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

Primary Purpose

Borderline Personality Disorder

Status

Completed

Phase

Phase 3

Locations

United States

Study Type

Interventional

Intervention

quetiapine extended-release

Placebo

About this trial

This is an interventional treatment trial for Borderline Personality Disorder focused on measuring Borderline Personality Disorder, BPD, Seroquel, Seroquel XR, quetiapine, quetiapine extended-release

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

University of Iowa, Department of Psychiatry
McLean Hospital, Harvard Medical School, Department of Psychiatry
University of Minnesota Medical Center, Fairview Riverside

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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.

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.

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).

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.

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

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.

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

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

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

Secondary Outcome Measures

Full Information

NCT ID

NCT00880919

First Posted

April 10, 2009

Last Updated

January 26, 2017

Sponsor

University of Minnesota

Collaborators

AstraZeneca, University of Iowa, Mclean Hospital

1. Study Identification

Unique Protocol Identification Number

NCT00880919

Brief Title

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

2. Study Status

Record Verification Date

January 2017

Overall Recruitment Status

Completed

Study Start Date

June 2008 (undefined)

Primary Completion Date

March 2013 (Actual)

Study Completion Date

March 2013 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

University of Minnesota

Collaborators

AstraZeneca, University of Iowa, Mclean Hospital

4. Oversight

Data Monitoring Committee

Yes

5. Study Description

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: 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Borderline Personality Disorder

Keywords

Borderline Personality Disorder, BPD, Seroquel, Seroquel XR, quetiapine, quetiapine extended-release

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 3

Interventional Study Model

Parallel Assignment

Masking

ParticipantCare ProviderInvestigator

Allocation

Randomized

Enrollment

95 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Arm Type

Active Comparator

Arm Description

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

Arm Title

Arm Type

Active Comparator

Arm Description

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

Arm Title

Arm Type

Placebo Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

quetiapine extended-release

Other Intervention Name(s)

Seroquel XR

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Placebo

Other Intervention Name(s)

quetiapine extended-release

Intervention Description

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

Primary Outcome Measure Information:

Title

Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD)

Description

Time Frame

baseline, weekly until week 8

Title

Montgomery-Åsberg Depression Rating Scale (MADRS)

Description

Time Frame

baseline to 8 weeks

Title

Borderline Evaluation of Severity Over Time (BEST)

Description

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).

Time Frame

Baseline to 8 weeks

Title

Overt Aggression Scale - Modified (OAS-M)

Description

Time Frame

Change from Baseline Overt Aggression Scale - Modified to 8 weeks

Title

Global Assessment of Functioning Scale (GAF)

Description

Time Frame

Change in Global Assessment of Functioning from Baseline to 8 weeks

Title

Barratt Impulsiveness Scale (BIS)

Description

Time Frame

Change in Impulsiveness from Baseline to 8 weeks

Title

Symptom Checklist -90-Revised (SCL-90-R)

Description

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

Time Frame

Change in psychological problems and symptoms from Baseline to 8 weeks

Title

Young Mania Rating Scale (YMS)

Description

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

Time Frame

Change in manic symptoms from Baseline to 8 weeks

Title

Sheehan Disability Scale (SDS)

Description

Three self-rated items, on a scale of 0-10. 0 is unimpaired 10 is highly impaired This measures functional impairment

Time Frame

Change in functional impairment from Baseline to 8 weeks

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Maximum Age & Unit of Time

45 Years

Accepts Healthy Volunteers

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.

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

S. Charles Schulz, MD

Organizational Affiliation

University of Minnesota

Official's Role

Principal Investigator

Facility Information:

Facility Name

University of Iowa, Department of Psychiatry

City

Iowa City

State/Province

Iowa

ZIP/Postal Code

52242

Country

United States

Facility Name

McLean Hospital, Harvard Medical School, Department of Psychiatry

City

Belmont

State/Province

Massachusetts

ZIP/Postal Code

02478

Country

United States

Facility Name

University of Minnesota Medical Center, Fairview Riverside

City

Minneapolis

State/Province

Minnesota

ZIP/Postal Code

55454

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

36375174

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.

Results Reference

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

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