Dehydroepiandrosterone (DHEA) as Augmentation of Standard An-tidepressants in Treatment-resistant Depression: a Randomized Controlled Trial (DARE-Trial) - A Multicenter, Randomized, Double-blind, Placebo-controlled Trial With Group Sequential Design
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 320
- 试验地点
- 9
- 主要终点
- Change score in MADRS (Montgomery-Asberg-Depression Rating Scale)
研究概览
简要总结
Major depressive disorder (MDD) is a major contributor to impaired health worldwide. Initial antidepressant treatment of MDD does not lead to response in up to 50 % of patients. TRD (Treatment Resistant Depression) is associated with increased rates of recurrence, mortality as well as increased treating costs compared to MDD. Treatment op-tions for TRD remain limited with lithium, quetiapine and esketamine being the only recommended and approved augmentation strategies in the EU. Dehydroepiandrosterone (DHEA), an endogenous steroid hormone, is a promising, safe and tolerable adjunctive treatment op-tion. DHEA has been meta-analytically shown to elicit antidepressant effects and to be safe both in MDD and for depressive symptoms in other medical diseases. However, previous RCTs (Randomized con-trolled trial) were small and no study has yet tested the antidepressant potential of adjunct treatment with DHEA in patients with TRD.
Primary objective To determine whether add-on 100 mg/d DHEA to continued standard antidepressant medication improves depression to a greater extent than add-on placebo in subjects with treatment-resistant depression.
Secondary objectives To determine whether add-on 100 mg/d DHEA to continued standard antidepressant medication improves response rates, remission rates, patients' impression of change, clinician's impression of severity and change, quality of life, social functioning and self-report depression se-verity to a greater extent than adjunct placebo in subjects with TRD. Furthermore, changes in glucose, glycosylated hemoglobin (HbA1c), total, HDL- and LDL-cholesterol, C-reactive protein (CRP), and inter-leukin-6 levels from baseline to week 6 will be determined.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patient provided written informed consent
- •,The patient is capable of giving consent (has sufficient knowledge of German and clearly understands the nature, significance and scope, including risks, of the medical procedure)
- •The patients is aged between 18 and 75 years (≥ 18 and ≤ 75)
- •The patient has an episode of major depression according to DSM 5 (Diagnostic and Statistical Manual of Mental Disorders, 5th edi-tion)
- •The patient has treatment-resistant depression (TRD), defined as non-response to at least one 4-week antidepressant treatment trial (including the current treatment) in the index episode (correspond-ing to level 1 resistance to treatment failure according to the Maudsley staging method)
- •The patient has a Montgomery-Asberg Depression Rating Scale (MADRS) score of ≥ 20
- •The patient is receiving antidepressant medication (SSRI or SNRI or tricyclic antidepressant or mirtazapine or bupropion) for at least 4 weeks, the dosage is at least at the approved minimum thera-peutic dosage and has been unchanged for at least 14 days prior to screening visit.
- •The patient had less than three (<3) treatment attempts with anti-depressants in the current MDE (current treatment attempts not in-cluded).
排除标准
- •Exclusion Criteria Related to psychiatric diagnosis
- •The patient has current clinically significant suicidal ideation with intent, corresponding to a score of 4 or 5 for ideation on the C-SSRS, or a suicidal attempt within the past 6 months, as indicated by the C-SSRS at screening visit
- •The patient fulfills the criteria for psychotic depression according to DSM-5
- •The patient meets the criteria for schizophrenia, schizoaffective disorder or bipolar disorder in M.I.N.I according to DSM-5
- •The patient meets the criteria for a dependency disorder in the M.I.N.I. for DSM-5
- •The patient has dementia or moderate to severe cognitive impair-ment. Exclusion Criteria Related to IMP
- •The Patient is currently taking DHEA or has taken it within the last 14 days prior to screening visit.
- •The patients is currently taking hormone replacement therapy with sex hormones (other than contraceptives)
- •The patient has undiagnosed genital bleeding
- •The patient has untreated endometrial hyperplasia The patient has or has had sex hormone-dependent cancer (e.g. breast cancer, ovarian cancer, endometrial cancer, prostate can-cer)
- •The patient is allergic or has contraindication to DHEA or lactulose and cellulose
- •The patient has previous diagnosis of chronic kidney disease stage G3b (or higher) or GFR < 30 ml/min.
- •The patient has diagnosis of prostatic hyperplasia. Exclusion Criteria Related to standard antidepressant medication (AxMP)
- •The Patient is taking antidepressants other than those listed as in-clusion criterion (SSRI, SNRI, tricyclic antidepressants, bupropion, mirtazapine)
- •The patient is taking psychotropic medication, e.g. antipsychotics, anticonvulsants, lithium or Johannis herbs. Allowed substances in-clude benzodiazepines, non-benzodiazepines (Zopiclon, Zolpidem or Eszopiclon) and antidepressants listed under inclusion criteria.
- •The patient is using non-selective, irreversible MAO inhibitors (e.g. tranylcypromine) or selective, reversible MAO-A inhibitors (e.g. moclobemide) or the reversible non-selective MAO inhibitor line-zolid
- •The patient has insulin-dependent diabetes mellitus General Safety Exclusion Criteria
- •The patient has an untreated and unstable general medical condi-tion (e.g. hypertension with end organ damage or hypertensive de-railment)
- •The patient has a medical history of liver failure and/or bilirubin above 3 times the normal range and reduced total protein
- •The patient is pregnant or breastfeeding.
- •The patient of childbearing age shows an unwillingness to use an effective contraceptive method (defined as a Pearl Index < 1)
- •The patient currently has or has a history of venous thromboembo-lism (VTE) (deep vein thrombosis, pulmonary embolism)
- •The patient currently has or has a history of arterial thromboem-bolic disease (e.g. angina pectoris, myocardial infarction, stroke)
- •The patient has a thrombophilic disease (e.g. protein C, protein S or antithrombin deficiency)
- •The patient has porphyria
- •The patient has clinically significant untreated hypothyroidism
- •The patient has clinically significant abnormalities in the 12-lead ECG (e.g. prolongation of the QTc interval ≥ 500 ms) as performed during screening visit
- •The patient is a vulnerable person (defined as: persons deprived their liberty, confined to an institution by court or administrative or-der, persons that may have Insufficient power, intelligence, educa-tion, resources, strength, or other needed attributes to protect their own interests, or unable to explicitly give consent)
- •The patient might be dependent on representative of the sponsor, the investigator or the trial site The patient is currently participating in another interventional clini-cal trial.
- •Laboratory Exclusion Criteria
- •The patient's laboratory values show clinically significant abnor-malities
- •The patient currently has liver disease with liver-specific levels out-side the age- and gender-specific reference intervals [elevations of GOT or GPT above 3 times the upper normal value (ULN)]
研究组 & 干预措施
Placebo
Placebo to continued standard antidepressant medication
干预措施: Placebo (Drug)
DHEA
100 mg/d DHEA to continued standard antidepressant medication
干预措施: Dehydroepiandrosterone (DHEA) (Drug)
结局指标
主要结局
Change score in MADRS (Montgomery-Asberg-Depression Rating Scale)
时间窗: 6 weeks
The MADRS is a rating scale to measure depression severity. Each MADRS item is rated on a 0 to 6 scale. Total score range from 0-60, where higher MADRS scores indicate higher levels of depressive symptoms.
次要结局
- MADRS response and remission(6 weeks)
- Adverse event-related treatment discontinuation(6 weeks)
研究者
Prof. Dr. Christian Otte
Professor of Psychiatry
Charite University, Berlin, Germany