Clinical trial NCT01212588: Preliminary Trial of the Effect of Glucocorticoid Receptor Antagonist on Borderline Personality Disorder (BPD)
Official title: Preliminary, Double Blind, Placebo Controlled Trial of the Effect of Glucocorticoid Receptor Antagonist Treatment on Biologic and Symptom Outcomes in Patients With Borderline Personality Disorder and Histories of Childhood Abuse
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Borderline Personality Disorder
Keywords: BPD
Borderline
personality disorder
mifepristone
Lead sponsor: Indiana University
Sponsor class: OTHER
First posted: 2010-09-30
Enrollment: 22
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed description: Mifepristone is an antagonist of type II glucocorticoid (GR-II) receptors, which has shown safety, efficacy, and good tolerability in the treatment of psychotic major depression (PMD). Like BPD, Hypothalamic-pituitary-adrenal (HPA) axis hyper-responsiveness appears to play a role in PMD pathophysiology. Belanoff et al. (2002) hypothesized that mifepristone causes a normalizing "resetting" of HPA axis rhythm, accounting for its efficacy in PMD. Mifepristone produces a marked (2- to 3- fold) compensatory increase in central cortisol levels via its antagonism of GR-II receptors. This consequent central cortisol elevation may then be able to counteract abnormally heightened corticotrophin-releasing hormone (CRH) activity via enhanced negative feedback mechanisms.

This is a proof of principle study of mifepristone in the treatment of individuals with BPD and histories of childhood abuse, which aims to translate neurobiological research concerning HPA axis abnormalities in BPD into a novel clinical intervention for patients. This project will also explore an innovative approach to the structure of pharmacotherapy for BPD. Specifically, we will employ the circumscribed (finite) drug administration period used in prior studies of mifepristone in neuropsychiatric illness, which differs from the current clinical practice of indefinite daily usage of medications. We hypothesize that mifepristone will beneficially impact stress response neurobiology and consequently ameliorate associated BPD symptoms.

Eligibility criteria: Inclusion Criteria:

* 18-64 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

Exclusion Criteria:

* 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
* Use of any exclusionary medications listed in the protocol Attachment 2: Concomitant Medications
* 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
* History of unexplained vaginal bleeding, endometrial hyperplasia with atypia, or endometrial carcinoma

Primary outcomes:
measure: Rapid Symptom Change
timeFrame: Baseline to 7 days of study medication
measure: Durable Symptom Change
timeFrame: 7 days of study medication to 21 days after discontinuation of study medication
measure: Number of Participants With Possibly and Probably Related Adverse Events
timeFrame: Baseline to 21 days after discontinuation of study medication
measure: Levels of Cortisol
timeFrame: 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:
measure: Symptom Change - BPDSI Subscales
timeFrame: Baseline (Visit 2)
measure: Symptom Change - BPRS
timeFrame: 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)
measure: Symptom Change - Borderline Checklist
timeFrame: 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)
measure: Symptom Change - SCL-90-R
timeFrame: Baseline (Visit 2)
measure: Metacognitive Capacity
timeFrame: Baseline, 21 days after discontinuation of study medication
measure: Symptom Change - CGI-S
timeFrame: Baseline, 7 days of study medication (Visit 4), 21 days after discontinuation of study medication (Visit 6)
measure: Symptom Change - CGI-I
timeFrame: 7 days of study medication (Visit 4), 21 days after discontinuation of study medication (Visit 6)
measure: Symptom Change - BPDSI Subscales
timeFrame: 7 days of study medication (Visit 4)
measure: Symptom Change - BPDSI Subscales
timeFrame: 21 days after discontinuation of study medication (Visit 6)
measure: Symptom Change - SCL-90-R
timeFrame: 7 days of study medication (Visit 4)
measure: Symptom Change - SCL-90-R
timeFrame: 21 days after discontinuation of study medication (Visit 6)
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Larue D Carter Memorial Hospital
state: Indiana
Study officials:
References: