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

Condition(s) targeted: Borderline Personality Disorder

Intervention: quetiapine extended-release (Drug); Placebo (Drug)

Phase: Phase 3

Status: Active, not recruiting

Sponsored by: University of Minnesota - Clinical and Translational Science Institute

Official(s) and/or principal investigator(s):
S. Charles Schulz, MD, Principal Investigator, Affiliation: University of Minnesota - Clinical and Translational Science Institute

The Primary objective of this study is to evaluate Seroquel XR in the treatment of BPD. As

in many initial RCTs, 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 ZAN-BPD, an objective rating scale that addresses the severity of 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.

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

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome: The Primary objective of this study is to determine if Seroquel XR is superior to placebo. The primary outcome measure will be a statistically significant difference between Seroquel XR.

Secondary outcome: To be able to report the safety of Seroquel XR for BPD. Objectively, weight, height (and BMI), prolactin, glucose, cholesterol and triglycerides will be assessed at baseline and endpoint.

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 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.

Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Both.

Criteria:

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.

University of Iowa, Department of Psychiatry, Iowa City, Iowa 52242, United States

McLean Hospital, Harvard Medical School, Department of Psychiatry, Belmont, Massachusetts 02478, United States

University of Minnesota Medical Center, Fairview Riverside, Minneapolis, Minnesota 55454, United States

Starting date: June 2008
Last updated: February 1, 2013