Clinical trial NCT03418675: Brexpiprazole in Borderline Personality Disorder
Official title: A Double-Blind, Placebo-Controlled Study of Brexpiprazole in the Treatment of Borderline Personality Disorder.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Borderline Personality Disorder
Lead sponsor: University of Chicago
Sponsor class: OTHER
Collaborators: name: Otsuka America Pharmaceutical
First posted: 2018-02-01
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Zanarini Rating Scale for Borderline Personality Disorder
timeFrame: 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 outcomes:
measure: Modified Overt Aggression Scale (MOAS)
timeFrame: 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)
measure: Young Mania Rating Scale
timeFrame: 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)
measure: Self Report Version of Zanarini Scale
timeFrame: 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)
measure: Borderline Evaluation of Severity Over Time (BEST)
timeFrame: Assessed at Visits 1 to 8, change in scores from Visit 1 to Visit 8 (baseline to week 12) is reported
measure: Barratt Impulsiveness Scale (BIS)
timeFrame: Baseline (Visit 1), Week 12 (Visit 8)
measure: Symptom Checklist-90 Revised
timeFrame: Baseline, Visit 8 (Week 12)
measure: Hamilton Anxiety Rating Scale (HAM-A)
timeFrame: assessed at Visits 1 to 8, change in scores from Visit 1 to Visit 8 (baseline to Week 12) is reported
measure: Hamilton Depression Rating Scale (HAM-D)
timeFrame: Assessed at Visits 1 to 8, change in scores from Visit 1 to Visit 8 (baseline to week 12) is reported
measure: MINI International Neuropsychiatric Interview
timeFrame: Baseline (Week 1)
measure: Sheehan Disability Scale (SDS)
timeFrame: 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)
measure: Quality of Life Inventory (QOLI)
timeFrame: Baseline (Week 1), Week 12 (Visit 8)
measure: Columbia Suicide Severity Rating Scale (CSSRS)
timeFrame: Baseline (Visit 1), Week 12 (Visit 8)
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Chicago
state: Illinois
Study officials:
affiliation: University of Chicago
name: Jon E Grant, JD, MD, MPH
role: PRINCIPAL_INVESTIGATOR
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