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

NCT ID: NCT00880919

Last Updated: 2017-03-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 95 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-06-30
• Study Completion Date: 2013-03-31

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.

Conditions

Borderline Personality Disorder

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

1

Seroquel XR 150mg oral tablets taken daily for 8 weeks.

Group Type: ACTIVE_COMPARATOR

quetiapine extended-release

Intervention Type: DRUG

Seroquel XR 150mg/day vs Seroquel XR 300mg/day vs Placebo

2

Seroquel XR 300mg oral tablets taken daily for 8 weeks.

Group Type: ACTIVE_COMPARATOR

quetiapine extended-release

Intervention Type: DRUG

Seroquel XR 150mg/day vs Seroquel XR 300mg/day vs Placebo

3

Equivalent number of placebo oral tablets taken daily for 8 weeks.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Seroquel XR 150mg/day vs Seroquel XR 300mg/day vs Placebo

Interventions

quetiapine extended-release

Seroquel XR 150mg/day vs Seroquel XR 300mg/day vs Placebo

Intervention Type: DRUG

Placebo

Seroquel XR 150mg/day vs Seroquel XR 300mg/day vs Placebo

Intervention Type: DRUG

Other Intervention Names

Seroquel XR; quetiapine extended-release

Eligibility 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

• 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.

Exclusion Criteria

• Pregnancy or lactation

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

AstraZeneca

INDUSTRY

Sponsor Role: collaborator

University of Iowa

OTHER

Sponsor Role: collaborator

Mclean Hospital

OTHER

Sponsor Role: collaborator

University of Minnesota

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

S. Charles Schulz, MD

Role: PRINCIPAL_INVESTIGATOR

University of Minnesota

Locations

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

Countries

United States

References

Stoffers-Winterling JM, Storebo OJ, Pereira Ribeiro J, Kongerslev MT, Vollm BA, Mattivi JT, Faltinsen E, Todorovac A, Jorgensen MS, Callesen HE, Sales CP, Schaug JP, Simonsen E, Lieb K. Pharmacological interventions for people with borderline personality disorder. Cochrane Database Syst Rev. 2022 Nov 14;11(11):CD012956. doi: 10.1002/14651858.CD012956.pub2.

Reference Type: DERIVED

PMID: 36375174 (View on PubMed)

Other Identifiers

IRUSQUET0454

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

0709M16844

Identifier Type: -

Identifier Source: org_study_id