Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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:
Hundred and sixty healthy volunteers will be enrolled (80 / task) in 24 months. The maximum duration of participation for each subject is 51 days.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Sequence 1: Atomoxetine 40 mg - Placebo | Other | The participants will receive one cap of atomoxetine 40 mg at V1 and placebo at V2 |
|
| Sequence 2: Placebo - Atomoxetine 40 mg | Other | The participants will receive one cap of placebo at V1 and atomoxetine 40 mg at V2 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Atomoxetine | Drug | One single capsule of atomoxetine 40 mg given at one visit according to the sequence randomly allocated. Placebo of atomoxetine will be administered at the other visit for the participant (according to the sequence randomly allocated) |
| Measure | Description | Time Frame |
|---|---|---|
| Apparent Learning rate | 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. | From Visit 1 (Day 0) to Visit 2 (Day 7) |
| Measure | Description | Time Frame |
|---|---|---|
| Number of adverse events | Side effects (treatment related adverse events) in all groups between study drug administration at Visit 1 (Day 0) and Visit 2 (Day 7) including vital signs worsening and ECG findings | 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) |
Not provided
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Florent Meyniel, MD, PhD | Contact | +33 1 45 65 63 90 | florent.meyniel@ghu-paris.fr |
Not provided
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Institut de Neuromodulation | Recruiting | Paris | 75014 | France |
Not provided
Not provided
Not provided
Not provided
Single centre, double-blinded, randomized, placebo-controlled, cross-over study involving 160 evaluable healthy adults. Subjects will be separated in 2 cohorts: A for participants having the stable task and B for those having the changing one. They will then be randomized in a 1:1 ratio to one of the 2 treatment sequences:
Not provided
Not provided
Not provided
| Placebo | Drug | One single capsule of placebo given at one visit according to the sequence randomly allocated. |
|
Computational modelling of behaviour at Visit 1 and 2: paired difference in latent behavioral 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. |
| 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 | The scores of the State Trait Anxiety Inventory (STAI) questionnaire (Spielberger et al., 1983) will be compared between Hour 0 and Hour 3 at Visit 1 and 2 to control for the effect of the substance on the subjects' levels of depression and anxiety. The STAI comprises 2 questionnaires of 20 items with the following ranges:
| 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 | The scores of the Beck Depression Inventory (BDI) questionnaire (Beck et al., 1961) will be compared between Hour 0 and Hour 3 at Visit 1 and Visit 2 to control for the effect of the substance on the subjects' levels of depression. The BDI comprises 21 items with the following ranges: 0-63 with 0 equivalent to no depression and 63 the worst possible depression. | 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 | The scores of the VAS-anxiety will be compared between Hour 0 and Hour 3 at Visit 1 and Visit 2 to control for the effect of the substance on the subjects' levels of anxiety. The VAS ranges from 0 (no anxiety) to 100 mm (worst possible anxiety). | 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 | The scores of the VAS-sadness will be compared between Hour 0 and Hour 3 at Visit 1 and Visit 2 to control for the effect of the substance on the subjects' levels of sadness. The VAS ranges from 0 (no sadness) to 100 mm (worst possible sadness). | 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 | The scores of the VAS-fatigue will be compared between Hour 0 and Hour 3 at Visit 1 and Visit 2 to control for the effect of the substance on the subjects' levels of fatigue. The VAS ranges from 0 (no fatigue) to 100 mm (maximum imaginable fatigue). | From Visit 1 (Day 0) to Visit 2 (Day 7) |
| ID | Term |
|---|---|
| D000069445 | Atomoxetine Hydrochloride |
| ID | Term |
|---|---|
| D011437 | Propylamines |
| D000588 | Amines |
| D009930 | Organic Chemicals |
Not provided
Not provided