Preliminary Trial of the Effect of Glucocorticoid Receptor Antagonist on Borderline Personality Disorder (BPD)

NCT01212588 | Terminated Phase 2 Results DMC

• 1 other identifier: 1011002977
• Study Type: interventional
• Target: 22
• Locations: 1 country
• Sites: 1

Brief Summary

Participants will be randomized to either Mifepristone 600mg once daily for seven days or Placebo tablet once daily for seven days. Rating scales, vital signs, cortisol levels will be collected for evaluation.

Conditions

Borderline Personality Disorder

Keywords

BPD; Borderline; personality disorder; mifepristone

Outcome Measures

Primary Outcomes (4)

• Rapid Symptom Change

  To evaluate whether mifepristone will produce rapid symptom change after seven days of active treatment, as measured by Borderline Personality Disorder Severity Index (BPDSI) total score. The BPDSI is a semi-structured clinical interview assessing the frequency and severity of manifestations of Borderline Personality Disorder (BPD) during a circumscribed period of the previous 7 days. The BPDSI measures 9 symptoms associated with BPD on a Likert scale ranging from 0-7 (0 = never; 7 = daily). Each symptom measure produces a mean score ranging from 0-7, with a higher score indicating more prevalent symptoms. A total score is then calculated using the summed symptom mean scores, ranging from 0-63, with a higher score indicating more prevalent symptoms.

  Baseline to 7 days of study medication

• Durable Symptom Change

  To evaluate whether seven days of mifepristone treatment will result in a durable change in symptoms persisting after active treatment discontinuation, as measured by Borderline Personality Disorder Severity Index (BPDSI) total score. The BPDSI is a semi-structured clinical interview assessing the frequency and severity of manifestations of Borderline Personality Disorder (BPD) during a circumscribed period of the previous 7 days. The BPDSI measures 9 symptoms associated with BPD on a Likert scale ranging from 0-7 (0 = never; 7 = daily). Each symptom measure produces a mean score ranging from 0-7, with a higher score indicating more prevalent symptoms. A total score is then calculated using the summed symptom mean scores, ranging from 0-63, with a higher score indicating more prevalent symptoms.

  7 days of study medication to 21 days after discontinuation of study medication

• Number of Participants With Possibly and Probably Related Adverse Events

  To determine the safety and tolerability of mifepristone according to subject report of possibly and probably related adverse events (AEs). AEs were evaluated by study physicians at each visit and each reported AE was evaluated for relatedness (unrelated, possibly related, or probably related) to the study drug/procedure.

  Baseline to 21 days after discontinuation of study medication

• Levels of Cortisol

  To assess cortisol levels as a potential biomarker of hypothalamic-pituitary-adrenal (HPA)-axis engagement

  Baseline (Visit 2), 7 days of study medication (Visit 4), 7 days after discontinuation of study medication (Visit 5), 21 days after discontinuation of study medication (Visit 6)

Secondary Outcomes (11)

• Symptom Change - BPDSI Subscales

  Baseline (Visit 2)

• Symptom Change - BPRS

  Baseline (Visit 2), 7 days of study medication (Visit 4), 7 days after discontinuation of study medication (Visit 5), 21 days after discontinuation of study medication (Visit 6)

• Symptom Change - Borderline Checklist

  Baseline (Visit 2), 7 days of study medication (Visit 4), 7 days after discontinuation of study medication (Visit 5), 21 days after discontinuation of study medication (Visit 6)

• Symptom Change - SCL-90-R

  Baseline (Visit 2)

• Metacognitive Capacity

  Baseline, 21 days after discontinuation of study medication

Study Arms (2)

Mifepristone

EXPERIMENTAL

Mifepristone 600mg once daily x 7 days

Drug: mifepristone

Placebo

PLACEBO COMPARATOR

Matching placebo tablets one daily

Drug: Placebo

Interventions

mifepristone DRUG

Mifepristone 600mg (3x200mg tablets) once daily for seven days

Mifepristone

Placebo DRUG

3 tablets once daily for seven days

Placebo

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• years of age at study entry
• Female or Male
• Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) diagnosis of borderline personality disorder (confirmed by SCID II) with history of abuse prior to the age of 18.
• Able to provide informed consent
• Inpatient or outpatient
• Clinical stability as defined by:
• Subjects must not have experienced an exacerbation of their illness within 4 weeks prior to randomization, leading to an intensification of psychiatric care in the opinion of the principal investigator. Examples of intensification of care include, but are not limited to: inpatient hospitalization, day/partial hospitalization, outpatient crisis management, or psychiatric treatment in an emergency room AND
• Psychotropic treatment stability for at least 2 weeks prior to randomization (no change in dosing or addition of any new psychotropic medication)
• Female subjects of childbearing potential must test negative for pregnancy at screening visit and agree to use the double-barrier method, as defined by 2 physical barriers such as a condom, diaphragm, or cervical occlusive cap, coupled with an additional barrier such as spermicidal foam, gel, film, cream or suppository for the duration of the study. Subjects having undergone a hysterectomy or bilateral oophorectomy or other form of female sterilization or patients having been medically confirmed to be post-menopausal, would not require any other method of contraception.
• Minimum severity of a total score \> 3 on the The Clinical Global Impression severity (CGI-S)
• Must agree not to consume tonic water and grapefruit or grapefruit product for 3 days prior to beginning medication and until the final study visit

You may not qualify if:

• DSM-IV TR diagnosis of (confirmed by SCID) schizophrenia or a related psychotic disorder, bipolar I disorder, or dementia
• Subjects who are considered prisoners per the Indiana University Standard Operating Procedures for Research Involving Human Subjects.
• Subjects with current acute, serious, or unstable medical conditions, including, but not limited to: inadequately controlled diabetes, asthma, Chronic obstructive pulmonary disease (COPD), severe hypertriglyceridemia, recent cerebrovascular accidents, acute systemic infection or immunologic disease, unstable cardiovascular disorders, malnutrition, renal gastroenterologic, respiratory, endocrinologic (particularly illnesses related to the HPA-axis, e.g., Cushing's Syndrome), neurologic, hematologic, or infectious diseases
• Clinically significant electrocardiogram (ECG) abnormality prior to randomization including: subjects with a corrected QT interval (Bazett's; QTcB) \>470 msec prior to randomization (based on the cardiologist overread). Repeat ECGs will be conducted at the discretion of the principal investigator or medical designee
• Pregnant or lactating women or women who plan to become pregnant or will be lactating within one month after cessation of study medication
• Known Intelligence quotient (IQ) \<70 based on medical history
• Currently using an intrauterine device (IUD) (females only)
• History of treatment with mifepristone or any mifepristone-containing medication at any time
• Known history of (1) Hepatitis C virus antibody, (2) Hepatitis B surface antigen (HBsAg) with or without positive Hepatitis B core total antibody, or (3) HIV 1 or 2 antibodies
• Subjects with moderate to severe renal impairment as defined by creatinine clearance (CrCl) \< 60 ml/min (measured by the Cockcroft-Gault equation) at screening
• Subjects with hepatic impairment as defined by liver transaminases or total bilirubin \> 3 × upper limit of normal (ULN)
• Subjects considered a high risk for suicidal acts, as determined by the principal investigator.
• Subjects who have participated in a clinical trial with any pharmacological treatment intervention for which they received study-related medication in the 4 weeks prior to screening OR Subjects currently receiving treatment (within 1 dosing interval plus 4 weeks) with an investigational depot formulation of an antipsychotic medication
• Subjects who demonstrate overtly aggressive behavior or who are deemed to pose a homicidal risk in the principal investigator's opinion
• Psychosocial treatment changes 14 days prior to randomization

Sponsors & Collaborators

• Indiana University: lead

Study Sites (1)

Larue D Carter Memorial Hospital

Indianapolis, Indiana, 46222, United States

Location

MeSH Terms

Conditions

Borderline Personality Disorder; Personality Disorders

Interventions

Mifepristone

Condition Hierarchy (Ancestors)

Mental Disorders

Intervention Hierarchy (Ancestors)

Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Results Point of Contact

• Title: Dr. Alan Breier
• Organization: IndianaU

abreier@iupui.edu

317-880-8495

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Psychiatrist

Study Record Dates

• First Submitted: September 29, 2010
• First Posted: September 30, 2010
• Study Start: September 1, 2010
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: February 26, 2019
• Results First Posted: February 26, 2019

Record last verified: 2019-02

Locations

US (1)