Prediction of the Therapeutic Response in Depression Based on an Early Neuro-computational Modeling Assessment of Motivation
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 136
- 试验地点
- 10
- 主要终点
- Prediction of the therapeutic response (MADRS score) 28 days after the introduction of the antidepressant strategy (V3) based on the early changes (differences between V1 and V2) of the computational phenotype of depressed patients.
研究概览
简要总结
This study aims to better understand the mechanisms of action of antidepressants, but also the neural correlates of motivation deficits. One hundred patients with a moderate to severe major depressive episode will be enrolled in this prospective multicenter study. The objective will be to predict the therapeutic response to two first-line antidepressants on the basis of an early neurocomputational assessment of motivation. Antidepressant treatment will be administered as monotherapy after randomization between two drugs: escitalopram and vortioxetine. Patients will undergo six visits and follow-up for one year. The investigators will combine computer modeling and functional MRI to identify motivational deficits and elucidate their brain correlates before initiation, after 7 days and after 6 months of treatment. 36 healthy volunteers will also be included to allow comparison with patients with depression. They will not receive any treatment.
详细描述
One hundred patients with a moderate to severe major depressive episode will be enrolled in this prospective multicenter study. Six visits will be scheduled within a year:
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V0 (inclusion visit): verification of inclusion and exclusion criteria, information, and consent.
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V1 (before randomization - baseline state):
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Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.
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Neuro-cognitive evaluation using a battery of tests to explore motivation, emotion processing, belief construction, and their updating. Part of the tests will be performed during the functional MRI session.
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Structural (anatomical) and functional MRI, ASL.
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Blood samples.
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Randomization and introduction of the new antidepressant will occur immediately after V1. To maximize acceptability by referring psychiatrists, dosage and co-prescriptions will be at the discretion of the psychiatrist in charge, but the assigned treatment will not be changed for 4 weeks (until V3).
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V2 (7 days after the beginning of the new antidepressant - 'early response visit'):
o Similar to V1.
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V3 (28 days after the beginning of the new antidepressant - 'conventional response visit'):
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Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.
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Blood samples
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V4 (6 months after the beginning of the new antidepressant - 'remission visit'):
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Patients with major depressive disorder
- •Inclusion Criteria:
- •Meeting DSM-5 criteria for major depressive disorder (single or recurrent episodes)
- •With a MADRS score >= 24
- •For which a new line of treatment is needed
- •No previous line of antidepressant for this episode or wash-out long-enough to avoid carry-over effects
- •Valid health care insurance
排除标准
- •Treatment-resistant depression (defined as insufficient response despite at least 2 trials of antidepressant prescribed at adequate dose and duration)
- •Subjects with a trial of escitalopram and/or vortioxetine for the current episode, or with contra-indication to one of these two drugs
- •Subjects with a diagnostic of persistent depressive disorder, bipolar disorder or schizophrenia, neurodeveloppemental disorder, unremitted substance abuse disorder other than tobacco, personality disorder severe enough to compromise the follow-up (based on investigator's appreciation).
- •Subject with a history of neurological disorder: parkinson's disease, dementia
- •Contraindications to MRI scanning: pregnancy, claustrophobia, metallic implants
- •Pregnant or breastfeeding women
- •involuntary hospitalisation and legal protection measures
- •Healthy volunteers
- •Inclusion Criteria:
- •- Valid health care insurance
- •Exclusion Criteria:
- •Subjects with a diagnostic of persistent depressive disorder, bipolar disorder or schizophrenia, neurodeveloppemental disorder, unremitted substance abuse disorder other than tobacco, personality disorder severe enough to compromise the follow-up (based on investigator's appreciation).
- •Subject with a history of neurological disorder: parkinson's disease, dementia
- •Contraindications to MRI scanning: pregnancy, claustrophobia, metallic implants
- •Pregnant or breastfeeding women
结局指标
主要结局
Prediction of the therapeutic response (MADRS score) 28 days after the introduction of the antidepressant strategy (V3) based on the early changes (differences between V1 and V2) of the computational phenotype of depressed patients.
时间窗: Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant)
The therapeutic response will be measured with the Montgomery-Asberg Depression Rating Scale (MADRS). The MADRS is a 10- item scale widely used in depression research to assess the severity of depression. Response will be defined by a score divided by 2 compared to baseline MADRS score, while remission will be defined by a score \< 7 (symptom absent) 28 days after the initiation of the antidepressant strategy. The "computational phenotype" is the outcome of the computationnal analysis of behavior. It is expressed in abstract unit. The change in computationnal phenotype between V1 and V2 will be entered in logistic regression aiming to predict clinical response at 28 days, measured with the MADRS score.
次要结局
- Prediction of long-term remission (V4) based on the early changes (differences between V1 and V2) of the neuro-computationnal phenotype of depressed patients(Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant), V4 (6 months after the start of antidepressant))
- Prediction of relapse at one year (V5) based on the computationnal phenotype of remitted patients at 6 months (V4).(V4 (6 months after the start of antidepressant), V5 (1 year after the start of antidepressant))
- Prediction functional remission (V5) based on the early changes (differences between V1 and V2) of the neuro-computationnal phenotype of depressed patients(Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant), V5 (1 year after the start of antidepressant))
- Description of the neural correlates of motivation deficits of depressed patients at baseline (V1).(Baseline state (before the start of antidepressant strategy))
- Description of the evolution of the neural correlates of motivation deficits after one week of antidepressant treatment(Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant))
- Description of the evolution of the structural neural correlates of depression after 6 months of treatment(Baseline state (before the start of antidepressant strategy), V4 (6 months after the start of antidepressant))
- Prediction of the therapeutic response (MADRS score) 28 days after the introduction of the antidepressant strategy (V3) based on the initial (baseline state- V1) neuro-computational phenotype of depressed patients(Baseline state (before the start of antidepressant strategy), and V3 (after 28 days of antidepressant))
- Prediction of the therapeutic response (MADRS score) 28 days after the introduction of the antidepressant strategy (V3) based on the early changes (differences between V1 and V2) of the neuro-computational phenotype of depressed patients(Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant))
- Description of the motivational deficit of depressed patients at baseline (V1).(Baseline state (before the start of antidepressant strategy))
- Description of the evolution of motivation deficit of depressed patients after one week of antidepressant treatment(Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant))
- Description of the evolution of motivation deficit of depressed patients at 6 months(Baseline state (before the start of antidepressant strategy), V4 (6 months after the start of antidepressant))
- Description of the evolution of the functional neural correlates of depression after 6 months of treatment(Baseline state (before the start of antidepressant strategy) V4 (6 months after the start of antidepressant))
- Construction of a bio-bank(Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant), V4 (6 months after the start of antidepressant))