Borderline Personality Disorder
Conditions
Brief summary
The primary objective of the proposed study is to evaluate the safety and efficacy of Caplyta (lumateperone) in adults with borderline personality disorder (BPD). Sixty subjects with BPD will be randomized in a 1:1 fashion to either Caplyta (42mg/day) or matching placebo for 8 weeks of active treatment. The hypothesis to be tested is that Caplyta will result in greater rates of reduction in symptoms of BPD compared to placebo (improvement in symptoms will be indicated by lower scores on established outcome measures of BPD symptoms that have been used in prior studies).
Detailed description
Borderline personality disorder (BPD) is a serious, difficult to treat, psychiatric disorder that causes significant emotional distress, as well as resulting in significant economic burden to health care systems. A variety of psychotherapies, particularly dialectical behavior therapy (DBT) and systems training for emotional predictability and problem solving (STEPPS), have shown benefit in reducing many of the core symptoms of BPD. Healthcare systems, however, often lack the funding and appropriate expertise to implement these treatments, and finding trained DBT or STEPPS therapists has been difficult for many people with BPD. While research on the use of medication is ongoing, no drug has yet been approved in the United States or elsewhere for the treatment of BPD. Antidepressants, anti-convulsants, and second generation antipsychotics have all been examined, but current medication options for BPD often provide only partial relief and may have pronounced side effects. BPD is characterized by a pervasive pattern of severe psychopathological symptoms with instability of affect regulation, impulse control, and aggression. Dysfunctions in the serotoninergic, dopaminergic, and glutamatergic systems have been demonstrated in-and considered as possible causes for-symptoms associated with the disorder. Caplyta (lumateperone) therefore has distinctive properties that make it a promising option for patients with BPD. Caplyta is a mechanistically novel agent as it simultaneously modulates serotonin, dopamine, and glutamate, the key neurotransmitters implicated in BPD. Specifically, Caplyta acts as a potent serotonin 5-HT2A receptor antagonist, a dopamine D2 receptor pre-synaptic partial agonist and post-synaptic antagonist, a D1 receptor-dependent modulator of glutamate, and a serotonin reuptake inhibitor. In addition, because of low rates of side effects, Caplyta should be a well-tolerated and in fact desired medication approach to BPD. The aim of the present study is to examine the efficacy and safety of Caplyta vs. placebo in adults with BPD, as indicated by a score of at least 9 on the Zanarini Rating Scale for Borderline Personality Disorder ("Zanarini scale"), a scale of illness severity, at the baseline visit.
Interventions
DRUGPlacebo
Pill that contains no medicine.
DRUGCaplyta
Atypical antipsychotic
Sponsors
University of Chicago
Intra-Cellular Therapies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
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. Currently receiving for at least the last 2 months prior to study entry some form of weekly cognitive behavioral therapy 5. 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 (excluding marijuana given the high rates of marijuana use in BPD and the lack of interaction with Caplyta). 7. Use of any new psychotropic medication started within the last 3 months prior to study initiation 8. Previous treatment with Caplyta 9. Cognitive impairment that interferes with the capacity to understand and self-administer medication or provide written informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) Total Score | 8 weeks | The ZAN-BPD is a clinician-administered scale assessing borderline personality disorder symptom severity (total scores range from 0-36). Higher scores indicate more severe symptoms. The ZAN-BPD will be administered at all 5 visits, but only the change from baseline to visit 5 at week 8 will be reported. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Modified Overt Aggression Scale (MOAS) Total Score | 8 weeks | The MOAS is a clinician-administered behavior rating scale measuring four types of aggressive behavior. The MOAS will be administered at all 5 visits, but only the change from baseline to visit 5 at week 8 will be reported. The total weighted scores range from 0-40, with 0 indicating no aggression. Higher total scores indicate higher aggression levels. |
| Change in Young Mania Rating Scale (YMRS) Total Score | 8 weeks | The YMRS is a clinician-administered, 11-item scale assessing manic symptoms at baseline and over time. The YMRS will be administered at all 5 visits, but only the change from baseline to visit 5 at week 8 will be reported. Higher total scores (ranging from 0-60) indicate higher severity of manic symptoms. This scale is used to rate the severity of manic abnormality in participants. |
| Change in Zanarini Rating Scale for Borderline Personality Disorder Self-Report Version (ZAN-BPD-SRV) Total Score | 8 weeks | The ZAN-BPD-SRV is a self-report scale assessing borderline personality severity that will be assessed at all 5 visits. However, only the change from baseline to visit 5 at week 8 will be reported. Scoring is done by counting the number of yes's. Total scores range from 0-36, with higher scores indicating more severe symptoms. A score of 8 or more is indicative of a diagnosis of borderline personality disorder. |
| Change in Borderline Evaluation of Severity Over Time (BEST) Total Score | 8 weeks | The BEST is a self-rated scale used to measure severity and change. The first 12 items of the scale are scored on a scale from 1-5, with 5 meaning that the item caused extreme distress, severe difficulties in relationships, and/or kept the participant 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. Items 13-15 are rated 1-5 with 5 indicating more frequent symptoms. The scale ranges from 12-72 with higher scores indicating more severe symptoms. The score for items 1-12 are added together, the score from items 13-15 are then subtracted, and then 15 is added to obtain the total score. The BEST will be administered at all 5 visits, but only the change from baseline to visit 5 at week 8 will be reported. |
| Change in Barratt Impulsiveness Scale (BIS-11) Total Score | 8 weeks | This BIS-11 is a self-report assessment of impulsivity that will be assessed at baseline and Visit 5. The change from baseline to visit 5 at week 8 will be reported. All items are added to result in a total score ranging from 30-120. Higher total scores indicate higher impulsiveness. |
| Minnesota Impulsive Disorders Interview (MIDI) | Baseline | The MIDI is a clinical interview that screens for a variety of impulsive disorders, including buying disorder, kleptomania, trichotillomania, intermittent explosive disorder, pyromania, gambling disorder, compulsive sexual behavior, binge eating disorder, and compulsive exercise. The results of the MIDI at baseline will be reported. |
| Change in Hamilton Depression Rating Scale (HAM-D) Total Score | 8 weeks | The HAM-D is a clinician-administered assessment of depression that will be assessed at all 5 study visits. However, only the change from baseline to visit 5 at week 8 will be reported. Higher total scores (ranging from 0-52) indicate higher levels of depression, while a score of 0 would indicate no depressive symptoms. |
| Change in Hamilton Anxiety Rating Scale (HAM-A) Total Score | 8 weeks | The HAM-A is a clinician-administered assessment of anxiety that will be assessed at all 5 study visits. However, only the change from baseline to visit 5 at week 8 will be reported. Higher total scores (ranging from 0-56) indicate higher levels of anxiety, with 0 being no symptoms of anxiety. |
| Change in Quality of Life Inventory (QOLI) Total Weighted Satisfaction Score | 8 weeks | The QOLI is a self-report assessment of patient perceived quality of life that will be assessed at baseline and visit 5. The change in total weighted satisfaction scores from baseline to visit 5 at week 8 will be reported. Higher scores (ranging from -96 to 96) indicate a higher quality of life, whereas lower scores indicate a lower quality of life. |
| Change in Sheehan Disability Scale (SDS) Total Score | 8 weeks | Subjects will complete the SDS at all 5 visits. The change in total scores (ranging from 0-30) from baseline to visit 5 at week 8 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORJon E Grant, MD, JD, MPH
University of Chicago
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Continuous | 32.03 Years STANDARD_DEVIATION 11.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 3 Participants |
| Race (NIH/OMB) Black or African American | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) White | 31 Participants |
| Sex/Gender, Customized Sex Female | 41 Participants |
| Sex/Gender, Customized Sex Male | 12 Participants |
| Sex/Gender, Customized Sex Other | 2 Participants |
| Zanarini Rating Scale for Borderline Personality Disorder (ZAN-BPD) Total Score | 14.84 Units on a scale STANDARD_DEVIATION 3.3 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 31 | 0 / 29 |
| other Total, other adverse events | 16 / 31 | 14 / 29 |
| serious Total, serious adverse events | 1 / 31 | 0 / 29 |
Outcome results
None listed