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

Phase 3

Completed

Conditions: Borderline Personality Disorder

Interventions: Drug: quetiapine extended-release
Drug: Placebo

Registration Number: NCT00880919

Lead Sponsor: University of Minnesota

Brief Summary: 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: 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:

1. 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.

2. 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).

3. 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 95

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	quetiapine extended-release	Seroquel XR 150mg oral tablets taken daily for 8 weeks.
3	Placebo	Equivalent number of placebo oral tablets taken daily for 8 weeks.
2	quetiapine extended-release	Seroquel XR 300mg oral tablets taken daily for 8 weeks.

Primary Outcome Measures

Name	Time	Method
Borderline Evaluation of Severity Over Time (BEST)	Baseline to 8 weeks	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).
Overt Aggression Scale - Modified (OAS-M)	Change from Baseline Overt Aggression Scale - Modified to 8 weeks	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.
Montgomery-Åsberg Depression Rating Scale (MADRS)	baseline to 8 weeks	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.
Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD)	baseline, weekly until week 8	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.
Barratt Impulsiveness Scale (BIS)	Change in Impulsiveness from Baseline to 8 weeks	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.
Symptom Checklist -90-Revised (SCL-90-R)	Change in psychological problems and symptoms from Baseline to 8 weeks	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
Global Assessment of Functioning Scale (GAF)	Change in Global Assessment of Functioning from Baseline to 8 weeks	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
Young Mania Rating Scale (YMS)	Change in manic symptoms from Baseline to 8 weeks	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
Sheehan Disability Scale (SDS)	Change in functional impairment from Baseline to 8 weeks	Three self-rated items, on a scale of 0-10. 0 is unimpaired 10 is highly impaired This measures functional impairment

Secondary Outcome Measures

Name	Time	Method

Trial Locations

Locations (3): University of Iowa, Department of Psychiatry
🇺🇸
Iowa City, Iowa, United States
McLean Hospital, Harvard Medical School, Department of Psychiatry
🇺🇸
Belmont, Massachusetts, United States
University of Minnesota Medical Center, Fairview Riverside
🇺🇸
Minneapolis, Minnesota, United States