Role of the Noradrenergic System in the Regulation of Learning Dynamics: Evaluation of the Effect of a Low-dose Selective Noradrenaline Reuptake Inhibitor (NOISYXETINE)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 160
- 试验地点
- 1
- 主要终点
- Apparent Learning rate
研究概览
简要总结
Administration of low-dose selective noradrenaline reuptake inhibitor (sNRI) (e.g. atomoxetine) to healthy subjects is a validated model of increasing cortical noradrenaline levels which, combined with computational modelling of behaviour, allows fine-grained analysis of the impact on learning processes of noradrenaline's fluctuations in the human cortex.
The study goal is to characterize the modifications of certain cognitive processes and associated brain circuits under low-dose sNRI using validated computational learning models. The study will be interested in how subjects will modify their learning under the effect of the drug across two separate investigations; one utilizing in a stable evidence accumulation task and one utilising a changing evidence accumulation task. This approach will help to better understand the link between noradrenaline and accumulation of evidence in healthy subjects, and indirectly in some neuropsychiatric pathologies.
The study is a single centre, double-blinded, randomized, placebo-controlled, cross-over study involving evaluable healthy adults separated in 2 cohorts: A for participants having the stable task and B for those having the changing one. Participants will then be randomized in a 1:1 ratio to one of the following treatment sequences:
- Atomoxetine 40 mg - Placebo (Subgroups A1 or B1);
- Placebo - Atomoxetine 40 mg (Subgroups A2 or B2).
详细描述
Hundred and sixty healthy volunteers will be enrolled (80 / task) in 24 months. The maximum duration of participation for each subject is 51 days.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 39 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Right-handed, assessed by the Edinburgh scale;
- •Written signed informed consent;
- •Subject covered by a social security regimen.
排除标准
- •Pregnant, parturient or breastfeeding woman;
- •First-degree family history of axis I disorder (DSM-IV-TR), excepted unipolar mood and anxiety disorders with OCD;
- •Personal history of axis I disorder (DSM-IV-TR) in the 6 months preceding the study entry;
- •Dependence on a psychoactive substance in the 12 months preceding the study entry, excluding nicotine, any behavioural disorder incompatible with a 2-hour electroencephalographic recording;
- •Neuro/psychotropic treatment ongoing or stopped less than 1 month ago;
- •Personal history of neurological pathology (e.g.: congenital malformation, benign or malignant tumour, degenerative disease of the central nervous system (CNS), epilepsy, inflammatory or infectious disease of the CNS, etc.);
- •Personal history of chronic disease of infectious, neoplastic, vascular, dysimmune or inflammatory, metabolic or endocrine, degenerative or genetic aetiology. In particular, angle-closure glaucoma, pheochromocytoma, known high blood pressure or measured blood pressure greater than 140/90 mm Hg at baseline, congenital heart disease, known ischemic heart disease, known heart failure, supraventricular or ventricular heart rhythm disorder, nephropathy, known liver disease and any pathology likely to be aggravated by an increase in blood pressure;
- •Any medical treatment in the month preceding the study entry, apart from effective contraceptive treatment;
- •Subject deprived of liberty by a judicial or administrative decision;
- •Person subject to a legal protection measure or unable to express consent;
- •Known intolerance to atomoxetine;
- •Need to wear glasses and/or lenses to obtain normal vision;
- •Subject in an exclusion period or enrolled in an interventional study.
研究组 & 干预措施
Sequence 1: Atomoxetine 40 mg - Placebo
The participants will receive one cap of atomoxetine 40 mg at V1 and placebo at V2
干预措施: Atomoxetine (Drug)
Sequence 1: Atomoxetine 40 mg - Placebo
The participants will receive one cap of atomoxetine 40 mg at V1 and placebo at V2
干预措施: Placebo (Drug)
Sequence 2: Placebo - Atomoxetine 40 mg
The participants will receive one cap of placebo at V1 and atomoxetine 40 mg at V2
干预措施: Atomoxetine (Drug)
Sequence 2: Placebo - Atomoxetine 40 mg
The participants will receive one cap of placebo at V1 and atomoxetine 40 mg at V2
干预措施: Placebo (Drug)
结局指标
主要结局
Apparent Learning rate
时间窗: From Visit 1 (Day 0) to Visit 2 (Day 7)
Paired difference in the apparent learning rates (in both environmental contexts: stable task and changing task), between the sNRI (atomoxetine) and control (placebo) conditions. Apparent learning rate will be calculate with the following formula: αt=(vt- vt-(1) )/(xt- vt-1) according to Foucault and Meyniel (Foucault C, Meyniel F (2024) Two Determinants of Dynamic Adaptive Learning for Magnitudes and Probabilities. Open Mind : Discov Cogn Sci 8:615-638) The learning rate measures the amount of update of the learned value (from vt-(1 to vt) induced by the observation xt in proportion to its deviation from the previously learned value.
次要结局
- Number of adverse events(From Visit 1 (Day 0) to Visit 2 (Day 7))
- Change from Visit 1 (Day 0) in the computational modelling of behaviour at Visit 2 (Day 7)(From Visit 1 (Day 0) to Visit 2 (Day 7))
- Change from Visit 1 (Day 0) in the score of the State Trait Anxiety Inventory (STAI) questionnaire at Visit 2(From Visit 1 (Day 0) to Visit 2 (Day 7))
- Change from Visit 1 (Day 0) in the score of the Beck Depression Inventory (BDI) questionnaire at Visit 2(From Visit 1 (Day 0) to Visit 2 (Day 7))
- Change from Visit 1 (Day 0) in the score of visual analogue scale (VAS) on anxiety at Visit 2(From Visit 1 (Day 0) to Visit 2 (Day 7))
- Change from Visit 1 (Day 0) in the score of visual analogue scale (VAS) on sadness at Visit 2(From Visit 1 (Day 0) to Visit 2 (Day 7))
- Change from Visit 1 (Day 0) in the score of visual analogue scale (VAS) on fatigue at Visit 2(From Visit 1 (Day 0) to Visit 2 (Day 7))