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

This study is currently recruiting participants. (see Contacts and Locations)
Verified October 2014 by Indiana University
Sponsor:
Information provided by (Responsible Party):
Nikki Mehdiyoun, Indiana University
ClinicalTrials.gov Identifier:
NCT01212588
First received: September 29, 2010
Last updated: October 14, 2014
Last verified: October 2014
  Purpose

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.


Condition Intervention Phase
Borderline Personality Disorder
Drug: mifepristone
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Symptom reduction [ Time Frame: 7 days of study medication ] [ Designated as safety issue: No ]
    To determine if mifepristone is superior to placebo in symptom reduction (BPDSI total score)

  • Durable symptom improvement [ Time Frame: 21 days after discontinuation of study medication ] [ Designated as safety issue: No ]
    To determine if mifepristone is superior to placebo in symptom reduction (BPDSI total score)

  • Safety [ Time Frame: 7 days of study medication ] [ Designated as safety issue: Yes ]
    To determine safety of 600mg daily mifepristone according to laboratory assessments and electrocardiographs.

  • Tolerability [ Time Frame: 7 days of study medication ] [ Designated as safety issue: No ]
    To determine tolerability of 600 mg daily mifepristone according to subject report of adverse events

  • Biomarker of HPA-axis [ Time Frame: 21 days after discontinuation of study medication ] [ Designated as safety issue: No ]
    Cortisol laboratory levels


Secondary Outcome Measures:
  • Symptom reduction [ Time Frame: 7 days of study medication ] [ Designated as safety issue: No ]
    BPDSI symptom subscales scores

  • Symptom reduction [ Time Frame: 7 days of study medication ] [ Designated as safety issue: No ]
    BPRS scores

  • Symptom reduction [ Time Frame: 7 days of study medication ] [ Designated as safety issue: No ]
    SCL-90-R scores

  • Symptom reduction [ Time Frame: 7 days of study medication ] [ Designated as safety issue: No ]
    CGI-I score

  • Metacognitive capacity [ Time Frame: 21 days after discontinuation of study medication ] [ Designated as safety issue: No ]
    Indiana Psychiatric Illness Interview scores

  • Durable symptom improvement [ Time Frame: 21 days after discontinuation of study medication ] [ Designated as safety issue: No ]
    BPDSI symptom subscales scores

  • Durable symptom improvement [ Time Frame: 21 days after discontinuation of study medication ] [ Designated as safety issue: No ]
    BPRS total score


Estimated Enrollment: 24
Study Start Date: September 2010
Estimated Study Completion Date: March 2016
Estimated Primary Completion Date: September 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Mifepristone
Mifepristone 600mg once daily x 7 days
Drug: mifepristone
Mifepristone 600mg (3x200mg tablets) once daily for seven days
Placebo Comparator: Placebo
Matching placebo tablets one daily
Drug: Placebo
3 tablets once daily for seven days

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, 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 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

Ages Eligible for Study:   18 Years to 55 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 18-55 years of age at study entry
  • Female
  • 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:

    • CGI-S score of less than or equal to 5 (markedly ill) at randomization AND
    • 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 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 > 20 on the BPDSI
  • 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, 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
  • Steroid treatment of any sort (except topical, low dose hydrocortisone) within 4 weeks prior to randomization
  • Pregnant or lactating women or women who plan to become pregnant or will be lactating within one month after cessation of study medication
  • Known IQ <80 based on medical history
  • Currently using an intrauterine device (IUD)
  • 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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01212588

Contacts
Contact: Nikki Mehdiyoun, MA, CCRP 317-941-4287 iupdp@iupui.edu
Contact: Emily Good, MS 317-941-4287 iupdp@iupui.edu

Locations
United States, Indiana
Larue D Carter Memorial Hospital Recruiting
Indianapolis, Indiana, United States, 46222
Contact: Nikki Mehdiyoun, MA, CCRP    317-941-4287    iupdp@iupui.edu   
Contact: Emily Good, MS    317-941-4287    iupdp@iupui.edu   
Principal Investigator: Alan Breier, MD         
Sub-Investigator: Nikki Mehdiyoun, MA         
Sub-Investigator: Emily Good, MS         
Sub-Investigator: Amanda Roebel, MS         
Sub-Investigator: Alexander Radnovich, MD         
Sub-Investigator: Emily Liffick, MD         
Sub-Investigator: Michael Francis, MD         
Sub-Investigator: Megan Gaunnac, MBA         
Sub-Investigator: Steven M Lindgren, BA         
Sub-Investigator: Nawead Ayoubi         
Sub-Investigator: Kelsey Benson, BS         
Sub-Investigator: Jessica Bertram         
Sub-Investigator: Ching-Pin Chang, MD         
Sub-Investigator: Thomas Hummer, PhD         
Sub-Investigator: Lindsay Joy, BA         
Sub-Investigator: Richard Kovacs, MD         
Sub-Investigator: Bethany Leonhardt, PsyD         
Sub-Investigator: Frederick Malloy, MA         
Sub-Investigator: Ronald Mastouri, MD         
Sub-Investigator: Emmalee Metzler, BA         
Sub-Investigator: Joan Showalter, MA         
Sub-Investigator: David Spradley, RD         
Sub-Investigator: Marshayla Thompson         
Sub-Investigator: Amy Visco, BS         
Sub-Investigator: Jennifer Vohs, PhD         
Sub-Investigator: Angela Wallen         
Sub-Investigator: Dominique White, MS         
Sub-Investigator: Matthew Yung, BA         
Sub-Investigator: Hai Liu, PhD         
Sub-Investigator: Susan Perkins, PhD         
Sponsors and Collaborators
Indiana University
  More Information

Additional Information:
No publications provided

Responsible Party: Nikki Mehdiyoun, Clinical Research Manager, Indiana University
ClinicalTrials.gov Identifier: NCT01212588     History of Changes
Other Study ID Numbers: 1011002977
Study First Received: September 29, 2010
Last Updated: October 14, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Indiana University:
BPD
Borderline
personality disorder
mifepristone

Additional relevant MeSH terms:
Borderline Personality Disorder
Disease
Personality Disorders
Mental Disorders
Pathologic Processes
Glucocorticoids
Mifepristone
Abortifacient Agents
Abortifacient Agents, Steroidal
Contraceptive Agents
Contraceptive Agents, Female
Contraceptives, Oral
Contraceptives, Oral, Synthetic
Contraceptives, Postcoital
Contraceptives, Postcoital, Synthetic
Hormone Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Luteolytic Agents
Menstruation-Inducing Agents
Pharmacologic Actions
Physiological Effects of Drugs
Reproductive Control Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014