Childhood trauma related depression
Conditions
Interventions
Trade Name: Korlym
Product Name: Mifepristone
Pharmaceutical Form: Coated tablet
Pharmaceutical form of the placebo: Coated tablet
Route of administration of the placebo: Oral use
Sponsors
Amsterdam UMC, location VUmc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Mastery of Dutch language • Age of = 18 years of age and able to give written IC • Participant agrees to be randomized • Moderate to severe depression Score = 26 on the Inventory of Depressive Symptoms-Self Report (IDS-SR) • DSM-5 diagnosis of major depression disorder (MDD), confirmed with clinical interview (MINI) • Moderate to severe childhood trauma (CT) before the age of 18 Score above validated cut-off for moderate to severe CT on one or more of the following domains using the Childhood Trauma Questionnaire (CTQ): ? physical neglect: score = 10 ? emotional neglect: score = 15 ? sexual abuse: score = 8 ? physical abuse: score = 10 ? emotional abuse: score = 13 • A female participant is eligible to participate if she is not pregnant or breastfeeding, and one of the following conditions applies: o Is not a WOCBP o Is a WOCBP and agrees to use an acceptable non-hormonal contraceptive method (e.g. condom, also if hormonal contraceptive method is used) during the intervention period and up to 1 month after the intervention. A WOCBP must have a negative highly sensitive pregnancy test before the first dose of the study intervention. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 158 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: A potential participant who meets any of the following criteria will be excluded from participation in this study: • Primary diagnosis of post-traumatic stress disorder (PTSD) or Acute Stress disorder (ASD) • Lifetime diagnosis of borderline personality disorder (BPD) • Current alcohol/drug dependence or other severe psychiatric comorbidity (e.g. bipolar disorder, schizophrenia) that requires clinical attention. • Start of other forms of depression treatment in the week before or after the start of intervention. • Female participant being a WOCBP who do not agree to use an acceptable non-hormonal contraceptive method (e.g. condom, also if hormonal contraceptive method is used) during the intervention period and up to 1 month after the intervention. • Female participants that are pregnant or breastfeeding. Pregnancy is excluded using a negative highly sensitive pregnancy test before the first dose of the study medication during the baseline visit. • Female participants that have a history of unexplained vaginal bleeding or endometrial changes • Chronic adrenal insufficiency • Current use of: o Medications containing CYP3A4-inhibitors, as an interaction of CYP3A4-inhibitors and mifepristone leads to higher mifepristone plasma levels and increases the chance of having side effects. This also includes the consumption of grapefruit juice during the intervention o Medications containing CYP3A4-inductors, as an interaction of CYP3A4-inductors and mifepristone leads to lower mifepristone plasma levels and decreases the chance of having a beneficial effect. This also includes the consumption of St John’s worth /hypericum perforatum during the intervention. o Glucocorticoid antagonists within 1 week before possible start of trial treatment. o Systemic corticosteroids. Topical corticosteroid treatment are acceptable, with the exception of inhaled corticosteroids (inhalators). Before randomization, all currently used medications will be reviewed by a pharmacologist from the hospital pharmacy to prevent toxicity or interaction with mifepristone.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether mifepristone (7-day, 600mg/day) added to treatment as usual (TAU), is more efficacious than placebo in reducing depressive symptom severity (Inventory of Depressive Symptoms-Self Rated questionnaire; IDS-SR) in patients with CT-related depression, 6 weeks after the start of intervention. ;Secondary Objective: 1. To investigate whether mifepristone (7-day, 600mg/day) added to treatment as usual (TAU), is more efficacious than placebo in improving: • Depression remission, 6 weeks after the start of intervention • Short-term depressive symptom severity and depression remission, 1 week after the start of intervention • Long-term depressive symptom severity and depression remission, 12 weeks and 6 months after the start of intervention • Treatment response (50% decrease in IDS-SR score), from 1 week to 6 months after the start of intervention 2. To identify other clinical outcomes related to mifepristone treatment: disability, sleep, subjective stress and if present suicidal ideation and behavior, from 1 week to 6 months after the start of intervention 3. In addition, biological measurements (blood, hair, saliva) are used to assess for whom and how the mifepristone treatment is most efficacious, including: cortisol levels, DNA regulation and mifepristone plasma levels. ;Primary end point(s): Depressive symptom severity (IDS-SR score), 6 weeks after the start of intervention. ;Timepoint(s) of evaluation of this end point: 6 weeks after the start of intervention | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. • Depression remission (<14 on IDS-SR, confirmed with the Mini International Neuropsychiatric Interview; MINI), 6 weeks after the start of intervention • Short-term depressive symptom severity (IDS-SR) and depression remission (MINI), 1 week after the start of intervention • Long-term depressive symptom severity (IDS-SR) and depression remission (MINI), 12 weeks and 6 months after the start of intervention • Treatment response (50% decrease in IDS-SR score), from 1 week to 6 months after the start of intervention 2. To identify other clinical outcomes related to mifepristone treatment: disability (WHO Disability Schedule 2.0; WHO-DAS), sleep (Pittsburgh Sleep Quality Index; PSQI), subjective stress (Perceived Stress Scale; PSS) and if present suicidal ideation and behavior (Columbia-Suicide Severity Rating Scale), from 1 week to 6 months after the start of intervention 3. To better understand how and for who a mifepristone treatment is efficacious, several stress related biomarkers are assessed: • Saliva cortisol levels, at baseline and post-intervention 1, and 6 weeks after the start of intervention • Hair cortisol levels, at baseline and 6 weeks after randomization • Blood biomarkers (inflammatory biomarkers and (epi)genetic assessment), at baseline and 1 and 6 weeks after the start of intervention • Mifepristone plasma levels at post-intervention, 1 week after the start of intervention ;Timepoint(s) of evaluation of this end point: See E.5.2 | — |
Countries
Netherlands
Contacts
Public ContactDepartment of Psychiatry
Amsterdam UMC, location VUmc
Outcome results
None listed