Cerebral neuroinflammation during major depressive episode: multicentric comparative study (InflaDep)
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 4
- 主要终点
- TSPO density assessed by the cerebral distribution volume of the tracer [18F]DPA-714 in the experimental group versus the control group.
研究概览
简要总结
The primary outcome is to compare TEP data (i.e. distribution pattern of neuroinflammation) between patients with MDD (experimental group), patients who have had a MDD and being in remission for at least 8 weeks, still treated with antidepressants, matched in age and gender with the experimental group (pathological control group) and control subjects, matched in gender and age with both patients’ groups (control group).
详细描述
The most widespread pathophysiological hypothesis in major depressive disorder (MDD), is the hypothesis of monoamine deficit. The most used antidepressants in everyday clinical practice act by inhibiting the reuptake of monoamines. However, meta-analyzes evaluating the efficacy of antidepressants suggest that they are ineffective in 30 to 40% of patients. Inflammatory mechanisms might be related to the deficiency of monoamines, compromising the effectiveness of conventional antidepressants. Newly developed specific radiotracers allow the use of positron emission tomography (PET) imaging techniques to evaluate neuroinflammation. It has recently demonstrated the relevance of the [18F] DPA- 714 as a biomarker of neuroinflammation in humans in several neurological diseases.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Diagnostic
- 盲法
- None
盲法说明
Images' analysis will be done by an INSERM engineer without the knowledge of the group to which the subjects belong.
入排标准
- 年龄范围
- 18 years 至 64 years（18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •Male or female / age between 18 and 60 years
- •for the pathological control group : Treated with antidepressants (unchanged dosage for at least week)
- •for the control group : Without any neurological or psychiatric previous disorder
- •for the control group : CRPus < 5mg/L
- •Written agreement for participation
- •Able to understand instructions and information data
- •for the experimental group: Responding to MDD criteria (DSM-5)
- •for the experimental group: MADRS score> 20
- •for the experimental group: Antidepressant medication considered ineffective and before the introduction of a new treatment according to the recommendations (unchanged dosage for at least 2 week and plasma levels above the lower end of the therapeutic range done after one week more with unchanged dosage).
- •for the pathological control group : Having met MDD criteria (DSM-5)
- •for the pathological control group : In remission for 8 weeks according to the DSM-5
- •for the pathological control group : MADRS score <10
排除标准
- •Patients without public insurance regime.
- •Specific contraindication to the use of MRI (metallic material) or PET (specific allergy related to the ligand).
- •Pregnant and breastfeeding women
- •Persons deprived of liberty by judicial or administrative decision
- •People hospitalized without consent, or subject to legal protection
- •Persons unable to consent
- •Patients with a neurodegenerative disease, bipolar disease, chronic psychotic disorder, addictive disorder, Obsessive Compulsive Disorder, Post-Traumatic Stress disorder, known system pathology
- •Patients with a history of stroke
- •Patients with an acute infectious disease
- •Persons with a phenotype of low affinity to the TSPO tracer
- •Patients with chronic inflammatory pathology.
- •Patients treated with anti-inflammatory and/or immunosuppressive, and/or antipsychotics, and/or benzodiazepine
- •History of documented head trauma
- •for control group: No significant psychiatric or somatic history.
- •for control group: No psychotropic treatment
- •for control group: Suicidal risk (C-SSRS)
- •for control group: Anxiety Disorders (MINI)
结局指标
主要结局
TSPO density assessed by the cerebral distribution volume of the tracer [18F]DPA-714 in the experimental group versus the control group.
TSPO density assessed by the cerebral distribution volume of the tracer [18F]DPA-714 in the experimental group versus the control group.
次要结局
- the density of the TSPO evaluated by the cerebral distribution volume of the tracer [18F]DPA-714 in the 3 groups (experimental, control and pathological control).
- psychometric scales making it possible to assess the clinical state of subjects: o Depression scale (MADRS) o Anhedonia Scale (SHAPS) o Psychomotor slowing scale (Widlocher scale) o Suicide Risk Rating Scale (CSSRS) o BAS Anxiety Rating Scale (Brief Scale for Anxiety)
- imagery markers o by structural MRI (i.e. the cortical thickness allowing the quantification of cortical atrophy) o diffusion (i.e. the average diffusivity allowing microstructural integrity to be measured) o T2* relaxometry (i.e. R2* to measure intracerebral iron content) o Resting functional MRI (i.e. connectivity strength of the default mode network)
- concentrations of biological markers of peripheral inflammation (TNF alpha and IL6)
- Proteomics: identification of plasma proteins and relative quantification of their abundances
研究者
Dr Antoine YRONDI
Scientific
Centre Hospitalier Universitaire De Toulouse