RU-486 in the Treatment of Bipolar Depression

January 21, 2014 updated by: University of British Columbia

Efficacy of Mifepristone (RU-486) in the Treatment of Bipolar Depression.

Bipolar disorder is a chronic and recurrent illness which involves episodes of mania and depression. It is believed that disturbance of the stress hormone system (the hypothalamic-pituitary-adrenal or HPA axis) may cause thinking and memory problems and make the depressive symptoms worse in bipolar disorder. Early studies have shown that mifepristone may have antidepressant effects (may improve the symptoms of depression) and may also maintain or enhance cognition (memory and thinking functions).

The purpose of this study is to determine the potential therapeutic efficacy (usefulness) of mifepristone in bipolar depression by assessing the effects of the medication on depressive symptoms and on cognition. This will be done by questionnaires and thinking tests.

This study will also try to clarify the functional changes that accompany bipolar disorder by analyzing saliva samples (assessing the stress response by measuring the levels of 2 stress hormones: cortisol and DHEA).

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

Detailed Description

Detailed Description:

This study will be a parallel design randomized control trial. Duration of study is 10 weeks per subject. Following a baseline assessment of neurocognitive performance, mood symptoms, and neuroendocrine functioning (HPA axis functioning), bipolar depressed outpatients (n=100) will be randomized (week 0) to receive either mifepristone 600 mg daily (n=50) or matching placebo (n=50) for 7 days. Outcome measures will be completed at baseline (pre-medication), at the time of anticipated main response (week 3, i.e. 2 weeks after cessation of treatment), and at week 8 (to determine the persistence of any effects).

Neurocognitive performance (pre and post mifepristone treatment) will be evaluated with tests that have previously been shown to be affected by corticosteroids and to be abnormal in bipolar disorder. The neurocognitive battery will measure learning and memory, attention, executive functioning, and facial expression (which has been shown to be a sensitive measure of affective shift).

Mood symptoms will be evaluated at every study visit using standard clinician and patient self-rated scales.

Neuroendocrine functioning (HPA axis functioning) will be measured by the dexamethasone suppression test (DST) response to dexamethasone. This is a measure of the function of the glucocorticoid receptor. Subjects will also be asked for salivary samples to measure the cortisol response to wakening and the ratio of cortisol to the protective steroid DHEA. These validated tests will be used to improve our understanding of the mechanism of the therapeutic effect of mifepristone.

Fifty (50) matched-healthy controls will also undergo the baseline assessments of neurocognitive performance, mood symptoms, and neuroendocrine functioning. They will provide information about the pathophysiology of bipolar disorder.

Study Type

Interventional

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • British Columbia
      • Vancouver, British Columbia, Canada, V6T 1Z3
        • University of British Columbia, Dept. of Psychiatry

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 65 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

Inclusion Criteria:

Male & female outpatients between 19-65 years of age with a diagnosis of bipolar depression. Women must not be currently pregnant and must use a reliable method of contraception for the duration of the study. Subjects must be on stable medication (4 weeks minimum) for their bipolar illness. Subjects must be able to provide written informed consent. Subjects must adequately understand written & verbal English as rating scales as neurocognitive tests are only in English.

Exclusion Criteria:

Those not meeting the above criteria and those not competent to give informed consent. Women who are currently pregnant. Also excluded: those who have a clinically significant medical illness (including significant head injury with loss of consciousness), those at immediate risk of harming self or others, are currently abusing alcohol or drugs, those with a neurological disorder or uncompensated endocrine disorder, those with a known allergy to mifepristone, those currently being treated with an investigational medication or medication that is contraindicated with mifepristone.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1
RU-486, 600 mg/day for 1 week.
Drug: mifepristone (RU-486)
RU-486, 600 mg/day for 1 week.
Other Names:
  • Mifepristone
Placebo Comparator: 2
Placebo, 600 mg/day for 1 week
Other: Placebo
Placebo, 600 mg/day for 1 week.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Neurocognitive performance at weeks -1, 3 & 8 and symptom change at weeks -2, -1, 0, 1, 2, 3, 4, 5 & 8

Secondary Outcome Measures

Outcome Measure
HPA axis functioning from saliva samples at weeks -2, -1, 2, 3 & 8

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of British Columbia

Collaborators

Stanley Medical Research Institute
Western Economic Diversification Canada

Investigators

  • Principal Investigator: Allan Young, MD, The University of British Columbia

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2006

Primary Completion (Anticipated)

December 1, 2010

Study Completion (Anticipated)

December 1, 2010

Study Registration Dates

First Submitted

July 28, 2006

First Submitted That Met QC Criteria

July 28, 2006

First Posted (Estimate)

August 1, 2006

Study Record Updates

Last Update Posted (Estimate)

January 22, 2014

Last Update Submitted That Met QC Criteria

January 21, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • C06-0327
  • H06-0093

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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