Clinical trial NCT00880919: Seroquel Extended Release (XR) for the Management of Borderline Personality Disorder (BPD)
Official title: Seroquel XR for the Management of Borderline Personality Disorder (BPD)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Borderline Personality Disorder
Keywords: Borderline Personality Disorder
BPD
Seroquel
Seroquel XR
quetiapine
quetiapine extended-release
Lead sponsor: University of Minnesota
Sponsor class: OTHER
Collaborators: name: AstraZeneca
name: University of Iowa
name: Mclean Hospital
First posted: 2009-04-14
Enrollment: 95
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

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.

Primary outcomes:
measure: Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD)
timeFrame: baseline, weekly until week 8
measure: Montgomery-Åsberg Depression Rating Scale (MADRS)
timeFrame: baseline to 8 weeks
measure: Borderline Evaluation of Severity Over Time (BEST)
timeFrame: Baseline to 8 weeks
measure: Overt Aggression Scale - Modified (OAS-M)
timeFrame: Change from Baseline Overt Aggression Scale - Modified to 8 weeks
measure: Global Assessment of Functioning Scale (GAF)
timeFrame: Change in Global Assessment of Functioning from Baseline to 8 weeks
measure: Barratt Impulsiveness Scale (BIS)
timeFrame: Change in Impulsiveness from Baseline to 8 weeks
measure: Symptom Checklist -90-Revised (SCL-90-R)
timeFrame: Change in psychological problems and symptoms from Baseline to 8 weeks
measure: Young Mania Rating Scale (YMS)
timeFrame: Change in manic symptoms from Baseline to 8 weeks
measure: Sheehan Disability Scale (SDS)
timeFrame: Change in functional impairment from Baseline to 8 weeks
Secondary outcomes:
Other outcomes:
Locations:
city: Iowa City
country: United States
facility: University of Iowa, Department of Psychiatry
state: Iowa
city: Belmont
country: United States
facility: McLean Hospital, Harvard Medical School, Department of Psychiatry
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center, Fairview Riverside
state: Minnesota
Study officials:
affiliation: University of Minnesota
name: S. Charles Schulz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.