INflammation-based Stratification for Immune-Targeted Augmentation in Major Depressive
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 240
- 试验地点
- 3
- 主要终点
- Change in depressive symptom severity (HDRS-17)
研究概览
简要总结
This is a randomised, double-blind, placebo-controlled clinical trial in which patients with major depressive disorder will receive augmentation through minocycline (MCO), celecoxib (CXB) or placebo.
详细描述
This project aims to repurpose two established anti-inflammatory compounds as adjuvant therapy for immune-mediated depression, in line with state-of-the-art research of the last 10 years. Immune-mediated depression represents a subtype which accounts for approximately 30% of depressive disorders. Patients with this immunosubtype are more likely to have a higher severity of depression, a lower quality of life and more somatic symptoms. Furthermore it is accompanied by a high incidence of treatment resistance. While their mechanisms of action completely differ from those of existing antidepressant treatment options, immunomodulatory drugs celecoxib and minocycline have proven their merit as add-on treatment in depressive episodes. They have been on the Belgian market for years and come with a known pharmacological and safety profile. Patient stratification at baseline based on inflammatory status will reveal which inflammatory subpopulation benefits most from each of the two investigated anti-inflammatory compounds. Additionally, our distinctive study design allows head-to-head comparison of both add-on therapies and will as such provide the last stepping stones towards clinical implementation of individualised treatment strategies in depression.
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male or female, 18-65 years inclusive.
- •Able and willing to give informed consent and take oral medication.
- •Physically healthy.
- •Diagnosis of Major Depressive Disorder by DSM-5 criteria, confirmed by the Mini International Neuropsychiatric Interview (MINI).
- •The current episode of depression has failed to remit to the current antidepressant treatment at the adequate dose (as defined in the Maudsley Prescribing guidelines). Relapse while taking an antidepressant is also considered a treatment failure.
- •Tolerant to the current antidepressant and having no planned changes in their current therapy for the duration of the study.
- •Stable on current treatment for a minimum of 4 weeks (6 weeks for fluoxetine) prior to baseline.
- •If female and of childbearing age, willing to use adequate contraceptive precautions and willing to take a pregnancy test at baseline.
排除标准
- •Primary diagnosis of a bipolar disorder, psychotic spectrum disorder, obsessive-compulsive disorder, eating disorder, post-traumatic stress disorder, or alcohol and/or substance use disorder according to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) (< 4 weeks before screening, excl. nicotine and caffeine).
- •Use of immunosuppressant or immunostimulant drugs within 21 days of screening (e.g., glucocorticoid treatment, methotrexate, etc.).
- •History of peptic ulcer disease or gastrointestinal (GI) bleeding.
- •Having an acute infection or inflammatory bowel disorder.
- •Current severe cardiovascular disease, congestive heart failure (NYHA-class II-IV), ischemic or thrombotic events or unstable coronary artery (incl. coronary artery bypass graft (CABG) surgery),
- •Liver impairment (alanine aminotransferase > 2x upper limit, serum albumin < 25 g/l or Child-Pugh Score ≥ 10)
- •Renal impairment (creatinine clearance < 30 mL/min).
- •Having received >14 days of tetracycline or non-steroidal anti-inflammatory medication within the previous 2 months, or having a history of sensitivity or intolerance to these classes of drugs.
- •Chronic severe hypertension (systolic BP > 170 mmHg).
- •Serology positive for hepatitis-B surface antigen, hepatitis-C antibodies or HIV antibodies.
- •Received electroconvulsive therapy < 2 months prior to screening.
- •Blood donation in 30 days prior to screening.
- •Pregnancy or breastfeeding.
- •Currently enrolled in an intervention study.
研究组 & 干预措施
High Sensitive C-reactive Protein (hs-CRP) > 3mg/L: Celecoxib + Treatment As Usual (TAU)
干预措施: Celecoxib (Drug)
High Sensitive C-reactive Protein (hs-CRP) < 3mg/L: Minocyclin + Treatment As Usual (TAU)
干预措施: Minocyclin (Drug)
High Sensitive C-reactive Protein (hs-CRP) < 3mg/L: Celecoxib + Treatment As Usual (TAU)
干预措施: Celecoxib (Drug)
High Sensitive C-reactive Protein (hs-CRP) < 3mg/L: Placebo + Treatment As Usual (TAU)
干预措施: Placebo (Drug)
High Sensitive C-reactive Protein (hs-CRP) > 3mg/L: Minocyclin + Treatment As Usual (TAU)
干预措施: Minocyclin (Drug)
High Sensitive C-reactive Protein (hs-CRP) > 3mg/L: Placebo + Treatment As Usual (TAU)
干预措施: Placebo (Drug)
结局指标
主要结局
Change in depressive symptom severity (HDRS-17)
时间窗: T0 -> T6 (12 weeks)
Change in severity of depression measured as the change in the 17-point scale of the Hamilton Depression Rating Scale (HDRS-17; score is ranging from 0 to 52, higher scores indicate higher severity of depressive symptoms) between baseline and endpoint
Remission rate of depression (HDRS-17)
时间窗: T0 -> T6 (12 weeks)
Rates of remission measured as a score of ≤7 on the 17-point scale of the Hamilton Depression Rating Scale (HDRS-17; score is ranging from 0 to 52, higher scores indicate higher severity of depressive symptoms and scores 0-7 are considered as being normal) at endpoint
次要结局
- Depressive symptom profiles (IDS-SR)(T0 -> T6 (12 weeks))
- Therapy compliance (MARS)(T0 -> T6 (12 weeks))
- Adverse effects(T0 -> T6 (12 weeks))
- Change in depressive symptom severity (IDS-30SR)(T0 -> T6 (12 weeks))
- Change in night-time sleep (PSQI)(T0 -> T6 (12 weeks))
- Change in anxiety (STAI)(T0 -> T6 (12 weeks))
- Change in core assessment of psychomotor change (CORE)(T0 -> T6 (12 weeks))
- Metabolic blood markers(T0 -> T6 (12 weeks))
- Response rate of depressive symptoms (HDRS-17)(T0 -> T6 (12 weeks))
- Other metabolic measures(T0 -> T6 (12 weeks))
研究者
Manuel Morrens
Professor Doctor
Universiteit Antwerpen