RESET-medication: Glucocorticoid Receptor (GR) Blockade As Diseasemodifying Treatment for Depression with Childhood Trauma
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 158
- 试验地点
- 1
- 主要终点
- Depressive symptom severity at post-treatment
研究概览
简要总结
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.
详细描述
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).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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):
- •physical neglect: score ≥ 10
- •emotional neglect: score ≥ 15
- •sexual abuse: score ≥ 8
- •physical abuse: score ≥ 10
- •emotional abuse: score ≥ 13
排除标准
- •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.
- •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).
研究组 & 干预措施
Mifepristone
Glucocorticoid Receptor (GR) blockade using the generic drug mifepristone
干预措施: Mifepristone (Drug)
Placebo
干预措施: Placebo (Drug)
结局指标
主要结局
Depressive symptom severity at post-treatment
时间窗: 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)
次要结局
- Depressive symptom severity at short-term(8 days after the start of the intervention)
- Depressive symptom severity at long-term(3 months and 6 months after the start of the intervention)
- Remission in CT-related depression(Up to 6 months after the start of the intervention)
研究者
Christiaan Vinkers
Professor, Psychiatrist
Amsterdam UMC, location VUmc