RU-486 in the Treatment of Bipolar Depression

NCT ID: NCT00359125

Last Updated: 2014-01-22

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: PHASE2
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-07-31
• Study Completion Date: 2010-12-31

Brief Summary

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).

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.

Conditions

Bipolar Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

1

RU-486, 600 mg/day for 1 week.

Group Type: ACTIVE_COMPARATOR

mifepristone (RU-486)

Intervention Type: DRUG

RU-486, 600 mg/day for 1 week.

2

Placebo, 600 mg/day for 1 week

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: OTHER

Placebo, 600 mg/day for 1 week.

Interventions

mifepristone (RU-486)

RU-486, 600 mg/day for 1 week.

Intervention Type: DRUG

Placebo

Placebo, 600 mg/day for 1 week.

Intervention Type: OTHER

Other Intervention Names

Mifepristone

Eligibility Criteria

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.

• Minimum Eligible Age: 19 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Western Economic Diversification Canada

OTHER_GOV

Sponsor Role: collaborator

Stanley Medical Research Institute

OTHER

Sponsor Role: collaborator

University of British Columbia

OTHER

Sponsor Role: lead

Responsible Party

University of British Columbia

Principal Investigators

Allan Young, MD

Role: PRINCIPAL_INVESTIGATOR

The University of British Columbia

Locations

University of British Columbia, Dept. of Psychiatry

Vancouver, British Columbia, Canada

Countries

Canada

Other Identifiers

H06-0093

Identifier Type: -

Identifier Source: secondary_id

C06-0327

Identifier Type: -

Identifier Source: org_study_id

NCT00363064

Identifier Type: -

Identifier Source: nct_alias