Prediction of the Therapeutic Response in Depression Based on Neuro-computational Modeling Assessment of Motivation

NCT05866575 | Recruiting

• 1 other identifier: D20-P059
• Study Type: interventional
• Target: 136
• Locations: 1 country
• Sites: 5

Brief Summary

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.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• 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.

  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.

  Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant)

Secondary Outcomes (13)

• 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)

• 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 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 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)

• 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)

Study Arms (2)

escitalopram strategy

OTHER

The strategy will not be modified for a period of 4 weeks. Dosage adjustment and co-prescriptions will be at the discretion of the refeering psychiatrist.

Other: escitalopram

vortioxetine strategy

OTHER

The strategy will not be modified for a period of 4 weeks. Dosage adjustment and co-prescriptions will be at the discretion of the refeering psychiatrist.

Other: vortioxetine

Interventions

escitalopram OTHER

Patients will receive an antidepressant strategy : escitalopram. The strategy will not be modified for a period of 4 weeks. Dosage adjustment and co-prescriptions will be at the discretion of the refeering psychiatrist. After 4 weeks, the strategy can be adapted by the refeering psychiatrist exactly as if the patient had not been included in the trial.

escitalopram strategy

vortioxetine OTHER

Patients will receive an antidepressant strategy : vortioxetine. The strategy will not be modified for a period of 4 weeks. Dosage adjustment and co-prescriptions will be at the discretion of the refeering psychiatrist. After 4 weeks, the treatment strategy can be adapted by the refeering psychiatrist exactly as if the patient had not been included in the trial.

vortioxetine strategy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• \- Valid health care insurance
• 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

Sponsors & Collaborators

• Centre Hospitalier St Anne: lead

Study Sites (5)

Groupe hospitalo-universitaire de Grenoble Alpes

La Tronche, Isère, 38700, France

NOT YET RECRUITING

Centre hospitalier Universitaire de Lille

Lille, Nord, 59000, France

NOT YET RECRUITING

Centre hospitalier Universitaire de Saint-Etienne

Saint-Priest-en-Jarez, Pays de la Loire Region, 42270, France

NOT YET RECRUITING

Groupe hospitalo-universitaire Assistance Publique, hôpital Pitié Salpêtrière - Hôpitaux de Paris Sorbonne Université

Paris, 75013, France

NOT YET RECRUITING

- Groupe hospitalo-universitaire Paris Psychiatrie et Neurosciences

Paris, 75014, France

RECRUITING

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MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Escitalopram; Vortioxetine

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Propylamines; Amines; Organic Chemicals; Nitriles; Benzofurans; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Piperazines; Heterocyclic Compounds, 1-Ring

Central Study Contacts

Fabien Vinckier

CONTACT

0033683714083; f.vinckier@ghu-paris.fr

Claire Jaffré

CONTACT

0033650557373; claire.jaffre@yahoo.fr

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Randomization and introduction of the new antidepressant will occur immediately after V1. Patients will receive an antidepressant as monotherapy after randomization between two strategies: escitalopram and vortioxetine. To maximize acceptability by referring psychiatrists, dosage and co-prescriptions will be at the discretion of the psychiatrist in charge, but the allocated treatment will not be changed for 4 weeks (until V3). After 4 weeks, the treatment can be adapted by the refeering psychiatrist exactly as if the patient had not been included in the trial.

Study Record Dates

• First Submitted: November 15, 2022
• First Posted: May 19, 2023
• Study Start: September 12, 2023
• Primary Completion (Estimated): October 12, 2026
• Study Completion (Estimated): November 12, 2026
• Last Updated: July 10, 2024

Record last verified: 2024-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: The data obtained from medical visits (clinical informations, biological assessments, neurocognitive data)and brain MRIs will be kept, coded and archived for a period of two years after the last publication of the research results or until the final research report is signed.
• Access Criteria: The data can be used for collaborative research (academic and/or industrial partners) in the European Union (EU) and/or abroad exclusively for scientific purposes. In case of transfer of the anonymized database resulting from this research abroad (outside the EU), the sponsor undertakes to ensure a level of security equivalent to French or European Union law.

Locations

FR (5)