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

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

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 Per

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 Summary:

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.


Sponsor: Indiana University

Current Primary Outcome:

  • Rapid symptom reduction [ Time Frame: 7 days of study medication ]
    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 ]
    To determine if mifepristone is superior to placebo in symptom reduction (BPDSI total score)
  • Safety [ Time Frame: 7 days of study medication ]
    To determine safety of 600mg daily mifepristone according to laboratory assessments and electrocardiographs.
  • Tolerability [ Time Frame: 7 days of study medication ]
    To determine tolerability of 600 mg daily mifepristone according to subject report of adverse events
  • Biomarker of HPA-axis [ Time Frame: 7 days of study medication ]
    Cortisol laboratory levels
  • Biomarker of HPA-axis [ Time Frame: 7 days after discontinuation of study medication ]
    Cortisol laboratory levels
  • Biomarker of HPA-axis [ Time Frame: 21 days after discontinuation of study medication ]
    Cortisol laboratory levels


Original Primary Outcome: Symptom reduction [ Time Frame: 28 days ]

as per study assessments


Current Secondary Outcome:

  • Rapid Symptom reduction [ Time Frame: 7 days of study medication ]
    BPDSI symptom domain subscales scores
  • Durable symptom improvement [ Time Frame: 21 days after discontinuation of study medication ]
    BPDSI symptom domain subscales scores
  • Rapid symptom reduction [ Time Frame: 7 days of study medication ]
    Brief Psychiatric Rating Scale (BPRS) score
  • Durable symptom improvement [ Time Frame: 21 days after discontinuation of study medication ]
    Brief Psychiatric Rating Scale (BPRS) score
  • Rapid symptom reduction [ Time Frame: 7 days of study medication ]
    Borderline Checklist Score
  • Durable symptom improvement [ Time Frame: 21 days after discontinuation of study medication ]
    Borderline Checklist Score
  • Rapid symptom reduction [ Time Frame: 7 days of study medication ]
    Symptom Checklist-90-Revised (SCL-90-R) Scores
  • Durable symptom improvement [ Time Frame: 21 days after discontinuation of study medication ]
    Symptom Checklist-90-Revised (SCL-90-R) Scores
  • Metacognitive Capacity [ Time Frame: 21 days after discontinuation of study medication ]
    Indiana Psychiatric Illness Interview (IPII) Scores
  • Rapid symptom reduction [ Time Frame: 7 days of study medication ]
    Clinical Global Impressions Severity (CGI-S) score
  • Durable symptom improvement [ Time Frame: 21 days after discontinuation of study medication ]
    Clinical Global Impressions Severity (CGI-S) score
  • Rapid symptom reduction [ Time Frame: 7 days of study medication ]
    Clinical Global Impressions Improvement (CGI-I) score
  • Durable symptom improvement [ Time Frame: 21 days after discontinuation of study medication ]
    Clinical Global Impressions Improvement (CGI-I) score


Original Secondary Outcome:

Information By: Indiana University

Dates:
Date Received: September 29, 2010
Date Started: September 2010
Date Completion: December 2017
Last Updated: January 30, 2017
Last Verified: January 2017