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

Major Depressive Disorder Clinical Trial

— STRATIDEP  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05866575
• Other study ID #: D20-P059
• Status: Not yet recruiting
• Phase: N/A
• Start date: June 1, 2023
• Est. completion date: December 31, 2026

Study information

• Verified date: May 2022
• Source: Centre Hospitalier St Anne
• Contact: Fabien Vinckier
• Phone: 0033683714083
• Email: f.vinckier[@]ghu-paris.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

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:

• V0 (inclusion visit): verification of inclusion and exclusion criteria, information, and consent.

• V1 (before randomization - baseline state):

• Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.

• 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.

• Structural (anatomical) and functional MRI, ASL.

• Blood samples.

• 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).

• V2 (7 days after the beginning of the new antidepressant - 'early response visit'):

o Similar to V1.

• V3 (28 days after the beginning of the new antidepressant - 'conventional response visit'):

• Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.

• Blood samples

• V4 (6 months after the beginning of the new antidepressant - 'remission visit'):

• Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.

• Cognitive evaluation using a battery of tests to explore motivation, emotion processing, belief construction, and their updating.

• Structural (anatomical) MRI, ASL

• Blood samples

• V5 (one year after the beginning of the new antidepressant - 'functional remission visit'):

• Clinical evaluation using validated questionnaires for the severity of depression, quality of life, anhedonia, apathy, and cognitive dysfunction.

36 healthy volunteers without a history of neurologic or psychiatric disorder, matched for age, gender, and education will be included. They will perform V0-V2 (without MRI and blood sample at V2). Healthy volunteers will not receive any treatment as part of the research.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 136
• Est. completion date: December 31, 2026
• Est. primary completion date: November 1, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Exclusion Criteria:

• 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

Related Conditions & MeSH terms

• Depressive Disorder
• Depressive Disorder, Major
• Major Depressive Disorder

Intervention

Other:
• escitalopram
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.
• vortioxetine
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.

Locations

Country	Name	City	State
France	Groupe hospitalo-universitaire de Grenoble Alpes	La Tronche	Isère
France	Centre hospitalier Universitaire de Lille	Lille	Nord
France	- Groupe hospitalo-universitaire Paris Psychiatrie et Neurosciences	Paris
France	Groupe hospitalo-universitaire Assistance Publique, hôpital Pitié Salpêtrière - Hôpitaux de Paris Sorbonne Université	Paris
France	Centre hospitalier Universitaire de Saint-Etienne	Saint-Priest-en-Jarez	Loire

Sponsors (1)

Lead Sponsor	Collaborator
Centre Hospitalier St Anne

Country where clinical trial is conducted

France, 

References & Publications (57)

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* Note: There are 57 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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	Same than outcome 1 but using brain imaging on top of behavior (neurocomputational modeling) to predict clinical response.	Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant) and V3 (after 28 days of antidepressant)
Secondary	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	Same than Outcome 2 but using only V1 instead of the change between V1 and V2 to predict clinical response.	Baseline state (before the start of antidepressant strategy), and V3 (after 28 days of antidepressant)
Secondary	Prediction of long-term remission (V4) based on the early changes (differences between V1 and V2) of the neuro-computationnal phenotype of depressed patients	Same than Outcome 2 but to predict clinical remission at V4 instead of clinical response at V3.	Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant), V4 (6 months after the start of antidepressant)
Secondary	Prediction functional remission (V5) based on the early changes (differences between V1 and V2) of the neuro-computationnal phenotype of depressed patients	Same than Outcome 2 but to predict functional remission at V5 instead of clinical response at V3.	Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant), V5 (1 year after the start of antidepressant)
Secondary	Prediction of relapse at one year (V5) based on the computationnal phenotype of remitted patients at 6 months (V4).	Same than Outcome 1 but using computational phenotype at V4 to predict predict functional remission at V5.	V4 (6 months after the start of antidepressant), V5 (1 year after the start of antidepressant)
Secondary	Description of the motivational deficit of depressed patients at baseline (V1).	Comparison of the computational phenotype of patients with depression and healthy volunteers at V1.	Baseline state (before the start of antidepressant strategy)
Secondary	Description of the neural correlates of motivation deficits of depressed patients at baseline (V1).	Comparison of the brain functional statistical maps of patient with depression and healthy volunteers at V1.	Baseline state (before the start of antidepressant strategy)
Secondary	Description of the evolution of motivation deficit of depressed patients after one week of antidepressant treatment	Comparison of the computational phenotype of patients with depression at V1 and V2.	Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant)
Secondary	Description of the evolution of the neural correlates of motivation deficits after one week of antidepressant treatment	Comparison of the brain functional statistical maps of patient with depression at V1 and V2.	Baseline state (before the start of antidepressant strategy), V2 (after 7 days of antidepressant)
Secondary	Description of the evolution of motivation deficit of depressed patients at 6 months	Comparison of the computational phenotype of patients with depression at V1 and V4.	Baseline state (before the start of antidepressant strategy), V4 (6 months after the start of antidepressant)
Secondary	Description of the evolution of the structural neural correlates of depression after 6 months of treatment	Comparison of the structural brain imaging of patients with depression at V1 and V4.	Baseline state (before the start of antidepressant strategy), V4 (6 months after the start of antidepressant)
Secondary	Description of the evolution of the functional neural correlates of depression after 6 months of treatment	Comparison of the function brain imaging (ASL) of patients with depression at V1 and V4.	Baseline state (before the start of antidepressant strategy) V4 (6 months after the start of antidepressant)
Secondary	Construction of a bio-bank	Serum tubes will be drowned along the study (V1, V2, V3 and V4 for patients - V1 for healthy volunteers) prepared and stored.	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)