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Quetiapine XR for Cognitive and Functional Disability in Clinically Stable Patients With Bipolar Disorder

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00746421
Recruitment Status : Terminated (Sponsor withdrew funding)
First Posted : September 4, 2008
Results First Posted : March 28, 2014
Last Update Posted : April 17, 2014
Duke University
University of Toronto
Information provided by (Responsible Party):
Jeffrey Rakofsky, Emory University

Brief 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 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.

Condition or disease Intervention/treatment Phase
Bipolar Disorder Cognitive Impairment Drug: Quetiapine XR Drug: Placebo Phase 4

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase IV Study of Quetiapine XR Aimed at Disability and Cognitive Impairments.
Study Start Date : January 2010
Actual Primary Completion Date : April 2012
Actual Study Completion Date : April 2012

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Bipolar Disorder
Drug Information available for: Quetiapine

Arm Intervention/treatment
Experimental: 1
Quetiapine XR 200-400 mg/day
Drug: Quetiapine XR
oral doses, 200 mg, 300 mg, 400 mg
Other Name: Seroquel XR

Placebo Comparator: 2
Placebo one pill per day matching 200, 300, or 400 mg
Drug: Placebo
200mg, 300mg or 400mg

Primary Outcome Measures :
  1. 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.

Secondary Outcome Measures :
  1. Brief Assessment of Cognition for Affective Disorders (BAC-A) [ Time Frame: 6 weeks ]
    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).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 65 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  1. Provision of written informed consent
  2. 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).
  3. Females and/or males aged 18-65 years.
  4. 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.
  5. Able to understand and comply with the requirements of the study.
  6. YMDRS score <13.
  7. MADRS score <19.
  8. Currently receiving medication therapy with lithium, valproate, or lamotrigine or any combination thereof. (preference given to lithium and/or valproate).
  9. Clinically stable for 4 weeks prior to study entry, confirmed at week 2.

Exclusion criteria:

  1. Intolerance of quetiapine
  2. Change in mood stabilizer medication or dose in the last 4 weeks, change in antidepressant medication or dose in the last two months.
  3. Current treatment with carbamazepine, stimulants, atomoxetine, or another antipsychotic
  4. Current treatment with norepinephrine reuptake inhibiting antidepressants (Milnacipran, bupropion, paroxetine, duloxetine, venlafaxine, all MAOI's, all TCAs)
  5. Current pregnancy or lactation
  6. Active Anorexia nervosa or Bulimia nervosa in the past six months
  7. History of non-affective psychotic disorders (including schizoaffective disorder)
  8. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others
  9. 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
  10. 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
  11. Administration of a depot antipsychotic injection within one dosing interval (for the depot) before randomisation
  12. 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
  13. Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris, hyperlipidemia, hypertension) as judged by the investigator
  14. Involvement in the planning and conduct of the study
  15. Previous enrolment or randomisation of treatment in the present study.
  16. Participation in another drug trial within 4 weeks prior enrolment into this study or longer in accordance with local requirements
  17. 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.
  18. An absolute neutrophil count (ANC) of < 1.5 x 10^9 per liter

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00746421

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United States, Georgia
Emory University School of Medicine
Atlanta, Georgia, United States, 30322
United States, North Carolina
Duke University
Durham, North Carolina, United States, 27710
Sponsors and Collaborators
Emory University
Duke University
University of Toronto
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Principal Investigator: Jeffrey J Rakofsky, MD Emory University

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Responsible Party: Jeffrey Rakofsky, Assistant Professor of Psychiatry and Behavioral Sciences, Emory University Identifier: NCT00746421    
Other Study ID Numbers: IRB00009874
First Posted: September 4, 2008    Key Record Dates
Results First Posted: March 28, 2014
Last Update Posted: April 17, 2014
Last Verified: March 2014
Keywords provided by Jeffrey Rakofsky, Emory University:
Additional relevant MeSH terms:
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Cognitive Dysfunction
Bipolar Disorder
Cognition Disorders
Neurocognitive Disorders
Mental Disorders
Bipolar and Related Disorders
Quetiapine Fumarate
Antidepressive Agents
Psychotropic Drugs
Antipsychotic Agents
Tranquilizing Agents
Central Nervous System Depressants
Physiological Effects of Drugs