Major Depressive DisorderPhase 2RESET-mNCT05217758
RESET-medication Glucocorticoid Receptor (GR) Blockade As Disease Modifying Treatment for Depression with Childhood Trauma
A Phase 2 study testing Mifepristone in people with Major Depressive Disorder and Childhood Trauma, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
Trial summary
Depression is a recurrent debilitating psychiatric disorder with a lifetime prevalence of 20%. Even though antidepressants and psychotherapy are often effective, a substantial proportion of patients does not respond to currently used evidence-based treatments. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Major Depressive Disorder, Childhood Trauma
- What is being tested?
- Mifepristone
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 158 participants
- Where
- 1 siteNetherlands
- Study dates
- 9 Dec 2021to 12 Nov 2024
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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 (M.I.N.I.-S)
- 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):
Show all 11Show fewer
- physical neglect: score ≥ 10
- emotional neglect: score ≥ 15
- sexual abuse: score ≥ 8
- physical abuse: score ≥ 10
- emotional abuse: score ≥ 13
Who cannot join
- Primary diagnosis of post-traumatic stress disorder (PTSD) or Acute Stress Disorder (ASD)
- Lifetime diagnosis of borderline personality disorder (BPD)
- Other lifetime severe psychiatric comorbidity (e.g. bipolar disorder, schizophrenia) or current alcohol/drug dependence that requires clinical attention.
- Start of other forms of depression treatment in the week before or after the start of the intervention.
- Female participant being a WOCBP and who does not want to use a non-hormonal contraceptive method (e.g. condom) during the intervention period and up to 1 month after the intervention.
- Female participants that are pregnant or breastfeeding.
Show all 13Show fewer
- Female participants that have a history of unexplained vaginal bleeding or endometrial changes.
- Chronic adrenal insufficiency (contraindication for mifepristone).
- Current use of:
- Medications containing CYP3A4-inhibitors
- Medications containing CYP3A4-inductors
- Glucocorticoid antagonists within 1 week before possible start of trial treatment.
- Systemic corticosteroids. Topical corticosteroid treatment are acceptable, with the exception of inhaled corticosteroids (inhalators).
Trial locations and contacts
1 site in 1 country.
Netherlands1 site
Amsterdam UMC, location VUmc
Amsterdam, North Holland, 1081HV
About this study
Official title: RESET-medication: Glucocorticoid Receptor (GR) Blockade As Diseasemodifying Treatment for Depression with Childhood Trauma
Depression is a recurrent debilitating psychiatric disorder with a lifetime prevalence of 20%. Even though antidepressants and psychotherapy are often effective, a substantial proportion of patients does not respond to currently used evidence-based treatments. The heterogeneous nature of depressive symptoms is a major obstacle for the development of novel effective treatments, and targeted treatments for depression are currently lacking.
The investigators propose a targeted disease-modifying treatment for the clinically distinct form of depression related to childhood trauma (CT, emotional/ physical/sexual abuse or neglect before the age of18). CT-related depression is critically different from non-CT depression: it emerges earlier in life with more severe and recurrent symptoms and less favorable responses to treatment. With an average 25% prevalence in depression, there is a large and unmet need for therapeutic strategies to treat depression in individuals with substantial CT.
The GR is the major cortisol receptor in the brain and rodent studies have shown that GR blockade at adult age can reverse the effects of early-life adversity. Therefore, GR blockade is a potential novel treatment for CT-related depression but this has never been investigated. Based on the underlying stress neurobiology, the aim is to investigate whether the biological sequelae of excessive stress due to CT can be targeted by blocking the glucocorticoid receptor (GR) using the generic drug mifepristone.
Read the detailed description
Rationale: Depression is a recurrent debilitating psychiatric disorder with a lifetime prevalence of 20%. Even though antidepressants and psychotherapy are often effective, a substantial proportion of patients does not respond to currently used evidence-based treatments. The heterogeneous nature of depressive symptoms is a major obstacle for the development of novel effective treatments, and targeted treatments for depression are currently lacking. The investigators propose a targeted disease-modifying treatment for the clinically distinct form of depression related to childhood trauma (CT, emotional/physical/sexual abuse or neglect before the age of 18). CT-related depression is critically different from non-CT depression: it emerges earlier in life with more severe and recurrent symptoms and less favorable responses to treatment.
With an average 25% prevalence in depression, there is a large and unmet need for therapeutic strategies to treat depression in individuals with substantial CT. Based on the underlying stress neurobiology, the aim is to investigate whether the biological sequelae of excessive stress due to CT can be targeted by blocking the glucocorticoid receptor (GR) using the generic drug mifepristone. The GR is the major cortisol receptor in the brain and rodent studies have shown that GR blockade at adult age can reverse the effects of early-life adversity.
Therefore, GR blockade is a potential novel treatment for CT-related depression but this has never been investigated.
Objective: The investigators will test the hypothesis that treatment with the GR-antagonist mifepristone is more effective than placebo to reduce depressive symptom severity in CT-related depression.
Study design: Placebo-controlled double-blind randomized controlled trial (RCT).
Study population: 158 adult patients (male/female, 18+ years), with depression and moderate to severe childhood trauma (CT).
Intervention: Patients are randomized to treatment with the GR antagonist mifepristone (1200 mg/day for 7 days, n=79) or placebo (daily for 7 days, n=79), with both groups receiving usual care for depression.
Main study parameters/endpoints: Improvement of depressive symptoms, as measured with the Inventory of Depressive Symptomatology - Self Rated (IDS-SR, continuous scale) questionnaire, 6 weeks after the start of the intervention.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: For screening, online questionnaires will be completed requiring 10 minutes. After inclusion and randomization, the experimental protocol consists of three face-to- face meetings at baseline (T0, 2,5hrs), week 1 (T1, 1hr), week 6 (T2, 1hr), and two online follow-up meetings at 12 weeks (T3, 0.75hr) and 6 months (T4, 0.75hr). Study medication will be dispensed after the baseline measurements and taken once daily for 7 consecutive days.
Clinical measurements consist of clinical interviews, questionnaires, blood and saliva samples (T0, T1, T2), and hair samples (T0, T2). A subgroup of participants (n=60, 30 per intervention group) will be asked to participate in (f)MRI scans at baseline (T0) and post-intervention (T2;1hr per scan session).
Mifepristone has been clinically used for Cushing's syndrome (antiglucocorticoid effects) and termination of pregnancy (anti-progesterone effects) for several decades. Mifepristone is generally well-tolerated, and several double-blind studies using the identical duration and dose have shown (7 days, 1200 mg) that the safety profile of mifepristone is comparable to that of placebo treatment, and study dropouts due to side effects were higher for placebo (1.6%) than for mifepristone (1.4%). The most common adverse events (AEs) were nausea, headache, dizziness, and a dry mouth and were comparable between the mifepristone and placebo groups. With regard to mifepristone's progesterone receptor activity and its indication for pregnancy termination, in the current RCT women of childbearing potential (WOCBP) who do not agree to use a non-hormonal contraceptive method (e.g. condom) during the intervention and up to 1 month after the intervention, are strictly excluded from participating in this study.
Since mifepristone may interfere with the effectiveness of hormonal contraceptive methods, a non-hormonal method (e.g. condom) should be used, also in case of continued hormonal contraceptive use during the intervention and up to 1 month after the intervention. Thus, besides men and non-WOCBP, WOCBP can only participate if not currently breastfeeding, with confirmed negative pregnancy test and use of a non-hormonal contraceptive method.
- Conditions
- Major Depressive Disorder, Childhood Trauma
- Being tested
- Mifepristone, Placebo
- Keywords
- RESET, childhood maltreatment, early life stress, Glucocorticoid Receptor (GR)
- Medical subject headings
- Depressive Disorder, Major, Stress, Psychological
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MifepristoneDrug
1200 mg/day, once daily, 7 days
PlaceboDrug
Placebo, once daily, 7 days
| Study group | Role | What they receive |
|---|---|---|
| Mifepristone | Experimental | Glucocorticoid Receptor (GR) blockade using the generic drug mifepristone Receives: Drug: Mifepristone |
| Placebo | Placebo comparator | Not described Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Depressive symptom severity at post-treatment
Depressive symptom severity in patients with CT-related depression, measured with the Inventory of Depressive Symptomatology - Self Report (IDS-SR, with a total score ranging from 0 to 84, where higher scores indicate higher severity of depressive symptoms)
Measured: 6 weeks after the start of the intervention
Secondary outcomes (3)
Depressive symptom severity at short-term
Depressive symptom severity in patients with CT-related depression, measured with the Inventory of Depressive Symptomatology - Self Report (IDS-SR, with a total score ranging from 0 to 84, where higher scores indicate higher severity of depressive symptoms)
Measured: 8 days after the start of the intervention
Depressive symptom severity at long-term
Depressive symptom severity in patients with CT-related depression, measured with the Inventory of Depressive Symptomatology - Self Report (IDS-SR, with a total score ranging from 0 to 84, where higher scores indicate higher severity of depressive symptoms)
Measured: 3 months and 6 months after the start of the intervention
Remission in CT-related depression
The presence or absence of DSM-5 Major Depressive Disorder (MDD), identified using the Major Depressive Disorder (MDD) section of the Mini International Neuropsychiatric Interview (M.I.N.I.-S).
Measured: Up to 6 months after the start of the intervention
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Feb 2022
- Study start9 Dec 2021
- Primary completion9 Aug 2024
- Study completion12 Nov 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (11)Papers the sponsor has linked to this study.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Amsterdam UMC, location VUmcThe 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
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 158 participants (actual)
Sponsor and investigators
- Lead sponsor
- Amsterdam UMC, location VUmc
- Sponsor type
- University, hospital or other
- Collaborators
- Netherlands Brain Foundation, Corcept Therapeutics
- Responsible party
- Principal investigator, Christiaan Vinkers, Amsterdam UMC, location VUmc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05217758
- Sponsor's protocol ID
- RESET001
- Acronym
- RESET-m
- Status last verified
- Dec 2024
- First submitted
- 20 Dec 2021
- Last updated
- 6 Dec 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures and appendices)
Publications
Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.
PubMed 17074942McLaughlin KA, Green JG, Gruber MJ, Sampson NA, Zaslavsky AM, Kessler RC. Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication II: associations with persistence of DSM-IV disorders. Arch Gen Psychiatry. 2010 Feb;67(2):124-32. doi: 10.1001/archgenpsychiatry.2009.187.
PubMed 20124112Teicher MH, Samson JA. Childhood maltreatment and psychopathology: A case for ecophenotypic variants as clinically and neurobiologically distinct subtypes. Am J Psychiatry. 2013 Oct;170(10):1114-33. doi: 10.1176/appi.ajp.2013.12070957.
PubMed 23982148Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D, Freedman A, Sharma S, Pearson D, Plotsky PM, Meaney MJ. Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science. 1997 Sep 12;277(5332):1659-62. doi: 10.1126/science.277.5332.1659.
PubMed 9287218Arp JM, Ter Horst JP, Loi M, den Blaauwen J, Bangert E, Fernandez G, Joels M, Oitzl MS, Krugers HJ. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress. Neurobiol Learn Mem. 2016 Sep;133:30-38. doi: 10.1016/j.nlm.2016.05.009. Epub 2016 May 28.
PubMed 27246249Loi M, Sarabdjitsingh RA, Tsouli A, Trinh S, Arp M, Krugers HJ, Karst H, van den Bos R, Joels M. Transient Prepubertal Mifepristone Treatment Normalizes Deficits in Contextual Memory and Neuronal Activity of Adult Male Rats Exposed to Maternal Deprivation. eNeuro. 2017 Nov 2;4(5):ENEURO.0253-17.2017. doi: 10.1523/ENEURO.0253-17.2017. eCollection 2017 Sep-Oct.
PubMed 29098176Papilloud A, Veenit V, Tzanoulinou S, Riccio O, Zanoletti O, Guillot de Suduiraut I, Grosse J, Sandi C. Peripubertal stress-induced heightened aggression: modulation of the glucocorticoid receptor in the central amygdala and normalization by mifepristone treatment. Neuropsychopharmacology. 2019 Mar;44(4):674-682. doi: 10.1038/s41386-018-0110-0. Epub 2018 Jun 4.
PubMed 29941978Ding J, da Silva MS, Lingeman J, Chen X, Shi Y, Han F, Meijer OC. Late glucocorticoid receptor antagonism changes the outcome of adult life stress. Psychoneuroendocrinology. 2019 Sep;107:169-178. doi: 10.1016/j.psyneuen.2019.05.014. Epub 2019 May 16.
PubMed 31132569Zalachoras I, Houtman R, Atucha E, Devos R, Tijssen AM, Hu P, Lockey PM, Datson NA, Belanoff JK, Lucassen PJ, Joels M, de Kloet ER, Roozendaal B, Hunt H, Meijer OC. Differential targeting of brain stress circuits with a selective glucocorticoid receptor modulator. Proc Natl Acad Sci U S A. 2013 May 7;110(19):7910-5. doi: 10.1073/pnas.1219411110. Epub 2013 Apr 23.
PubMed 23613579Block TS, Kushner H, Kalin N, Nelson C, Belanoff J, Schatzberg A. Combined Analysis of Mifepristone for Psychotic Depression: Plasma Levels Associated With Clinical Response. Biol Psychiatry. 2018 Jul 1;84(1):46-54. doi: 10.1016/j.biopsych.2018.01.008. Epub 2018 Jan 31.
PubMed 29523415Linsen F, Broeder C, Sep MSC, Verhoeven JE, Bet PM, Penninx BWJH, Meijer OC, Vinkers CH. Glucocorticoid Receptor (GR) antagonism as disease-modifying treatment for MDD with childhood trauma: protocol of the RESET-medication randomized controlled trial. BMC Psychiatry. 2023 May 11;23(1):331. doi: 10.1186/s12888-023-04830-9.
PubMed 37170109
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- RESET-medication: Glucocorticoid Receptor (GR) Blockade As Diseasemodifying Treatment for Depression with Childhood Trauma
- ClinicalTrials.gov ID
- NCT05217758
- Acronym / sponsor ID
- RESET-m / RESET001
- Conditions
- Major Depressive Disorder, Childhood Trauma
- Keywords
- RESET, childhood maltreatment, early life stress, Glucocorticoid Receptor (GR)
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 158 participants (actual)
- Lead sponsor
- Amsterdam UMC, location VUmcUniversity, hospital or other
- Collaborators
- Netherlands Brain Foundation, Corcept Therapeutics
- Study start
- 9 Dec 2021 (actual)
- Primary completion
- 9 Aug 2024 (actual)
- Study completion
- 12 Nov 2024 (actual)
- First posted
- 1 Feb 2022 (actual)
- 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.
Depression is a recurrent debilitating psychiatric disorder with a lifetime prevalence of 20%. Even though antidepressants and psychotherapy are often effective, a substantial proportion of patients does not respond to currently used evidence-based treatments. The heterogeneous nature of depressive symptoms is a major obstacle for the development of novel effective treatments, and targeted treatments for depression are currently lacking.
The investigators propose a targeted disease-modifying treatment for the clinically distinct form of depression related to childhood trauma (CT, emotional/ physical/sexual abuse or neglect before the age of18). CT-related depression is critically different from non-CT depression: it emerges earlier in life with more severe and recurrent symptoms and less favorable responses to treatment. With an average 25% prevalence in depression, there is a large and unmet need for therapeutic strategies to treat depression in individuals with substantial CT.
The GR is the major cortisol receptor in the brain and rodent studies have shown that GR blockade at adult age can reverse the effects of early-life adversity. Therefore, GR blockade is a potential novel treatment for CT-related depression but this has never been investigated. Based on the underlying stress neurobiology, the aim is to investigate whether the biological sequelae of excessive stress due to CT can be targeted by blocking the glucocorticoid receptor (GR) using the generic drug mifepristone.
Detailed description
Rationale: Depression is a recurrent debilitating psychiatric disorder with a lifetime prevalence of 20%. Even though antidepressants and psychotherapy are often effective, a substantial proportion of patients does not respond to currently used evidence-based treatments. The heterogeneous nature of depressive symptoms is a major obstacle for the development of novel effective treatments, and targeted treatments for depression are currently lacking. The investigators propose a targeted disease-modifying treatment for the clinically distinct form of depression related to childhood trauma (CT, emotional/physical/sexual abuse or neglect before the age of 18). CT-related depression is critically different from non-CT depression: it emerges earlier in life with more severe and recurrent symptoms and less favorable responses to treatment.
With an average 25% prevalence in depression, there is a large and unmet need for therapeutic strategies to treat depression in individuals with substantial CT. Based on the underlying stress neurobiology, the aim is to investigate whether the biological sequelae of excessive stress due to CT can be targeted by blocking the glucocorticoid receptor (GR) using the generic drug mifepristone. The GR is the major cortisol receptor in the brain and rodent studies have shown that GR blockade at adult age can reverse the effects of early-life adversity.
Therefore, GR blockade is a potential novel treatment for CT-related depression but this has never been investigated.
Objective: The investigators will test the hypothesis that treatment with the GR-antagonist mifepristone is more effective than placebo to reduce depressive symptom severity in CT-related depression.
Study design: Placebo-controlled double-blind randomized controlled trial (RCT).
Study population: 158 adult patients (male/female, 18+ years), with depression and moderate to severe childhood trauma (CT).
Intervention: Patients are randomized to treatment with the GR antagonist mifepristone (1200 mg/day for 7 days, n=79) or placebo (daily for 7 days, n=79), with both groups receiving usual care for depression.
Main study parameters/endpoints: Improvement of depressive symptoms, as measured with the Inventory of Depressive Symptomatology - Self Rated (IDS-SR, continuous scale) questionnaire, 6 weeks after the start of the intervention.
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: For screening, online questionnaires will be completed requiring 10 minutes. After inclusion and randomization, the experimental protocol consists of three face-to- face meetings at baseline (T0, 2,5hrs), week 1 (T1, 1hr), week 6 (T2, 1hr), and two online follow-up meetings at 12 weeks (T3, 0.75hr) and 6 months (T4, 0.75hr). Study medication will be dispensed after the baseline measurements and taken once daily for 7 consecutive days.
Clinical measurements consist of clinical interviews, questionnaires, blood and saliva samples (T0, T1, T2), and hair samples (T0, T2). A subgroup of participants (n=60, 30 per intervention group) will be asked to participate in (f)MRI scans at baseline (T0) and post-intervention (T2;1hr per scan session).
Mifepristone has been clinically used for Cushing's syndrome (antiglucocorticoid effects) and termination of pregnancy (anti-progesterone effects) for several decades. Mifepristone is generally well-tolerated, and several double-blind studies using the identical duration and dose have shown (7 days, 1200 mg) that the safety profile of mifepristone is comparable to that of placebo treatment, and study dropouts due to side effects were higher for placebo (1.6%) than for mifepristone (1.4%). The most common adverse events (AEs) were nausea, headache, dizziness, and a dry mouth and were comparable between the mifepristone and placebo groups. With regard to mifepristone's progesterone receptor activity and its indication for pregnancy termination, in the current RCT women of childbearing potential (WOCBP) who do not agree to use a non-hormonal contraceptive method (e.g. condom) during the intervention and up to 1 month after the intervention, are strictly excluded from participating in this study.
Since mifepristone may interfere with the effectiveness of hormonal contraceptive methods, a non-hormonal method (e.g. condom) should be used, also in case of continued hormonal contraceptive use during the intervention and up to 1 month after the intervention. Thus, besides men and non-WOCBP, WOCBP can only participate if not currently breastfeeding, with confirmed negative pregnancy test and use of a non-hormonal contraceptive method.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Mifepristone | Experimental | Drug: MifepristoneGlucocorticoid Receptor (GR) blockade using the generic drug mifepristone |
| Placebo | Placebo comparator | Drug: Placebo |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- 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 (M.I.N.I.-S)
Key exclusion criteria (13 listed)
- Primary diagnosis of post-traumatic stress disorder (PTSD) or Acute Stress Disorder (ASD)
- Lifetime diagnosis of borderline personality disorder (BPD)
- Other lifetime severe psychiatric comorbidity (e.g. bipolar disorder, schizophrenia) or current alcohol/drug dependence that requires clinical attention.
- Start of other forms of depression treatment in the week before or after the start of the intervention.
- Female participant being a WOCBP and who does not want to use a non-hormonal contraceptive method (e.g. condom) during the intervention period and up to 1 month after the intervention.
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 |
|---|---|---|
| Mifepristone1200 mg/day, once daily, 7 days | Drug | Mifepristone |
| PlaceboPlacebo, once daily, 7 days | Drug | Placebo |
Primary outcome
Depressive symptom severity at post-treatment
Time frame: 6 weeks after the start of the intervention
Depressive symptom severity in patients with CT-related depression, measured with the Inventory of Depressive Symptomatology - Self Report (IDS-SR, with a total score ranging from 0 to 84, where higher scores indicate higher severity of depressive symptoms)
3 secondary outcomes
Depressive symptom severity at short-term
Time frame: 8 days after the start of the intervention
Depressive symptom severity at long-term
Time frame: 3 months and 6 months after the start of the intervention
Remission in CT-related depression
Time frame: Up to 6 months after the start of the intervention
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 6 Dec 2024.
- Background: PubMed 17074942Rush AJ, Trivedi MH, Wisniewski SR, Nierenberg AA, Stewart JW, Warden D, Niederehe G, Thase ME, Lavori PW, Lebowitz BD, McGrath PJ, Rosenbaum JF, Sackeim HA, Kupfer DJ, Luther J, Fava M. Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report. Am J Psychiatry. 2006 Nov;163(11):1905-17. doi: 10.1176/ajp.2006.163.11.1905.
- Background: PubMed 20124112McLaughlin KA, Green JG, Gruber MJ, Sampson NA, Zaslavsky AM, Kessler RC. Childhood adversities and adult psychiatric disorders in the national comorbidity survey replication II: associations with persistence of DSM-IV disorders. Arch Gen Psychiatry. 2010 Feb;67(2):124-32. doi: 10.1001/archgenpsychiatry.2009.187.
- Background: PubMed 23982148Teicher MH, Samson JA. Childhood maltreatment and psychopathology: A case for ecophenotypic variants as clinically and neurobiologically distinct subtypes. Am J Psychiatry. 2013 Oct;170(10):1114-33. doi: 10.1176/appi.ajp.2013.12070957.
- Background: PubMed 9287218Liu D, Diorio J, Tannenbaum B, Caldji C, Francis D, Freedman A, Sharma S, Pearson D, Plotsky PM, Meaney MJ. Maternal care, hippocampal glucocorticoid receptors, and hypothalamic-pituitary-adrenal responses to stress. Science. 1997 Sep 12;277(5332):1659-62. doi: 10.1126/science.277.5332.1659.
- Background: PubMed 27246249Arp JM, Ter Horst JP, Loi M, den Blaauwen J, Bangert E, Fernandez G, Joels M, Oitzl MS, Krugers HJ. Blocking glucocorticoid receptors at adolescent age prevents enhanced freezing between repeated cue-exposures after conditioned fear in adult mice raised under chronic early life stress. Neurobiol Learn Mem. 2016 Sep;133:30-38. doi: 10.1016/j.nlm.2016.05.009. Epub 2016 May 28.
- Background: PubMed 29098176Loi M, Sarabdjitsingh RA, Tsouli A, Trinh S, Arp M, Krugers HJ, Karst H, van den Bos R, Joels M. Transient Prepubertal Mifepristone Treatment Normalizes Deficits in Contextual Memory and Neuronal Activity of Adult Male Rats Exposed to Maternal Deprivation. eNeuro. 2017 Nov 2;4(5):ENEURO.0253-17.2017. doi: 10.1523/ENEURO.0253-17.2017. eCollection 2017 Sep-Oct.
- Background: PubMed 29941978Papilloud A, Veenit V, Tzanoulinou S, Riccio O, Zanoletti O, Guillot de Suduiraut I, Grosse J, Sandi C. Peripubertal stress-induced heightened aggression: modulation of the glucocorticoid receptor in the central amygdala and normalization by mifepristone treatment. Neuropsychopharmacology. 2019 Mar;44(4):674-682. doi: 10.1038/s41386-018-0110-0. Epub 2018 Jun 4.
- Background: PubMed 31132569Ding J, da Silva MS, Lingeman J, Chen X, Shi Y, Han F, Meijer OC. Late glucocorticoid receptor antagonism changes the outcome of adult life stress. Psychoneuroendocrinology. 2019 Sep;107:169-178. doi: 10.1016/j.psyneuen.2019.05.014. Epub 2019 May 16.
- Background: PubMed 23613579Zalachoras I, Houtman R, Atucha E, Devos R, Tijssen AM, Hu P, Lockey PM, Datson NA, Belanoff JK, Lucassen PJ, Joels M, de Kloet ER, Roozendaal B, Hunt H, Meijer OC. Differential targeting of brain stress circuits with a selective glucocorticoid receptor modulator. Proc Natl Acad Sci U S A. 2013 May 7;110(19):7910-5. doi: 10.1073/pnas.1219411110. Epub 2013 Apr 23.
- Background: PubMed 29523415Block TS, Kushner H, Kalin N, Nelson C, Belanoff J, Schatzberg A. Combined Analysis of Mifepristone for Psychotic Depression: Plasma Levels Associated With Clinical Response. Biol Psychiatry. 2018 Jul 1;84(1):46-54. doi: 10.1016/j.biopsych.2018.01.008. Epub 2018 Jan 31.
- Derived from this study: PubMed 37170109Linsen F, Broeder C, Sep MSC, Verhoeven JE, Bet PM, Penninx BWJH, Meijer OC, Vinkers CH. Glucocorticoid Receptor (GR) antagonism as disease-modifying treatment for MDD with childhood trauma: protocol of the RESET-medication randomized controlled trial. BMC Psychiatry. 2023 May 11;23(1):331. doi: 10.1186/s12888-023-04830-9.
- Study websiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Individual participant data that underlie the results reported in this article, after deidentification (text, tables, figures and appendices)
Related trials for Major Depressive Disorder
Not yet recruiting
Preventive and Personalized Digital Emotion Regulation Skills Intervention to Reduce Depression and Anxiety in Youths With Adverse Childhood Experiences
Adverse Childhood Experience, Depression / Major Depressive Disorder
RecruitingPhase 4
Biomarker-Guided Antidepressant Selection
Depression - Major Depressive Disorder, Treatment-resistant Depression (TRD)
Recruiting
Targeting Network Dysfunction in Apathy of Late-life Depression Using Digital Therapeutics
Major Depressive Disorder, Apathy
RecruitingObservational study
Student Precarity and Psychiatry
Depressive Disorder, Major, Generalized Anxiety Disorder
Not yet recruiting
Acute Intermittent Hypoxia Therapy for Depression
Major Depressive Disorder (MDD)
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 Major Depressive Disorder and Childhood Trauma, run by Amsterdam UMC, location VUmc at 1 site in Netherlands.
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 11 inclusion and 13 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 6 Dec 2024. 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 Netherlands. 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. Some participants in this study may receive a placebo. 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.
What does the primary outcome measure?
Depressive symptom severity at post-treatment (time frame: 6 weeks after the start of the intervention). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05217758, which also lists 11 linked publications.
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 6 Dec 2024.