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

This study has been terminated.
(Sponsor withdrew funding)
Sponsor:
Collaborators:
Duke University
University of Toronto
Information provided by (Responsible Party):
Jeffrey Rakofsky, Emory University
ClinicalTrials.gov Identifier:
NCT00746421
First received: September 3, 2008
Last updated: March 31, 2014
Last verified: March 2014
  Purpose

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 Intervention Phase
Bipolar Disorder
Cognitive Impairment
Drug: Quetiapine XR
Drug: Placebo
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Phase IV Study of Quetiapine XR Aimed at Disability and Cognitive Impairments.

Resource links provided by NLM:


Further study details as provided by Emory University:

Primary Outcome Measures:
  • The Continuous Performance Test-Identical Pairs Version [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    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:
  • Brief Assessment of Cognition for Affective Disorders (BAC-A) [ Time Frame: 6 weeks ] [ Designated as safety issue: No ]
    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).


Enrollment: 32
Study Start Date: January 2010
Study Completion Date: April 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00746421

Locations
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
Investigators
Principal Investigator: Jeffrey J Rakofsky, MD Emory University
  More Information

No publications provided

Responsible Party: Jeffrey Rakofsky, Assistant Professor of Psychiatry and Behavioral Sciences, Emory University
ClinicalTrials.gov Identifier: NCT00746421     History of Changes
Other Study ID Numbers: IRB00009874
Study First Received: September 3, 2008
Results First Received: September 13, 2013
Last Updated: March 31, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Emory University:
Cognition
attention
bipolar
disability

Additional relevant MeSH terms:
Bipolar Disorder
Cognition Disorders
Disease
Affective Disorders, Psychotic
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Mood Disorders
Pathologic Processes
Quetiapine
Antipsychotic Agents
Central Nervous System Agents
Central Nervous System Depressants
Pharmacologic Actions
Physiological Effects of Drugs
Psychotropic Drugs
Therapeutic Uses
Tranquilizing Agents

ClinicalTrials.gov processed this record on November 23, 2014