Brexpiprazole in Borderline Personality Disorder

March 16, 2022 updated by: University of Chicago

A Double-Blind, Placebo-Controlled Study of Brexpiprazole in the Treatment of Borderline Personality Disorder.

The primary objective of the proposed study is to evaluate the safety and efficacy of Brexpiprazole in adults with borderline personality disorder (BPD). The hypothesis to be tested is that brexpiprazole will be more effective and well tolerated in adults with BPD compared to placebo. The proposed study will provide needed data on the treatment of a disabling disorder.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

Borderline personality disorder is characterized by mood instability, cognitive symptoms, impulsive behavior, and disturbed relationships (1-3). A variety of psychotherapies have been developed (4-6) and, while research on the use of medication is ongoing, no drug has been approved in the United States or elsewhere for its treatment (7). Second generation antipsychotics have been the most intensively studied (8-11). Current treatments for BPD are often inadequate. Dialectical behavioral therapy has been shown to reduce BPD but finding trained psychologists is difficult.

Dysfunctions in the serotoninergic and dopaminergic systems have been demonstrated in-and considered as possible causes for-symptoms associated with the disorder (25-28). Several studies on the use of traditional (29) and atypical antipsychotic agents in patients with borderline personality disorder (30-31) have shown a positive effect on individual symptoms (29, 32-36). However, we are not aware of any study evaluating Brexpiprazole in the treatment of patients with borderline personality disorder. In the proposed double-blind, placebo-controlled study, the influence of Brexpiprazole on the multifaceted psychopathological symptoms and aggression of patients with borderline personality disorder will be investigated.

Brexpiprazole therefore has distinctive properties that make it a promising option for patients with BPD. Brexpiprazole is a novel D2 partial agonist, has affinity for 5-HT1A, acts as an antagonist of the noradrenergic α1/2 receptor, partial agonist for D3, and antagonist for 5-HT2A (37-39). In addition, because of low rates of side effects, Brexpiprazole should be a well-tolerated and in fact desired medication approach to BPD.

Study Type

Interventional

Enrollment (Actual)

80

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Illinois
      • Chicago, Illinois, United States, 60637
        • University of Chicago

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 63 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  1. Men and women age 18-65;
  2. Primary diagnosis of BPD
  3. Zanarini scale score of at least 9 at baseline
  4. Ability to understand and sign the consent form.

Exclusion Criteria:

  1. Unstable medical illness based on history or clinically significant abnormalities on baseline physical examination
  2. Subjects with schizophrenia or bipolar I disorder
  3. Subjects with an active substance use disorder
  4. Current pregnancy or lactation, or inadequate contraception in women of childbearing potential
  5. Subjects considered an immediate suicide risk based on the Columbia Suicide Severity rating Scale (C-SSRS) (www.cssrs.columbia.edu/docs)
  6. Illegal substance use based on urine toxicology screening
  7. Initiation of psychological interventions within 3 months of screening
  8. Use of any other psychotropic medication
  9. Previous treatment with Brexpiprazole
  10. Cognitive impairment that interferes with the capacity to understand and self-administer medication or provide written informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: Placebo
1 milligram per day for the first week and 1 milligram per day for the final taper week 2 milligrams per day for 10 weeks between taper periods.
Drug: Placebo
Pill that contains no medicine
Other Names:
  • no other names
Experimental: Rexulti
1 milligram per day day for the first week and 1 milligram per day for the final taper week 2 milligrams per day for 10 weeks between taper periods.
Drug: Rexulti
Atypical antipsychotic
Other Names:
  • Brexpiprazole

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Zanarini Rating Scale for Borderline Personality Disorder
Time Frame: Baseline (Visit 1), Week 1 (Visit 2), Week 2 (Visit 3), Week 4 (Visit 4), Week 6 (Visit 5), Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8)
A clinician-administered scale assessing Borderline Personality Scale severity at all study visits. Scores range from 0-36. Higher scores represent worse Borderline Personality Disorder severity, and lower scores represent milder Borderline Personality Disorder severity.
Baseline (Visit 1), Week 1 (Visit 2), Week 2 (Visit 3), Week 4 (Visit 4), Week 6 (Visit 5), Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8)

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Modified Overt Aggression Scale (MOAS)
Time Frame: Baseline (Visit 1), Week 1 (Visit 2), Week 2 (Visit 3), Week 4 (Visit 4), Week 6 (Visit 5), Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8)
A clinician-administered behavior rating scale measuring four types of aggressive behavior that will be assessed at all 9 visits. The subsets range on a scale from 0-4 with 0 indicating no aggression present. This scale tracks changes in level of aggression over time. The total weighted sum of the sections of the scale is recorded. Higher total scores indicate higher aggression levels.
Baseline (Visit 1), Week 1 (Visit 2), Week 2 (Visit 3), Week 4 (Visit 4), Week 6 (Visit 5), Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8)
Young Mania Rating Scale
Time Frame: Baseline (Visit 1), Week 1 (Visit 2), Week 2 (Visit 3), Week 4 (Visit 4), Week 6 (Visit 5), Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8)
A clinician-administered, 11 item scale that assesses manic symptoms at baseline and over time. Higher total scores indicate higher severity of manic symptoms. This scale is used to rate the severity of manic abnormality in the patient. Subsets of the scale range from 0-4 with 0 indicating no severity. This scale will be assessed at all visits.
Baseline (Visit 1), Week 1 (Visit 2), Week 2 (Visit 3), Week 4 (Visit 4), Week 6 (Visit 5), Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8)
Self Report Version of Zanarini Scale
Time Frame: Baseline (Visit 1), Week 1 (Visit 2), Week 2 (Visit 3), Week 4 (Visit 4), Week 6 (Visit 5), Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8)
A self-report scale assessing Borderline Personality severity that will be assessed at all visits.This scale is assessing severity and change in BPD symptoms. This is a 9-item scale measuring severity of different aspects of Borderline Personality Disorder, with each item rated on a 0-4 scale, 0=no symptoms, 4=severe symptoms. Total scores range from 0-36.
Baseline (Visit 1), Week 1 (Visit 2), Week 2 (Visit 3), Week 4 (Visit 4), Week 6 (Visit 5), Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8)
Borderline Evaluation of Severity Over Time (BEST)
Time Frame: Assessed at Visits 1 to 8, change in scores from Visit 1 to Visit 8 (baseline to week 12) is reported
A self rated scale used to measure severity and change. The first 12 items of the scale are on a scale from 1-5, with 5 meaning that the item caused extreme distress, severe difficulties in relationships, and/or kept them from getting things done. The lowest rating (1) means it caused little or no problems. Items 13-15 (positive behaviors) are rated according to frequency. Completed at every visit.
Assessed at Visits 1 to 8, change in scores from Visit 1 to Visit 8 (baseline to week 12) is reported
Barratt Impulsiveness Scale (BIS)
Time Frame: Baseline (Visit 1), Week 12 (Visit 8)
A self-report assessment of impulsivity that will be assessed at baseline and visit 8. The BIS is composed of 30 items describing common impulsive or non-impulsive (for reverse scored items) behaviors and preferences. Items are scored on a 4-point scale: (Rarely/Never = 1, Occasionally = 2, Often = 3, Almost Always/Always = 4). These scores are summed to produce an overall impulsivity score ranging from 30 (not impulsive) to 120 (extremely impulsive).
Baseline (Visit 1), Week 12 (Visit 8)
Symptom Checklist-90 Revised
Time Frame: Baseline, Visit 8 (Week 12)
An instrument that helps evaluate a broad range of psychological problems and symptoms of Borderline Personality Disorder psychopathology. This will be assessed at baseline and visit 8.The 115 items are rated by using a 5-step Likert scale (0=not at all, 4=very strong) and provide a global picture of borderline psychopathology. Global scores of borderline psychopathology are calculated by summing 12 items and range from 0-48. Higher scores indicate more severe symptoms of Borderline Personality Disorder.
Baseline, Visit 8 (Week 12)
Hamilton Anxiety Rating Scale (HAM-A)
Time Frame: assessed at Visits 1 to 8, change in scores from Visit 1 to Visit 8 (baseline to Week 12) is reported
A clinician-administered assessment of anxiety that will be assessed at all study visits (Visit 1-Visit 8). Changes in scores from baseline to final visit will be assessed. Higher scores (up to 56) indicate higher levels of anxiety, with 0 being no symptoms of anxiety.
assessed at Visits 1 to 8, change in scores from Visit 1 to Visit 8 (baseline to Week 12) is reported
Hamilton Depression Rating Scale (HAM-D)
Time Frame: Assessed at Visits 1 to 8, change in scores from Visit 1 to Visit 8 (baseline to week 12) is reported
A clinician-administered assessment of depression that will be assessed at all study visits (Visits 1-8). Higher total scores indicate higher levels of depression (up to 52), while a score of 0 would indicate no depressive symptoms.
Assessed at Visits 1 to 8, change in scores from Visit 1 to Visit 8 (baseline to week 12) is reported
MINI International Neuropsychiatric Interview
Time Frame: Baseline (Week 1)
A short-structured interview that assesses comorbid psychiatric disorders according to the DSM 5 criteria. This assessment will be done during the baseline visit.
Baseline (Week 1)
Sheehan Disability Scale (SDS)
Time Frame: Baseline (Visit 1), Week 1 (Visit 2), Week 2 (Visit 3), Week 4 (Visit 4), Week 6 (Visit 5), Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8)
Subjects will complete the SDS at all visits. The change in scores from baseline to study completion will be assessed. The scale itself assesses the level of disability from borderline personality disorder (or target disorder) with higher scores indicating a more debilitating disorder. Scores range from 0-30.
Baseline (Visit 1), Week 1 (Visit 2), Week 2 (Visit 3), Week 4 (Visit 4), Week 6 (Visit 5), Week 8 (Visit 6), Week 10 (Visit 7), Week 12 (Visit 8)
Quality of Life Inventory (QOLI)
Time Frame: Baseline (Week 1), Week 12 (Visit 8)
A self-report assessment of patient perceived quality of life that will be assessed at baseline and visit 8. Higher scores indicate a higher quality of life, whereas lower scores indicate a lower quality of life. Participants are asked to rate the importance of each domain on a 3-point scale ranging from 1=not important to 3=very important, and to rate how satisfied they are with that domain on a 6-point scale, ranging from -3=very dissatisfied to +3=very satisfied. In scoring, importance ratings are multiplied by satisfaction ratings to produce weighted satisfaction scores for each of the 16 domains. Weighted satisfaction scores are summed and divided by the number of domains that were rated as important or very important to produce a raw score, which is then converted to a t-score, which provides a proxy measurement for perceived quality of life. T-scores range from very low perceived quality of life (0-36) to high perceived quality of life (58-77).
Baseline (Week 1), Week 12 (Visit 8)
Columbia Suicide Severity Rating Scale (CSSRS)
Time Frame: Baseline (Visit 1), Week 12 (Visit 8)
A self-report scale measuring suicidality. Subjects will complete the scale at all visits. Subjects are asked about suicidal thoughts. If answers are no, rater can proceed to "suicidal behavior" section where subject is asked about any non-suicidal self injurious behavior. If yes, subject is asked about intensity of ideations. In the event of serious threat to themselves, the subject will be escorted to the emergency room. Total score indicates severity of suicidal ideation and behavior, with lower scores representing lower levels of suicidality and higher scores representing higher levels of suicidality. A score of 0 would reflect no suicidality present, whereas a maximum score of 5 would reflect active suicidal ideation with intent to act.
Baseline (Visit 1), Week 12 (Visit 8)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Chicago

Collaborators

Otsuka America Pharmaceutical

Investigators

  • Principal Investigator: Jon E Grant, JD, MD, MPH, University of Chicago

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 26, 2018

Primary Completion (Actual)

December 30, 2020

Study Completion (Actual)

April 14, 2021

Study Registration Dates

First Submitted

January 25, 2018

First Submitted That Met QC Criteria

January 25, 2018

First Posted (Actual)

February 1, 2018

Study Record Updates

Last Update Posted (Actual)

March 18, 2022

Last Update Submitted That Met QC Criteria

March 16, 2022

Last Verified

March 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 17-1729

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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