Role of the noradrenergic system in the regulation of learning dynamics: evaluation of the effect of a low-dose selective noradrenaline reuptake inhibitor (NOISYXETINE)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Participant type

Healthy volunteers

Age range

18-64 years

Gender

Male and Female

Therapeutic area

Psychiatry and Psychology [F] - Psychological Phenomena [F02]

Trial duration

18 Nov 2025 → ongoing

Decision date (initial)

2025-06-26

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

ERC funding (CEA; NEURAL-PROB, Starting Grant 947105) and INM Basic research starting package

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To characterize the role of the noradrenergic system in the regulation of learning dynamics in healthy subjects, by comparing the behaviour of the subject during learning (in a stable accumulation task and in a changing accumulation task), their pupil diameter, and their electroencephalographic (EEG) responses, after taking a single dose of atomoxetine (40 mg) and placebo

Secondary objectives 4

1. To determine the cerebral and pupillary correlates of latent computational variables during the task
2. To check the effect of the atomoxetine on participants’ emotional state (depression, anxiety)
3. To assess tolerance of the IMPs
4. To explore genetic basis of individual differences in learning rate

Conditions and MedDRA coding

Healthy subjects with no neurological or psychiatric disorders

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Age 18 to 39 years old
2. Right-handed, assessed by the Edinburgh scale
3. Written signed informed consent
4. Subject covered by the social security system

Exclusion criteria 13

1. Pregnant, parturient or breastfeeding woman
2. First-degree family history of axis I disorder (DSM-IV-TR), excepted unipolar mood and anxiety disorders with OCD
3. Personal history of axis I disorder (DSM-IV-TR) in the 6 months preceding the study entry
4. 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
5. Neuro/psychotropic treatment ongoing or stopped less than 1 month ago
6. 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.)
7. 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
8. Any medical treatment in the month preceding the study entry, apart from effective contraceptive treatment
9. Subject deprived of liberty by a judicial or administrative decision
10. Person subject to a legal protection measure or unable to express consent
11. Known intolerance to atomoxetine
12. Need to wear glasses and/or lenses to obtain normal vision
13. Subject in an exclusion period or enrolled in an interventional study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary evaluation criterion is the paired difference in the parameters of the computational models that characterize the learning process (in a stable accumulation task and in a dynamic accumulation task), between the sNRI (atomoxetine) and control (placebo) conditions

Secondary endpoints 7

1. Continued EEG recording during the neuropsychological tests at V1 and V2, and its correlation with different latent variables of the learning process, between the atomoxetine and placebo conditions
2. Paired differences in the pupil diameter recorded using an eye-tracking device, and its correlation with different latent variables of the learning process, between the atomoxetine and placebo conditions
3. Paired differences in ECG, and its correlation with different latent variables of the learning process, between the atomoxetine and placebo conditions during the neuropsychological tests
4. Paired difference in salivary cortisol concentration as an indirect marker of noradrenaline function between the atomoxetine and placebo condition
5. Psychometric scales at the end of the neuropsychological tests at V1 and V2: • State Trait Anxiety Inventory (STAI) - to measure anxiety levels, • Beck Depression Inventory (BDI) - to measure the level of depression (Beck et al., 1996), • Visual Analog Scales (VAS) for intensity of anxiety, sadness and fatigue
6. Side effects in all groups between study drug administration (D0) and V2 including vital signs worsening and ECG findings
7. Genotyping for 3 SNPs in genes assumed to affect noradrenergic function: ADRA2 (rs1800544) and two of the NET (rs28386840, rs2242446)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Sponsor organisation

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Address

1 Rue Cabanis

City

Paris

Postcode

75014

Country

France

Scientific contact point

Organisation

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Contact name

Dr Florent MEYNIEL

Public contact point

Organisation

Groupe Hospitalier Universitaire Paris Psychiatrie Et Neuroscience

Contact name

Marin CHAPELLE

Locations

1 EU/EEA country · 1 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 10 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications