Bipolar DisorderPhase 2NCT00043654
Clinical Trial of Mifepristone for Bipolar Depression
A Phase 2 study testing Mifepristone in people with Bipolar Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
Trial summary
Bipolar Depression is a severe illness with high rates of psychiatric comorbidity and increased mortality related to suicide and medical illness. Hypothalamic pituitary axis (HPA) hyperactivity are found in bipolar disorder related to depression and mixed states. Read more about this study
- Who is it for?
- Ages 18 to 75 yearsHealthy volunteers can take part
- Conditions the study is for
- Bipolar Disorder
- What is being tested?
- Mifepristone
- How many people
- 110 participants
- Where
- 1 siteUnited States
- Study dates
- 7 Aug 2002to 25 Jun 2007
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients must meet the following inclusion criteria in order to participate in the study:
- Male or female inpatients in need of treatment for severe bipolar depression.
- 18-75 years of age.
- Women of childbearing potential must be using an adequate form of contraception as defined by one of the following: 1) a barrier method and 2) oral contraceptives plus a barrier method (women who are on an OCP will be kept on it others must agree to use only a barrier method).
- DSM-IV diagnosis of bipolar depression I/II, severe, with or without psychotic features.
- A current major depressive episode of at least 6 weeks' duration.
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- Score of greater than or equal to 18 on the first 17-item HAM-D at the prestudy visit and at the first baseline phase visit.
- Score of 15 or greater on the HAM-D (17) at the end of the baseline period(s) (i.e., at randomization no more than 20% less than entry enrollment criteria).
- Score of greater than or equal to 4 on the CGI-BP scale at the prestudy and first visit and end of baseline phase.
- Judged to be in good physical health on the basis of medical history, physical examination, and laboratory screening.
- Able to understand procedures and agree to participate in the study by giving written informed consent.
- On lithium and/or valproate for at least 4 weeks (2 levels, 1 wk apart)
- However patients not on a mood stabilizer can have this started as an outpatient or inpatient for 4 weeks as discussed above.
- Able to come off of prior drugs and PRN zolpidem and lorazepam by start of baseline.
- SCID-NP- no psychiatric diagnosis lifetime.
- Ages 18-75.
- Medically and psychiatrically healthy by history and no disallowed medications for 2 weeks, and agrees to no alcohol use for 1 week baseline period of study.
- No history of mood or anxiety disorder in first-degree relatives.
- Women of childbearing potential must be using adequate form of contraception as defined by one of the following: 1) a barrier method and 2) oral contraceptives plus a barrier method.
Who cannot join
- Patients will be excluded from the study if they meet any of the following criteria:
- Women who are pregnant, intending to become pregnant in the next month or breast-feeding.
- Treatment with any of the following therapies within the specified interval prior to baseline: Fluoxetine - 4 weeks; Investigational compounds 4 weeks; MAOIs 1 week; Other antidepressants 1 week.
- Contraindication or history of hypersensitivity to mifepristone as well as cortisol, and CRH.
- Clinically significant organ system disease where mifepristone would be contraindicated or interfere with medical treatment.
- Have evidence of any disorder that represents a contraindication to the use of mifepristone (such as adrenal disease or a condition requiring chronic corticosteroid administration).
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- History of Addison's Disease, Cushing's Disease, insulin dependent diabetes, or other uncompensated endocrine conditions.
- Evidence of infection, severe liver, respiratory, or renal disease.
- Have clinically significant cardiovascular disease, e.g., angina, valve disease, arrhythmia, cardiac failure.
- Anemia (hemoglobin less than 10 g/dL or hematocrit less than 30%)
- Have a known clotting defect or are receiving anticoagulants.
- Rapid cycling in the last year (defined as greater than 6 episodes).
- History of porphyrias.
- Clinically significant abnormalities in physical exam, ECG, or laboratory assessments.
- History of any disease which, in the investigator's opinion may confound the results of the study or pose an additional risk, including but not limited to, history of organic mental disorder, seizures, or mental retardation.
- Substance dependence that is not in sustained full remission (DSM-IV definition)
- Other principal psychiatric diagnosis judged by the investigator to dominate the clinical presentation. In particular, patients with depressive symptoms more than 2 years in duration should be carefully evaluated to determine whether another psychiatric diagnosis exists which could interfere with efficacy and safety measurements.
- History of nonresponse to greater than four trials of antidepressants for the current episode (not including mood stabilizers) will exclude subjects.
- Known hypersensitivity to CRH, hydrocortisone, metyrapone, or mifepristone.
- Women who are pregnant or breast-feeding.
- Clinically significant organ system disease where mifepristone would be contraindicated or interfere with medical treatment.
- History of prophyrias.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104-6056
About this study
Official title: Antiglucocorticoid Therapy in Bipolar Depression With Mifepristone (RU486)
Bipolar Depression is a severe illness with high rates of psychiatric comorbidity and increased mortality related to suicide and medical illness. Hypothalamic pituitary axis (HPA) hyperactivity are found in bipolar disorder related to depression and mixed states. Patients with bipolar disorder also have cognitive difficulties and endocrine disturbances may contribute to such dysfunction. Antiglucorticoid therapies are novel treatments of mood disorder. Preliminary data in psychotic depression suggesting that mifepristone (RU-486), a glucocorticoid receptor antagonist, has antidepressant and salutary cognitive effects in a matter of days. In this study we examine the effects of mifepristone in severe bipolar depression in a parallel, double blind placebo controlled experiment. Bipolar subjects maintained on either lithium or valproate, after washout or prior antidepressants have a detailed neuroendocrine assessment. Patients approximately or almost 75 will receive eight days of mifepristone versus placebo after which patients are blindly crossed over to the opposite arm. Patients and a group of matched controls approximately or almost 35 will be compared with neuroendocrine, cognitive, and neurophysiologic testing to fully characterize their phenotype and explore biomarkers of response. It is hypothesized that stigmata of HPA axis hyperactivity and cognitive impairment will be predictive of response to antiglucocorticoid therapy with mifepristone.
Read the detailed description
Bipolar Depression is a severe illness with high rates of psychiatric comorbidity and increased mortality related to suicide and medical illness. Hypothalamic pituitary axis (HPA) hyperactivity are found in bipolar disorder related to depression and mixed states. Patients with bipolar disorder also have cognitive difficulties and endocrine disturbances may contribute to such dysfunction. Antiglucorticoid therapies are novel treatments of mood disorder. Preliminary data in psychotic depression suggesting that mifepristone (RU-486), a glucocorticoid receptor antagonist, has antidepressant and salutary cognitive effects in a matter of days. In this study we examine the effects of mifepristone in severe bipolar depression in a parallel, double blind placebo controlled experiment. Bipolar subjects maintained on either lithium or valproate, after washout or prior antidepressants have a detailed neuroendocrine assessment. Patients approximately or almost 75 will receive eight days of mifepristone versus placebo after which patients are blindly crossed over to the opposite arm. Patients and a group of matched controls approximately or almost 35 will be compared with neuroendocrine, cognitive, and neurophysiologic testing to fully characterize their phenotype and explore biomarkers of response. It is hypothesized that stigmata of HPA axis hyperactivity and cognitive impairment will be predictive of response to antiglucocorticoid therapy with mifepristone.
- Conditions
- Bipolar Disorder
- Being tested
- Mifepristone
- Keywords
- Antidepressant, Manic-Depressive Disorder, Cortisol, Neuroendocrine, Cognition, Bipolar, Bipolar Disorder, BPD, HV
- Medical subject headings
- Bipolar Disorder
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MifepristoneDrug
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Aug 2002 (estimated)
- Study start7 Aug 2002
- Study completion25 Jun 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Bipolar DisorderStudies of the same condition, open and under way.
- More trials run by National Institute of Mental Health (NIMH)The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Enrolment
- 110 participants
Sponsor and investigators
- Lead sponsor
- National Institute of Mental Health (NIMH)
- Sponsor type
- US National Institutes of Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00043654
- Sponsor's protocol ID
- 020251
- Other IDs
- 02-M-0251
- Status last verified
- 25 Jun 2007
- First submitted
- 9 Aug 2002
- Last updated
- 2 Jul 2017
- Results posted
- No
Publications
Sapolsky RM. Stress, Glucocorticoids, and Damage to the Nervous System: The Current State of Confusion. Stress. 1996 Jul;1(1):1-19. doi: 10.3109/10253899609001092.
PubMed 9807058
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Antiglucocorticoid Therapy in Bipolar Depression With Mifepristone (RU486)
- ClinicalTrials.gov ID
- NCT00043654
- Acronym / sponsor ID
- 020251
- Conditions
- Bipolar Disorder
- Keywords
- Antidepressant, Manic-Depressive Disorder, Cortisol, Neuroendocrine, Cognition, Bipolar, Bipolar Disorder, BPD
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 110 participants
- Lead sponsor
- National Institute of Mental Health (NIMH)US National Institutes of Health
- Study start
- 7 Aug 2002
- Study completion
- 25 Jun 2007
- First posted
- 12 Aug 2002 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Bipolar Depression is a severe illness with high rates of psychiatric comorbidity and increased mortality related to suicide and medical illness. Hypothalamic pituitary axis (HPA) hyperactivity are found in bipolar disorder related to depression and mixed states. Patients with bipolar disorder also have cognitive difficulties and endocrine disturbances may contribute to such dysfunction. Antiglucorticoid therapies are novel treatments of mood disorder. Preliminary data in psychotic depression suggesting that mifepristone (RU-486), a glucocorticoid receptor antagonist, has antidepressant and salutary cognitive effects in a matter of days. In this study we examine the effects of mifepristone in severe bipolar depression in a parallel, double blind placebo controlled experiment. Bipolar subjects maintained on either lithium or valproate, after washout or prior antidepressants have a detailed neuroendocrine assessment. Patients approximately or almost 75 will receive eight days of mifepristone versus placebo after which patients are blindly crossed over to the opposite arm. Patients and a group of matched controls approximately or almost 35 will be compared with neuroendocrine, cognitive, and neurophysiologic testing to fully characterize their phenotype and explore biomarkers of response. It is hypothesized that stigmata of HPA axis hyperactivity and cognitive impairment will be predictive of response to antiglucocorticoid therapy with mifepristone.
Detailed description
Bipolar Depression is a severe illness with high rates of psychiatric comorbidity and increased mortality related to suicide and medical illness. Hypothalamic pituitary axis (HPA) hyperactivity are found in bipolar disorder related to depression and mixed states. Patients with bipolar disorder also have cognitive difficulties and endocrine disturbances may contribute to such dysfunction. Antiglucorticoid therapies are novel treatments of mood disorder. Preliminary data in psychotic depression suggesting that mifepristone (RU-486), a glucocorticoid receptor antagonist, has antidepressant and salutary cognitive effects in a matter of days. In this study we examine the effects of mifepristone in severe bipolar depression in a parallel, double blind placebo controlled experiment. Bipolar subjects maintained on either lithium or valproate, after washout or prior antidepressants have a detailed neuroendocrine assessment. Patients approximately or almost 75 will receive eight days of mifepristone versus placebo after which patients are blindly crossed over to the opposite arm. Patients and a group of matched controls approximately or almost 35 will be compared with neuroendocrine, cognitive, and neurophysiologic testing to fully characterize their phenotype and explore biomarkers of response. It is hypothesized that stigmata of HPA axis hyperactivity and cognitive impairment will be predictive of response to antiglucocorticoid therapy with mifepristone.
Study design
- Primary purpose
- Treatment
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Male or female inpatients in need of treatment for severe bipolar depression.
- 18-75 years of age.
- Women of childbearing potential must be using an adequate form of contraception as defined by one of the following: 1) a barrier method and 2) oral contraceptives plus a barrier method (women who are on an OCP will be kept on it others must agree to use only a barrier method).
- DSM-IV diagnosis of bipolar depression I/II, severe, with or without psychotic features.
- A current major depressive episode of at least 6 weeks' duration.
Key exclusion criteria (22 listed)
- Women who are pregnant, intending to become pregnant in the next month or breast-feeding.
- Treatment with any of the following therapies within the specified interval prior to baseline: Fluoxetine - 4 weeks; Investigational compounds 4 weeks; MAOIs 1 week; Other antidepressants 1 week.
- Contraindication or history of hypersensitivity to mifepristone as well as cortisol, and CRH.
- Clinically significant organ system disease where mifepristone would be contraindicated or interfere with medical treatment.
- Have evidence of any disorder that represents a contraindication to the use of mifepristone (such as adrenal disease or a condition requiring chronic corticosteroid administration).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Mifepristone | Drug | – |
Primary outcome
Not reported in the source record.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Background: PubMed 9807058Sapolsky RM. Stress, Glucocorticoids, and Damage to the Nervous System: The Current State of Confusion. Stress. 1996 Jul;1(1):1-19. doi: 10.3109/10253899609001092.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Mifepristone in people with Bipolar Disorder, run by National Institute of Mental Health (NIMH) at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00043654, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Jul 2017.