Mifepristone Used to Treat Patients With Non-psychotic Major Depressive Disorder Referred for Bilateral Electroconvulsive Therapy (ECT)

Depression Clinical Trial

Official title:

A Double-blind, Placebo-controlled Study of Mifepristone in Patients With Non-psychotic Major Depressive Disorder Referred for Bilateral Electroconvulsive Therapy (ECT)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00285818
• Other study ID #: 2HSE450
• Secondary ID: 12062
• Status: Completed
• Phase: N/A
• First received: January 31, 2006
• Last updated: September 15, 2010
• Start date: January 2003
• Est. completion date: April 2009

Study information

• Verified date: September 2010
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to see whether the medication mifepristone is an effective and tolerable treatment for increasing the clinical effectiveness of electroconvulsive therapy (ECT) and protecting cognitive function during ECT. Both Mifepristone and ECT appear to normalize hyperfunctioning of the hypothalmic-pituitary-adrenal (HPA) axis, which has been found among patients with major depression referred for ECT. The combination of these two treatments in major depression may lead to a more rapid clinical response than ECT alone. Additionally, there appears to be a connection between pre-ECT higher cortisol levels due to HPA axis hyperfunctioning and post-ECT cognitive impairment. Administration of mifepristone prior to and during ECT treatment may reduce cortisol levels and reduce the incidence of cognitive impairment observed after ECT.

Description:

Patients referred to the Stanford ECT Service who provide informed consent for this study will be screened for eligibility.

Day -4 to 0: Screening (visit 1) will occur three to six days prior to the first ECT treatment. Screening procedures will include: Psychiatric interviews and ratings (including MINI, Hamilton Depression Rating Scale and Clinician's Global Impression) and review/retrieval of results of pre-ECT physical exam, ECG, chest x-ray, laboratory evaluations (including comprehensive metabolic panel, comprehensive blood count, and urine toxicology), and vital signs from the subject's medical record. A urine pregnancy test will be included for females of childbearing potential. Concomitant medications and pre-existing health issues will be recorded. Subjects who are deemed eligible for this study will then undergo a battery of neuropsychiatric assessments and will be admitted to GCRC for collection of blood samples to measure adrenocorticotropin (ACTH) and cortisol levels. These samples will be collected hourly beginning at 1pm and ending at 4pm.

Day 1: Subjects will be randomized 1:1 to receive either mifepristone 600mg or placebo each day at bedtime beginning two days prior to the first ECT treatment. Subjects will be administered study medication on Day 1 through Day 8.

Day 3: Subjects will be interviewed with the Hamilton Depression Rating Scale and Clinician's Global Impression before their first ECT treatment.

Day 11: (visit 2) assessments will include psychiatric ratings (including Hamilton Depression Rating Scale and Clinician's Global Impression) and a battery of neuropsychiatric assessments. Adverse events and concomitant medications will be reviewed and recorded. Subjects will be admitted to the GCRC for collection of blood samples to measure ACTH and cortisol levels. Samples will be collected hourly beginning at 1pm and ending at 4pm.

Day 18: (visit 3) assessments will include psychiatric ratings (including Hamilton Depression Rating Scale and Clinician's Global Impression). Adverse events and concomitant medications will be reviewed and recorded. Clinical laboratory assessments will be completed (including a urine pregnancy test for females, comprehensive metabolic panel, comprehensive blood count, urine toxicology, and ECG.) Final visit: (visit 4) will occur 24-72 hours after the last ECT treatment. Assessments will include psychiatric ratings (including Hamilton Depression Rating Scale and Clinician's Global Impression) and a battery of neuropsychiatric assessments. Adverse events and concomitant medications will be reviewed and recorded. A urine pregnancy test will be completed for females.

In addition to the ECT treatment consent, the following materials will be collected from the participant's medical record for every ECT treatment: ECT treatment orders, ECT procedure note and the results of each pre-ECT Montgomery-Asberg Depression Rating Scale (MADRS). ECT treatments at Stanford's ECT Service run every Monday, Wednesday and Friday.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: April 2009
• Est. primary completion date: January 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

Inclusion Criteria:To be considered for participation in the study, subject must meet all of the following criteria:

1. Meets DSM-IV criteria for Major Depressive Episode without psychotic features.

2. 18-75 years of age and able to provide legal consent.

3. Referred to Stanford ECT service by treating physician for bilateral electroconvulsive therapy with inpatient hospitalization.

4. Completed process for consenting to the clinical use of ECT according to California State law.

5. Females of childbearing potential must be using a double-barrier method of contraception during the study and for 30 days after the study (modified 6-2003)

Exclusion Criteria:Subjects will be excluded from participation if they meet any of the following criteria:

1. Treatment with ECT in the 6 months prior to screening.

2. Meets criteria for drug or alcohol abuse or dependence in the 6 months prior to screening.

3. Use of alcohol or illegal drugs within seven days of randomization or during study.

4. Presence of unstable or untreated cardiovascular disease, hypertension, or endocrine disorder as determined by investigator.

5. Use of antipsychotic, antidepressant, or other prescription medications unless dose is stable for at least 7 days prior to randomization.

6. Use of any investigational treatment within 30 days of randomization.

7. Current pregnancy.

8. Current lactation.

9. Previous allergic reaction to mifepristone or drugs of similar chemical structure. (added 6-2003)

10. Use of any oral contraceptives or other drugs that may result in adverse drug-mifepristone interaction effects. A 30-day wash out period for oral contraceptives is required before mifepristone begins.

Study Design

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

Related Conditions & MeSH terms

• Depression
• Depressive Disorder
• Depressive Disorder, Major

Intervention

Drug:
• Mifepristone

Locations

Country	Name	City	State
United States	Stanford University School of Medicine	Stanford	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Hamilton Depression Rating Scale		Screening to Final Visit	No
Secondary	Neuropsychiatric Assessments		Time 1 versus post ECT time points	No
Secondary	Does mifepristone act as a protective agent to cognitive function as measured by the difference in neuropsychiatric assessments between placebo and mifepristone groups		5 weeks	No