quetiapine has been reported to have beneficial cognitive effects in several randomized controlled trials in schizophrenia. It has not yet been studied in bipolar disorder, but promising results from the use of extended release quetiapine for the maintenance treatment of bipolar disorder suggests that its cognitive benefits could be detected. Moreover, quetiapine has been shown to have direct beneficial effects on performance-based measures of social competence in schizophrenia and to improve quality of life (QoL) in bipolar depression. The investigators propose to study quetiapine augmentation of mood stabilizer monotherapy in clinically stable patients with bipolar disorder. This will be a randomized, placebo controlled trial, with attentional impairments as the primary outcome and other cognitive performance variables and measures of social and everyday living skills, as well as subjective QoL, as the secondary outcomes.
Read the detailed description
In contrast to previous conceptions of bipolar disorder as an illness where cognitive impairments were limited to manic and depressed episodes, it has become clear that cognitive impairments are common in clinically stable bipolar patients.
Quetiapine has been reported to have beneficial cognitive effects in several randomized controlled trials in schizophrenia. It has not yet been studied in bipolar disorder, but promising results from the use of extended release quetiapine for the maintenance treatment of bipolar disorder suggests that its cognitive benefits could be detected. Moreover, quetiapine has been shown to have direct beneficial effects on performance-based measures of social competence in schizophrenia and to improve quality of life (QoL) in bipolar depression. We propose to study quetiapine augmentation of mood stabilizer monotherapy in clinically stable patients with bipolar disorder. This will be a randomized, placebo controlled trial, with attentional impairments as the primary outcome and other cognitive performance variables and measures of social and everyday living skills, as well as subjective QoL, as the secondary outcomes.
An additional possible benefit of quetiapine treatment, and one that is directly relevant to neuropsychological performance, is that of increased activity of cortical norepinephrine (NE). Thus, in studies of cognitive enhancement with quetiapine, examination of cortical NE neet occupancy will be of substantial interest.
General Background: This will be a three site study which will include Emory University (Coordinating site), Duke University, and University of Toronto. We choose to have three sites so that the difficult task of recruiting clinically stable patients with bipolar can be accomplished quickly and the study can be completed within a two-year time frame.
Subjects: We will recruit 100 patients for this study. Fifty percent of them will receive active treatment with quetiapine XR. All participants will meet diagnostic criteria for bipolar I and II disorder and have medical record-based evidence of at least one previous manic or mixed episode. They will be clinically stable, as evidence by meeting criteria for low scores on both the Young Mania Rating Scale (YMRS) and the Montgomery-Asberg Depression rating scale (MADRS). They will also be receiving therapy with mood stabilizers, either lithium or an approved mood stabilizing agent.
Visit Schedule: This is a 10 week study with a six-week active treatment protocol. All interested patients who meet study entry criteria will be screened for stability four and two weeks prior to the baseline assessment. Patients will also be re-assessed for stability at baseline. Patients who fail to meet entry criteria at baseline can come back for a second screening after 2 and 4 weeks.
Throughout treatment, medication adjustments will be limited to changes of less than 25% during this time period.
Assessments: Cognitive assessments will be performed at baseline, week 2 and week 6 of active treatment.
Clinical Assessments will be performed at screening and rescreening, baseline, weeks 2 and 6.
Biological Measures: Bloods for NE net occupancy will be drawn at baseline, week 2, and week 6. Serum levels of quetiapine at all three assessments will also be examined.
Cognitive Assessments:
We will focus our cognitive assessment on the types of cognitive impairments previously reported in bipolar disorder. Our focus will be on attention, episodic memory, processing speed, and working memory. This same instrumentation has proven able to detect sedation as well, so that we can use the results of our assessment to identify any potential adverse sedation effects.
- Conditions
- Bipolar Disorder, Cognitive Impairment
- Being tested
- Quetiapine XR, Placebo
- Keywords
- Cognition, attention, bipolar, disability
- Medical subject headings
- Bipolar Disorder, Cognitive Dysfunction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Quetiapine XRDrug
Also called Seroquel XR
oral doses, 200 mg, 300 mg, 400 mg
PlaceboDrug
200mg, 300mg or 400mg
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Quetiapine XR 200-400 mg/day Receives: Drug: Quetiapine XR |
| 2 | Placebo comparator | Placebo one pill per day matching 200, 300, or 400 mg Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The Continuous Performance Test-Identical Pairs Version
The Continuous Performance Test, Identical Pairs version (CPT-IP) is a cognitive test that requires a subject to respond whenever two identical stimuli appear in a row within a sequence of 150 rapidly flashed trials. The outcome is measured as d' (detection signal) and is dimensionless. Among healthy adult men and women, d' scores ranged from 3.07-4.57 (Chen et al. Schizophrenia Bulletin, 1998; 24(1):163-174). The higher the value the better the performance. The d' is calculated by averaging the d' scores from three trials.
Measured: 6 weeks
Secondary outcomes (1)
Brief Assessment of Cognition for Affective Disorders (BAC-A)
This is a series of neurocognitive tests and includes brief assessments of attention, motor speed, working memory, verbal memory, reasoning and problem solving, verbal fluency, affective interference, and emotion inhibition. The total BAC-A score is represented by a composite T-score which is dimensionless. This is computed by adding up the scores for each trial of a test domain (e.g. verbal memory) within the cognitive battery. Each test domain total is then inputted into a proprietary BAC-A calculator which determines the composite T-scores. A higher score indicates better performance. A study of 404 healthy adults demonstrated a mean composite score of 50 with a standard deviation of 10 (Keefe et al. Schizophrenia Bulletin. 2008; 102: 108-115).
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Sep 2008 (estimated)
- Study startJan 2010
- Primary completionApr 2012
- Study completionApr 2012
Why it stopped: Sponsor withdrew funding
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 Emory 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
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Emory University
- Sponsor type
- University, hospital or other
- Collaborators
- Duke University, University of Toronto
- Responsible party
- Principal investigator, Jeffrey Rakofsky, Emory University
- Investigators
- Jeffrey J Rakofsky, MD, Principal investigator, Emory University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00746421
- Sponsor's protocol ID
- IRB00009874
- Status last verified
- Mar 2014
- First submitted
- 3 Sep 2008
- Last updated
- 17 Apr 2014
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase IV Study of Quetiapine XR Aimed at Disability and Cognitive Impairments.
- ClinicalTrials.gov ID
- NCT00746421
- Acronym / sponsor ID
- IRB00009874
- Conditions
- Bipolar Disorder, Cognitive Impairment
- Keywords
- Cognition, attention, bipolar, disability
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Sponsor withdrew funding
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Emory UniversityUniversity, hospital or other
- Collaborators
- Duke University, University of Toronto
- Study start
- Jan 2010
- Primary completion
- Apr 2012 (actual)
- Study completion
- Apr 2012 (actual)
- First posted
- 4 Sep 2008 (estimated)
- Results
- Posted 28 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Quetiapine has been reported to have beneficial cognitive effects in several randomized controlled trials in schizophrenia. It has not yet been studied in bipolar disorder, but promising results from the use of extended release quetiapine for the maintenance treatment of bipolar disorder suggests that its cognitive benefits could be detected. Moreover, quetiapine has been shown to have direct beneficial effects on performance-based measures of social competence in schizophrenia and to improve quality of life (QoL) in bipolar depression. The investigators propose to study quetiapine augmentation of mood stabilizer monotherapy in clinically stable patients with bipolar disorder. This will be a randomized, placebo controlled trial, with attentional impairments as the primary outcome and other cognitive performance variables and measures of social and everyday living skills, as well as subjective QoL, as the secondary outcomes.
Detailed description
In contrast to previous conceptions of bipolar disorder as an illness where cognitive impairments were limited to manic and depressed episodes, it has become clear that cognitive impairments are common in clinically stable bipolar patients.
Quetiapine has been reported to have beneficial cognitive effects in several randomized controlled trials in schizophrenia. It has not yet been studied in bipolar disorder, but promising results from the use of extended release quetiapine for the maintenance treatment of bipolar disorder suggests that its cognitive benefits could be detected. Moreover, quetiapine has been shown to have direct beneficial effects on performance-based measures of social competence in schizophrenia and to improve quality of life (QoL) in bipolar depression. We propose to study quetiapine augmentation of mood stabilizer monotherapy in clinically stable patients with bipolar disorder. This will be a randomized, placebo controlled trial, with attentional impairments as the primary outcome and other cognitive performance variables and measures of social and everyday living skills, as well as subjective QoL, as the secondary outcomes.
An additional possible benefit of quetiapine treatment, and one that is directly relevant to neuropsychological performance, is that of increased activity of cortical norepinephrine (NE). Thus, in studies of cognitive enhancement with quetiapine, examination of cortical NE neet occupancy will be of substantial interest.
General Background: This will be a three site study which will include Emory University (Coordinating site), Duke University, and University of Toronto. We choose to have three sites so that the difficult task of recruiting clinically stable patients with bipolar can be accomplished quickly and the study can be completed within a two-year time frame.
Subjects: We will recruit 100 patients for this study. Fifty percent of them will receive active treatment with quetiapine XR. All participants will meet diagnostic criteria for bipolar I and II disorder and have medical record-based evidence of at least one previous manic or mixed episode. They will be clinically stable, as evidence by meeting criteria for low scores on both the Young Mania Rating Scale (YMRS) and the Montgomery-Asberg Depression rating scale (MADRS). They will also be receiving therapy with mood stabilizers, either lithium or an approved mood stabilizing agent.
Visit Schedule: This is a 10 week study with a six-week active treatment protocol. All interested patients who meet study entry criteria will be screened for stability four and two weeks prior to the baseline assessment. Patients will also be re-assessed for stability at baseline. Patients who fail to meet entry criteria at baseline can come back for a second screening after 2 and 4 weeks.
Throughout treatment, medication adjustments will be limited to changes of less than 25% during this time period.
Assessments: Cognitive assessments will be performed at baseline, week 2 and week 6 of active treatment.
Clinical Assessments will be performed at screening and rescreening, baseline, weeks 2 and 6.
Biological Measures: Bloods for NE net occupancy will be drawn at baseline, week 2, and week 6. Serum levels of quetiapine at all three assessments will also be examined.
Cognitive Assessments:
We will focus our cognitive assessment on the types of cognitive impairments previously reported in bipolar disorder. Our focus will be on attention, episodic memory, processing speed, and working memory. This same instrumentation has proven able to detect sedation as well, so that we can use the results of our assessment to identify any potential adverse sedation effects.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Quetiapine XRQuetiapine XR 200-400 mg/day |
| 2 | Placebo comparator | Drug: PlaceboPlacebo one pill per day matching 200, 300, or 400 mg |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (9 listed)
- Provision of written informed consent
- A primary diagnosis of Bipolar disorder type 1 or 2, with a definite history of manic or hypomanic episodes by Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV).
- Females and/or males aged 18-65 years.
- Female patients of childbearing potential must be using a reliable method of contraception and have a negative urine human chorionic gonadotropin (HCG) test at enrolment.
- Able to understand and comply with the requirements of the study.
Key exclusion criteria (25 listed)
- Intolerance of quetiapine
- Change in mood stabilizer medication or dose in the last 4 weeks, change in antidepressant medication or dose in the last two months.
- Current treatment with carbamazepine, stimulants, atomoxetine, or another antipsychotic
- Current treatment with norepinephrine reuptake inhibiting antidepressants (Milnacipran, bupropion, paroxetine, duloxetine, venlafaxine, all MAOI's, all TCAs)
- Current pregnancy or lactation
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 XRAlso: Seroquel XRoral doses, 200 mg, 300 mg, 400 mg | Drug | 1 |
| Placebo200mg, 300mg or 400mg | Drug | 2 |
Primary outcome
The Continuous Performance Test-Identical Pairs Version
Time frame: 6 weeks
The Continuous Performance Test, Identical Pairs version (CPT-IP) is a cognitive test that requires a subject to respond whenever two identical stimuli appear in a row within a sequence of 150 rapidly flashed trials. The outcome is measured as d' (detection signal) and is dimensionless. Among healthy adult men and women, d' scores ranged from 3.07-4.57 (Chen et al. Schizophrenia Bulletin, 1998; 24(1):163-174). The higher the value the better the performance. The d' is calculated by averaging the d' scores from three trials.
1 secondary outcome
Brief Assessment of Cognition for Affective Disorders (BAC-A)
Time frame: 6 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2014.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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.
Jeffrey J Rakofsky, MD principal investigator
Emory University
2 sites 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 XR in people with Bipolar Disorder and Cognitive Impairment, run by Emory University at 2 sites 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 9 inclusion and 25 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: stopped early, as of the sponsor's last update on 17 Apr 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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 28 Mar 2014). 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?
The Continuous Performance Test-Identical Pairs Version (time frame: 6 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 17 Apr 2014.