A Clinical Biomarker Study of Immunological Phenotypes Associated With Monoaminergic Anti-depressant Response, and the Brain and Cognitive Phenotypes Associated With Variation in Peripheral C-reactive Protein (CRP) Levels, in Patients With Major Depressive Disorder (MDD).
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 393
- 试验地点
- 5
- 主要终点
- C-reactive protein (CRP) levels (mg/l)
研究概览
简要总结
This is a study to characterise the role of inflammatory processes in depression. There is compelling evidence that inflammation is often associated with, and can cause, depression. It is currently less clear that antiinflammatory drugs have meaningful antidepressant effect. One of the goals is to identify the subset of depressed patients that is most likely to respond better to an antiinflammatory drug than to a conventional antidepressant. The investigators will therefore undertake a study of patients with a diagnosis of major depressive disorder including four groups: i) incompletely responsive patients who have demonstrated failure to respond consistently or completely to standard treatment, ii) those who have responded well to treatment and are not currently depressed, iii) untreated patients who are currently depressed, iv) healthy volunteers with no history of depression. Participants will undergo a clinical assessment, an interview with a trained member of the research team and will complete self-rated questionnaires. Investigators will collect blood and saliva samples to measure certain immune markers. They will also perform magnetic resonance imaging (MRI) scans to look for MRI markers in the brain and investigate brain inflammation in a subsample of these patients using positron emission topography (PET) and cerebrospinal fluid (CSF) sampling (also called lumbar puncture).
详细描述
The hypotheses are (i) that therapeutic resistance to monoaminergic (MA) antidepressant drugs is associated with peripheral biomarkers indicating abnormal activation of the innate immune system; and (ii) that peripheral inflammation, defined by blood levels of C-reactive protein (CRP), is associated with central nervous system inflammation and abnormal brain structure and function.
The objectives are to test these two hypotheses by collecting clinical, immunological and neuroimaging data on patients with depression (DEP+) recruited from a network of clinical research sites in the United Kingdom.
Primary objective:
To measure peripheral immunophenotypes in healthy volunteers (at least N=50) and 3 groups of depressed patients, categorised by their exposure and therapeutic response to monoaminergic antidepressants (up to N=200):
- Incompletely responsive patients (approximately N ~100) who are currently depressed after greater than 6 weeks of treatment with one or more monoaminergic antidepressants (DEP+MA+);
- Responsive patients (approximately N~50) who are not currently depressed after greater than 6 weeks of treatment with a monoaminergic antidepressant (DEP-MA+);
- Untreated patients (approximately N~50) who are currently depressed but have not been treated with monoaminergic antidepressants in the previous 6 weeks (DEP+MA-);
- Healthy volunteers (approximately N~50) who have no personal history of depression requiring treatment with either monoaminergic antidepressants or other clinical interventions including psychotherapy (DEP-MA-).
研究设计
- 研究类型
- Observational
- 观察模型
- Case Control
- 时间视角
- Prospective
入排标准
- 年龄范围
- 25 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Major depressive disorder diagnosed by structured clinical interview in accordance with Diagnostic and Statistical Manual of Mental Disorders (DSM) criteria
- •Aged 25-50 years inclusive
- •HAM-D score at baseline
- •DEP+MA+ subgroup > 13
- •DEP+MA- subgroup > 17
- •DEP-MA+ subgroup < 7
- •Able and willing to give informed consent, including consent to sharing of clinical information with the participant's general practitioner
- •Willing to abstain from strenuous exercise for 72 hours prior to assessment
- •Able to write, speak and understand English
排除标准
- •Life time history of bipolar disorder or nonaffective psychosis
- •Concurrent medication likely to compromise the interpretation of immunological data (including, but not limited to corticosteroids, or any other substance to be determined by the Principal Investigator or delegate)
- •Pregnancy or breast feeding
- •Active alcohol or drug abuse or dependence in the last 6 months
- •Participation in clinical trial of an investigational drug within the last 12 months
- •Lifetime history of any serious medical disorder likely to compromise the interpretation of immunological data (including, but not limited to, immunological disorders, cardiovascular disorders, malignancies or infection, or any other condition to be determined by the Principal Investigator or delegate)
结局指标
主要结局
C-reactive protein (CRP) levels (mg/l)
时间窗: One year after last participant visit
Flow cytometric immunophenotype
时间窗: One year after last participant visit
The exact antibody panel will be developed during the research study
次要结局
- Structural parameters of the brain(One year after last participant visit)
- Microglial activation in the brain(One year after last participant visit)
- Response to stimulus(One year after last participant visit)
- Pro-inflammatory (M1-like) phenotype-producing cytokines, such as interleukin (IL)-1, IL-6, and tumor necrosis factor (TNF)-α circulating in cerebrospinal fluid(One year after last participant visit)
研究者
Linda Pointon
Professor Edward T. Bullmore
University of Cambridge