Seroquel Extended Release (XR) for the Management of Borderline Personality Disorder (BPD)

Study Overview
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Brief Summary
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The Primary objective of this study is to evaluate Seroquel XR in the treatment of borderline personality disorder (BPD). As in many initial randomized control trials, the study will be of relatively short duration - 8 weeks - to assess effectiveness and safety while maximizing retention. The specific aim is to determine if Seroquel XR is superior to placebo. The primary outcome measure will be a statistically significant difference between Seroquel XR compared to placebo on the Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD), an objective rating scale that addresses the severity of Diagnostic and Statistical Manual of Mental Disorders, 4th Edition (DSM-IV) symptoms of the illness. As there is the recent development of an extended release form of Seroquel (Seroquel XR) (Schulz et al. 2007), the new compound may offer several advantages in this study. Therefore, the hypothesis of this study is that both doses of Seroquel XR (see below) will be superior to placebo in an 8-week randomized trial as assessed by the ZAN-BPD. To achieve the Primary Objective of this study, two doses of Seroquel XR will be tested - 150 mg/d and 300 mg/d. Thus, the study will be able to assess the effect of Seroquel XR compared to placebo and to explore a dose effect.

Detailed Description
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The secondary objectives in this study are aimed at answering further questions regarding symptom assessments, dosing strategies, and safety. The specific secondary objectives are listed below: Response rate: In previous studies using the ZAN-BPD, response was defined as a 50% reduction of ZAN-BPD scores. Response rates will be compared between Seroquel XR and placebo. Other Symptom Measures: Over the last twenty years, other rating scales of a general nature have been used to assess BPD patients in clinical trials. To fully assess the patients as they progress through the study, the following scales will be administered: Symptom Checklist 90 - Revised (SCL-90 R), Montgomery Asberg Depression Rating Scale (MADRS), Barratt Impulsivity Scale (BIS), Schedule for Interviewing Borderlines (SIB), Overt Aggression Scale - Modified (OAS-M), Young Mania Rating Scale (YMRS), the Borderline Evaluation of Severity over Time (BEST), and the Global Assessment of Function (GAF). Side-Effects: To be able to report the safety of Seroquel XR for BPD, a combination of objective and subjective measures will be employed. Objectively, weight, height (and Body Mass Index (BMI)), prolactin, glucose, cholesterol and triglycerides will be assessed at baseline and endpoint. Objective ratings of movement side effects will be performed using Simpson Angus Scale (SAS) (Simpson and Angus 1970), Barnes Akathisia Scale (BAS) (Barnes 1989), and Abnormal Involuntary Movement Scale (AIMS) (Guy 1976), and at baseline and endpoint. Regarding possible side effects reported by patients, their reports of headache, somnolence, and other experiences will be tabulated. Secondary objective data will be analyzed as continuous variable data over the time of the study or, when appropriate, comparisons of baseline to endpoint will be made.

Official Title
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Seroquel XR for the Management of Borderline Personality Disorder (BPD)

Conditions
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Borderline Personality Disorder

Intervention / Treatment
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* Drug: quetiapine extended-release
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Consent A diagnosis of borderline personality disorder (301.83) All subjects will have a ZAN-BPD greater or equal to 9 at randomization. Males and females aged 18-45 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 enrollment Able to understand and comply with the requirements of the study Exclusion Criteria: Pregnancy or lactation Any DSM-IV Axis I disorder not defined in the inclusion criteria. The patients with BPD may not have bipolar I disorder, schizophrenia, schizoaffective disorder, delirium, or dementia. Neither may they have current DSM-IV substance dependence. Patients who, in the opinion of the investigator, pose an imminent risk of suicide or a danger to self or others Known intolerance or lack of response to quetiapine fumarate, as judged by the investigator Use of any of the following cytochrome P450 3A4 inhibitors in the 14 days preceding enrollment 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 randomization Substance or alcohol dependence at enrollment (except dependence in full remission, and except for caffeine or nicotine dependence), as defined by DSM-IV criteria Opiates, amphetamine, barbiturate, cocaine, cannabis, or hallucinogen abuse by DSM-IV criteria within 4 weeks prior to enrollment Medical conditions that would affect absorption, distribution, metabolism, or excretion of study treatment Unstable or inadequately treated medical illness (e.g. diabetes, angina pectoris, hypertension, congestive heart failure) as judged by the investigator Involvement in the planning and conduct of the study Previous enrollment or randomization of treatment in the present study. Participation in another drug trial within 4 weeks prior enrollment into this study or longer in accordance with local requirements Unstable Diabetes Mellitus An absolute neutrophil count (ANC) of 1.5 x 109 per liter Past history of lack of response to an atypical antipsychotic medication or substantial previous side effects will be cause for exclusion. Any medical illness that would interfere with conduct of the study will be cause for exclusion. Pregnant or lactating women and women of childbearing potential not using medically accepted means of contraception.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Seroquel XR 150mg oral tablets taken daily for 8 weeks. | Drug: quetiapine extended-release<br>* Seroquel XR 150mg/day vs Seroquel XR 300mg/day vs Placebo<br>* Other names: Seroquel XR;|
| Active Comparator: 2<br>Seroquel XR 300mg oral tablets taken daily for 8 weeks. | Drug: quetiapine extended-release<br>* Seroquel XR 150mg/day vs Seroquel XR 300mg/day vs Placebo<br>* Other names: Seroquel XR;|
| Placebo Comparator: 3<br>Equivalent number of placebo oral tablets taken daily for 8 weeks. | Drug: Placebo<br>* Seroquel XR 150mg/day vs Seroquel XR 300mg/day vs Placebo<br>* Other names: quetiapine extended-release;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) | This is an assessment of change in DSM-IV borderline psychopathology. Consisting of nine criteria rated on a five-point anchored rating scale of 0 to 4, yielding a total score of 0 to 36. 0 being the best and 4 meaning the worse. | baseline, weekly until week 8 | 
| Montgomery-Åsberg Depression Rating Scale (MADRS) | Nine criteria rated on a six-point anchored rating scale of 0 to 6, yielding a total score of 0 to 60. O is the least and 6 is the highest 0 to 6 - normal /symptom absent 7 to 19 - mild depression 20 to 34 - moderate depression >34 - severe depression. | baseline to 8 weeks | 
| Borderline Evaluation of Severity Over Time (BEST) | Scale including 15 items and three subscales. All items are rated on a Likert-like scale. A correction factor of 15 is added to yield the final score which can range from 12 (best) to 72 (worst). | Baseline to 8 weeks | 
| Overt Aggression Scale - Modified (OAS-M) | Four part behavior rating scale designed to measure four types of aggressive behavior as witnessed in the past week. Each section consists of five questions. Total scores on the MOAS range from 0-40. 0 is the best and 40 is the worst of symptoms Reduction in scores shows a change of symptoms. | Change from Baseline Overt Aggression Scale - Modified to 8 weeks | 
| Global Assessment of Functioning Scale (GAF) | Numeric scale (1 through 100) used by mental health clinicians and physicians to rate subjectively the social, occupational, and psychological functioning of adults. 100 is the highest level of functioning. O is the least functional | Change in Global Assessment of Functioning from Baseline to 8 weeks | 
| Barratt Impulsiveness Scale (BIS) | 30-item self-report questionnaire, that is scored to yield a total score, three second-order factors, and six first-order factors. patients rate the questions 1-4 1 being the least and 4 being the most. | Change in Impulsiveness from Baseline to 8 weeks | 
| Symptom Checklist -90-Revised (SCL-90-R) | 90 items measured on a Likert scale via self-report. Scale is 0-5 stating 0= strongly disagree and 5 is Strongly agree Measures psychological problems and symptoms | Change in psychological problems and symptoms from Baseline to 8 weeks | 
| Young Mania Rating Scale (YMS) | Eleven-item multiple choice diagnostic questionnaire, yielding total scores of 0-60. 0-4 rating 0-being least likely and 4 being most likely This scale assess manic symptoms | Change in manic symptoms from Baseline to 8 weeks | 
| Sheehan Disability Scale (SDS) | Three self-rated items, on a scale of 0-10. 0 is unimpaired 10 is highly impaired This measures functional impairment | Change in functional impairment from Baseline to 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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BPD, Borderline Personality Disorder, Seroquel, Seroquel XR, quetiapine, quetiapine extended-release